Clinical trial NCT04374019
Conditions: COVID Sars-CoV2
Keywords: high-risk
Sponsor: Susanne Arnold
Start date: 2020-05-01; Completion date: 2022-01-12
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate, artemesia annua. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus replication in will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.

Detailed description:
Coronavirus Disease 2019 (COVID-19) is a highly contagious disease, caused by a novel enveloped RNA beta-coronavirus, also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The first case of this unprecedented outbreak "pneumonia of unknown etiology" was reported in Wuhan City, Hubei Province, China on December 8th, 2019 and reported to the World Health Organization (WHO) on December 31st, 2019. WHO declared a COVID-19 global emergency on January 30, 2020, and then categorized the outbreak as a pandemic on March 11, 2020. As of April 22, 2020, more than 2,628,894 confirmed cases of COVID-19 worldwide and 182,740 people globally have died from COVID-19 since it emerged in China, according to the data from Johns Hopkins University.

While the majority of patients with COVID-19 develop mild or uncomplicated illness, approximately 20-30% of hospitalized patients have required intensive care support and 5% of those have multi-organ failure or shock. The case fatality rate ranges from 1 to 4% and it is higher among those with pre-existing comorbid conditions such as cardiovascular disease, diabetes mellitus, obesity, chronic respiratory disease, hypertension and cancer. The vast majority of patients present with fever (83-99%), cough (59-82%), fatigue (44-70%), anorexia (40-84%), shortness of breath (31-40%), sputum production (28-33%), myalgias (11-35%). Less than 10% of patients will present with headache, confusion, rhinorrhea, sore throat, hemoptysis, vomiting, or diarrhea. Anosmia or ageusia proceeding the onset of respiratory symptoms has been anecdotally reported.

To date, treatments for COVID-19 in high risks individuals remain experimental and therapeutic strategies to deal with the infection are at best supportive, with prevention aimed at reducing transmission in the community as the best weapon. No proven therapies have been demonstrated to prevent the progression of COVID-19 to severe illness and this is a critical unmet need for high-risk individuals and warrants study. Recently, the Infectious Disease Society of America has made recommendations for the treatment of patients with COVID-19, focusing on inpatient care, and recommending randomized trials where possible as the best step to improve treatment outcomes and to increase our understanding of this coronavirus pandemic. Discoveries in this area may inform clinicians on effective treatment for low-risk individuals who progress to severe illness, as well.

Arms: arm 1: Ivermectin arm 2: Camostat Mesilate arm 3: Artemesia annua tea or coffee arm 4: Artesunate
Interventions: intervention 1: Ivermectin intervention 2: Camostat Mesilate intervention 3: Artemesia annua intervention 4: Artesunate
Intervention descriptions: intervention 1: Ivermectin:

Days 1-2: Weight \< 75kg: 4 tabs (12 mg total daily dose) Days 1-2: Weight \> 75kg: 5 tabs (15 mg total daily dose) intervention 2: Days 1-14: 2 tab TID after a meal (600 mg total daily dose) intervention 3: Days 1-14: tea or coffee pod TID (1350 mg total daily dose) intervention 4: Days 1-14:

Protocol documents:
Prot_SAP_000.pdf: 
Study Protocol and Statistical Analysis Plan 
 
 Study Title: Novel Agents for Treatment of High-risk COVID-19 Positive Patients  
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
8/28/2020 
NCT Number: 
NCT04374019 
IRB Number 
58944 
Coversheet created: 
1/12/2022 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n, 
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
A me n d me nt 4 A u g us t 2 8, 2 0 2 0  
i 
M C C Pr ot oc ol #:  
M C C - 2 0-C O VI D - 0 1-P M C  
Cli n ic al Tri als. g o v I de ntifier:  N C T 0 4 3 7 4 0 1 9 3 
TI T L E:    M ulti -ar m p hase II trial f or i nitial assess me nt of n o vel a ge nts f or treat me nt of 
hi g h- ris k C O VI D 1 9 p ositi ve patie nts  
R O L E  
N A M E  
D E P A R T M E N T/ DI VI SI O N  
Pri nci p al 
I n vesti g at ors 
S usa n ne Ar n ol d, M D  
Mar ke y Ca ncer Ce nter, De part me nt of 
I nter nal Me dici ne, Me dical O nc ol o g y 
Ja mes Zac har y  P orterfiel d, M D, P h D   De part me nt of I nter nal Me dici ne, 
Di visi o n of I nfecti o us Diseases 
Jill K olesar, P har m D 
Mar ke y Ca ncer Ce nter, C o -Lea der D T 
Pr o gra m, a n d Pr ofess or, C olle ge of 
P har mac y  
Zi n M yi nt, M D  
Mar ke y Ca ncer Ce nter, De part me nt of 
I nter nal Me dici ne, Me dical O nc ol o g y 
Hei di Weiss, P h D  
Mar ke y Ca ncer Ce nter a n d 
Bi ostatistics a n d Bi oi nf or matics 
S hare d Res o urce Facilit y ( B B S R F), 
De part me nt of I nter nal Me dici ne  
D o n gli n Ya n, P h D  
Mar ke y Ca ncer Ce nter B B S R F, 
De part me nt of I nter nal Me dici ne  
T herese B oc kla ge, M D  
Mar ke y Ca nce r Ce nter Bi os peci me n 
Pr oc ure me nt a n d Tra nslati o nal 
Pat h ol o g y S R F, De part me nt of 
Pat h ol o g y a n d La b orat or y Me dici ne  
Elija h Ka ka ni, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of H os pital Me dici ne  
Jare d Ha m mill, P h D 
C olle ge of P har mac y  
Fra n k R o ma nelli, P har m D  
C olle ge of P har mac y  
Alice T h or nt o n, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of I nfecti o us Diseases  
Sc ott Berr y, P h D  
C olle ge of E n gi neeri n g, De part me nt 
of Mec ha nical E n gi neeri n g  
Aar o n Hessels o n, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of Car di ol o g y  
Pra dee p  Yarra, M D  
De part me nt of I nter nal Me dici ne, 
Di visi o n of H os pital Me dici ne  
C olla b orat ors: 
Re becca D utc h, P h D  
I nteri m C hair, De part me nt of M olec ular 
& Cell ular Bi oc he mistr y  
P hil Ker n, M D  
De part me nt of I nter nal Me dici ne , 
E n d ocri n ol o g y a n d Ass ociate Pr o v ost f or 
Cli nical a n d Tra nslati o nal Scie nces  
Direct or, Ce nter f or Cli nical a n d 
Tra nslati o nal Scie nces  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
ii 
 
 
I n vesti g ati o n al A ge nt(s):  I ver mecti n, ge neric; Ca m ostat  Mesilate ; Arte misia a n n ua, Artes u nate  
 
F u n di n g S o urce:  U ni versit y of Ke nt uc k y C olle ge of Me dici ne 
 
F D A I N D St at us: Ca m ostat Mesilate , I ver mecti n, Arte misia a n n ua, Artes u nate , I N D # 1 5 0 1 0 3  
 
Pr ot oc ol T y pe / Versi o n # / Versi o n D ate:   A me n d me nt / Versi o n 4 / A u g ust 2 8, 2 0 2 0  
  
   
 
C o ns ulta nts  
R o bert Di Pa ola, M D  
Dea n, C olle ge of Me dici ne  
R. Ki p G u y, P h D  
Dea n, C olle ge of P har mac y  
Vi ve k Ra n g ne kar, P h D  
Ass oci at e Dir ect or, M ar k e y C a ncer 
C e nt er a n d Pr ofess or of R a diati o n  
M e dici n e  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
iii 
 
S U M M A R Y O F C H A N G E S  
M C C- 2 0 -C O VI D -P M C  
Pr ot oc ol: Re visi o n, v 4 
Versi o n Date: 1 8 A U G U S T 2 0 2 0  
 
# 
Secti o n  
C o m me nts  
1.  
 C o ver 
pa ge 
A d de d ne w a ge nt na me: Artes u nate, u p date date of re visi o n a n d versi o n n u m ber, 
clarifie d title; re vise d I N D stat us of eac h c o m p o u n d  
2.  
 
Sc he ma  U p date d fi g ure 
3.  
 T O C  
U p date d ta ble of c o nte nts 
4.  
 1. 1  
U p date d pri mar y  e n d p oi nt t o re m o ve refere nce t o h y dr o x yc hl or o q ui ne , clarifie d 
t he pri mar y p ur p ose of t his trial a n d clarifie d t he c ha n ge i n C O VI D- 7-P oi nt scale 
is less t ha n a 2-p oi nt decrease i n sc ore.  
5.  
 2. 4  
Re m o ve d bac k gr o u n d f or h y dr o x yc hl or o q ui ne a n d azit hr o m yci n a n d  u p date d 
secti o n n u m ber f or arte misia a n n ua 
6.  
 2. 5  
A d de d bac k gr o u n d f or artes u nate c o m p o u n d i ncl u di n g cli nical t o xic ol o g y a n d 
p har mac o ki netic e x perie nce  
7.  
 2. 6  
E x pa n de d rati o nale t o i ncl u de use of t he pic k -t he-wi n ne r trial desi g n a n d re m o ve d 
refere nce t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n  a n d a d de d a fi g ure f or t he 
C O VI D - 7 p oi nt or di nal scale a n d pri mar y e n d p oi nt. 
8.  
 3. 2  
Re m o ve d Q Tc e xcl usi o n a n d re m o ve d refere nce s t o h y dr o x yc hl or o q ui ne a n d 
azit hr o m yci n , as n o ne of t he c o m p o u n ds i n t his trial ha ve Q T pr ol o n gati o n. 
Clarifie d c o nc urre nt use d of C Y P 2 A 6 i n d ucers is e xcl u de d f or b ot h arte misia 
a n n ua a n d artes u nate 
9.  
 4. 9  
Clarifie d t he use of r o uti ne e xa mi nati o n, a d de d Da y 3 -4 a n d Da y 1 0 -1 1 safet y 
assess me nt  
1 0.  
 6. 1  
R e m o ve d refere nce t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n  t hr o u g h o ut a n d 
re gi me n descri pti o ns, a n d a d de d Re gi me n F artes u nate descri pti o n. 
Clarifie d t hat all ar ms will ha ve safet y r u n -i ns  
C ha n ge d t he  f oll o wi n g se nte nce: 
N O T E: if a patie nt de vel o ps a m y ocar dial i nfarcti o n or d oc u me nte d Q Tc > 5 0 0 
w hi le o n t he 1 4 da ys of dr u g, t he y s h o ul d be i m me diatel y ta ke n off st u d y 
me dicati o n a n d recei ve sta n dar d of care treat me nt per t heir treati n g p h ysicia n.  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
i v 
 
# 
Secti o n  
C o m me nts  
T o:  
N O T E: if a patie nt de vel o ps a m y ocar dial i nfarcti o n or gra de 3 or 4 car diac 
arr yt h mia or d oc u me nte d Q Tc > 5 0 0 w hile o n t he 1 4 da ys of dr u g, t he y s h o ul d be 
i m me diatel y ta ke n off st u d y me dicati o n a n d recei ve sta n dar d of care treat me nt per 
t heir treati n g p h ysicia n. 
1 1.  
 8. 1  
Re m o ve d refere nce t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n as well as a d verse 
e ve nts listi n gs f or t hese dr u gs a n d a d de d artes u nate a n d its a d verse e ve nts listi n g  
1 2.  
 9. 1  
Clarifie d t hat less t ha n a 2 p oi nt D E C R E A S E i n C O VI D 7 -P OI N T O R DI N A L 
O U T C O M E S S C A L E  is a p ositi ve res ult a n d clarifie d t hat c o m paris o ns bet wee n 
ar ms or wit h a place b o is n ot perf or me d i n t his st u d y desi g n. 
1 3.  
 9. 2  
Clarifie d t he ti me fr o m baseli ne t o i m pr o ve me nt is b ot h Da y 1 4 a n d Da y 2 8  
1 4.  
 9. 3  
Clarifie d t he pri mar y e n d p oi nt a n d g oal of a decrease less t ha n 2 p oi nts i n C O VI D 
7- P OI N T O R DI N A L S C A L E  (cli nical sta bilit y) 
1 5.  
 9. 4  
Re m o ve d all refere nces t o h y dr o x yc hl or o q ui ne a n d azit hr o m yci n a n d clarifie d t he 
ra n d o mizati o n list pr ocess. 
1 6.  
 
9. 5 a n d 
9. 6 
Clarifie d t he defi niti o n of cli nical sta bilit y as a less t ha n 2 p oi nt decrease i n 
C O VI D scale.  
1 7.  
 1 0. 3  
U p date d e x pe dite d A E re p orti n g g ui deli nes  
1 8.  
 1 1  
A d de d p h o ne c o ntacts i n st u d y cale n dar f or Da y 3 or 4 a n d Da y 1 0 or 1 1 a n d 
clarifie d i n-pers o n vers us tele healt h e val uati o ns  
1 9.  
 1 2. 1  
Clarifie d le n gt h of f oll o w-u p  
2 0.  
 
A p p C  
Re m o ve d dr u g diaries f or H y dr o x yc hl or o q ui ne a n d Azit hr o m yci n, c orrecte d 
miss pelli n gs a n d a d de d Dr u g Diar y f or Artes u nate 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
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C O M M O N P R O T O C O L A B B R E VI A TI O N S  
 
A b 
A nti b o d y  
A E 
A d v er s e e v e nt  
A g 
A nti g e n  
A L T  
Al a ni n e tr a n s a mi n a s e t e st; al s o “ S G P T”  
A N C  
A b s ol ut e n e utr o p hil c o u nt  
A R D S  
A c ut e r e s pir at or y di str e s s s y n dr o m e  
A S T 
A s p art at e A mi n otr a n sf er a s e t e st; al s o “ S G O T”  
A U C  
Ar e a u n d er t h e c ur v e  
BI D 
T wi c e a d a y; al s o, “ b.i. d.” , “ bi d”  
B MI 
B o d y m a s s i n d e x  
B P T P S R F  
Bi o s p e ci m e n Pr o c ur e m e nt a n d Tr a n sl ati o n al P at h ol o g y S h ar e d R e s o ur c e F a cilit y  
C B C  
C o m pl et e bl o o d c o u nt; s o m eti m e s s e e n “ wit h diff”, diff er e nti al  
C C T S  
C e nt er f or Cli ni c al a n d Tr a n sl ati o n al S ci e n c e  
C D C  
U. S. C e nt er s f or Di s e a s e C o ntr ol a n d Pr e v e nti o n  
C D M P  
Cli ni c al D at a M o nit ori n g Pl a n  
C F R  
C o d e of F e d er al R e g ul ati o n s  
c m 
C e nti m et er  
C M P  
C o m pr e h e n si v e m et a b oli c p a n el  
C o -I 
C o -i n v e sti g at or 
C O VI D -1 9  
C or o n a vir u s Di s e a s e 2 0 1 9  
C R  
C o m pl et e r e s p o n s e  
C R N/ C R A  
Cli ni c al r e s e ar c h n ur s e / cli ni c al r e s e ar c h a s s o ci at e  ( st u d y st aff) 
C R O  
M ar k e y’ s Cli ni c al R e s e ar c h Or g a ni z ati o n  
C R S O  
Cli ni c al R e s e ar c h S u p p ort Offi c e, U ni v er sit y of K e nt u c k y H e alt h c ar e  
C T  
C o m p ut e d t o m o gr a p h y  
C Y P  
C yt o c hr o m e P 4 5 0  
C Y P 3 A 4 
C yt o c hr o m e P 4 5 0 i s of or m 3 A 4  
D S M C 
D at a a n d  S af e t y M o nit ori n g C o m mitt e e, M ar k e y C a n c er C e nt er 
D S M P 
D at a a n d S af et y M o nit ori n g Pl a n  
e C R F  
El e ctr o ni c c a s e r e p ort f or m ( al s o C R F, c a s e r e p ort f or m)  
E D C  
El e ctr o ni c d at a c a pt ur e s y st e m  
E K G 
El e ctr o c ar di o gr a m t e st  
F D A  
U. S. F o o d a n d Dr u g A d mi ni str ati o n  
G F R  
Gl o m er ul ar filtr ati o n r at e  
HI P A A 
H e alt h I n s ur a n c e P ort a bilit y a n d A c c o u nt a bilit y A ct  
I C H 
I nt er n ati o n al C o u n cil f or H ar m o ni s ati o n of G ui d eli n e s f or G o o d Cli ni c al Pr a cti c e 
I D E 
I n v e sti g ati o n al D e vi c e E x e m pti o n, p er t h e F D A 
I D S 
I n v e sti g ati o n al Dr u g Ser vi c e at U ni v er sit y of K e nt u c k y  
I H C 
I m m u n o hi st o c h e mi str y 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
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S C H E M A  
II T 
I n v e sti g at or-i niti at e d tri al 
I N D 
I n v e sti g ati o n al N e w Dr u g, p er t h e F D A 
I R B 
I n stit uti o n al R e vi e w B o ar d 
I V 
I ntr a v e n o u s dr u g a d mi ni str ati o n  
k g 
Kil o gr a m  
L F T  
Li v er f u n cti o n t e st  
m
2  
S q u ar e m et er  
M A D 
M a xi m u m a d mi ni st er e d d o s e  
M C C  
M ar k e y C a n c er C e nt er  
m c L 
Mi cr olit er  
m g 
Milli gr a m  
m g/ d L  
Milli gr a m s p er d e cilit er  
m g/ k g 
Milli gr a m/ Kil o gr a m  
mi n  
Mi n ut e; al s o “ mi n.”  
ml 
Millilit er  
ml/ mi n  
Millilit er p er mi n ut e  
m m 
Milli m et er  
M T D 
M a xi m u m t ol er at e d d o s e 
N CI  
N ati o n al C a n c er I n stit ut e  
NI H  
N ati o n al I n stit ut e s of H e alt h  
N S AI D 
N o n -st er oi d al a nti -i nfl a m m at or y dr u g 
O S  
O v er all s ur vi v al  
PI 
Pri n ci p al i n v e sti g at or  
P K s 
P h ar m a c o ki n eti c s  
p lt s 
Pl at el et s  
P O 
B y m o ut h , or al a d mi ni str ati o n of dr u g 
P R M C 
Pr ot o c ol R e vi e w a n d M o nit ori n g C o m mitt e e, M ar k e y C a n c er C e nt er  
Q A  
Q u alit y a s s ur a n c e  
Q D  
O n e a d a y; al s o “ q. d.” , “ q d”  
Q T c  
C orr e ct e d Q T i nt er v al, i n E K G s  
R N A  
Ri b o n u cl ei c A ci d  
R N A - S e q 
Ri b o n u cl ei c A ci d s e q u e n ci n g  
S A E 
S eri o u s a d v er s e e v e nt  
S A R S 
S e v er e a c ut e r e s pir at or y s y n dr o m e  
S A R S- C o V -2  S e v er e a c ut e r e s pir at or y s y n dr o m e c or o n a vir u s 2  
S O P 
St a n d ar d o p er ati n g pr o c e d ur e  
S R F  
S h ar e d r e s o ur c e f a cilit y  
TI D  
T hr e e ti m e s a d a y; al s o, “ t.i. d.” , “ti d” 
μ m ol/ L  
Mi cr o m ol e/lit er  
U K  
U ni v er sit y of K e nt u c k y  
U L N  
I n stit uti o n al u p p er li mit of n or m al 
W B C 
W hit e bl o o d c ell s  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
vii 
 
 
 
     


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
viii  
 
T A B L E O F C O N T E N T S  
 
1.  
O BJ E C TI V E S  ...................................................................................................................... 1 
1. 1  
Pri mar y O bjecti ve  .................................................................................................... 1 
1. 2  
Sec o n dar y O bjecti ves  ............................................................................................... 1 
1. 3  
E x pl orat or y O bjecti ves  ............................................................................................ 1 
2.  
B A C K G R O U N D  ................................................................................................................. 1 
2. 1  
S A R S -C o V - 2 Bac k gr o u n d ....................................................................................... 1 
2. 2  
I vermecti n  ................................................................................................................ 3 
2. 3  
Ca m ostat Mesilate  .................................................................................................... 3 
2. 4  
Arte misia a n n ua  ....................................................................................................... 4 
2. 5  
Artes u nate  ................................................................................................................ 5 
2. 6  
Rati o nale .................................................................................................................. 6 
2. 7  
C orrelati ve St u dies Bac k gr o u n d  .............................................................................. 7 
3.  
P A TI E N T S E L E C TI O N  ...................................................................................................... 8 
3. 1  
Eli gi bilit y Criteria  .................................................................................................... 8 
3. 2  
E xcl usi o n Criteria  .................................................................................................... 9 
3. 3  
I ncl usi o n of W o me n a n d Mi n orities ...................................................................... 1 1 
4.  
I N V E S TI G A T O R R E Q UI R E M E N T S A N D R E GI S T R A TI O N 
P R O C E D U R E S .................................................................................................................. 1 1 
4. 1  
I n vesti gat or a n d Researc h Ass ociate Re gistrati o n wit h M C C ............................... 1 1 
4. 2  
Cli nical Trial Re gistrati o n wit h cli nica ltrials. g o v a n d release of trial res ults ........ 1 1 
4. 3  
E nr oll me nt G ui deli nes  ........................................................................................... 1 1 
4. 4  
Dele gati o n of Tas ks L o g ( D T L) ............................................................................ 1 2  
4. 5  
I nf or me d C o nse nt................................................................................................... 1 2 
4. 6  
Recr uit me nt Pla ns:  ................................................................................................. 1 2 
4. 7  
Patie nt Scree ni n g O pti o ns  ...................................................................................... 1 3 
4. 8  
C o nse nt t o Treat me nt  ............................................................................................. 1 4 
4. 9  
Pati e nt Re gistrati o n t o Treat me nt  .......................................................................... 1 5 
4. 1 0  
Ge neral G ui deli nes ................................................................................................. 1 7  
5.  
BI O M A R K E R, C O R R E L A TI V E, A N D S P E CI A L S T U DI E S  ........................................ 1 7 
5. 1  
S u m mar y Ta ble f or S peci me n C ollecti o n  .............................................................. 1 7 
5. 2  
S peci me n Pr oc ure me nt Kits a n d Sc he d uli n g ......................................................... 1 8  
5. 3  
S peci me n C ollecti o n a n d Pr ocessi n g  ..................................................................... 1 8 
5. 4  
S hi p pi n g/ Dis pe nsi n g of S peci me ns ....................................................................... 2 0  
6.  
T R E A T M E N T P L A N  ........................................................................................................ 2 0 
6. 1  
A ge nt A d mi ni strati o n ............................................................................................. 2 0 
6. 2  
Defi niti o n of D ose- Li miti n g T o xicit y ( D L T) f or p hase I r u n i n p orti o ns of 
t his pr ot oc ol ........................................................................................................... 2 2 
6. 3  
D urati o n of T hera p y ............................................................................................... 2 2  
6. 4  
D ura ti o n of F oll o w-U p  .......................................................................................... 2 3 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
i x 
 
7.  
D O SI N G D E L A Y S/ D O S E M O DI FI C A TI O N S ................................................................ 2 3 
8.  
P H A R M A C E U TI C A L I N F O R M A TI O N  .......................................................................... 2 3 
8. 1  
Dr u g Or deri n g a n d Acc o u nta bilit y ........................................................................ 2 3  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S ............................................................................... 2 9 
9. 1  
St u d y Desi g n/ E n d p oi nts......................................................................................... 2 9  
9. 2  
Sec o n dar y E n d p oi nts ............................................................................................. 2 9  
9. 3  
Sa m ple  Size/ Accr ual Rate  ...................................................................................... 3 0 
9. 4  
Ra n d o mizati o n/ Stratificati o n Fact ors  .................................................................... 3 1 
9. 5  
Statistical A nal ysis Pla n  ......................................................................................... 3 2 
9. 6  
I nteri m A nal ysis ..................................................................................................... 3 2 
1 0.  
A D V E R S E E V E N T S:  LI S T A N D R E P O R TI N G R E Q UI R E M E N T S  ............................ 3 3 
1 0. 1  
E val uati o n of T o xicit y ........................................................................................... 3 3  
1 0. 2  
A d verse E ve nt C haracteristics  ............................................................................... 3 3 
1 0. 3  
M C C E x pe dite d A d verse E ve nt Re p orti n g G ui deli nes ......................................... 3 4  
1 0. 4  
E xce pti o ns t o A E re p orti n g .................................................................................... 3 6  
1 0. 5  
E x pe dite d Re p orti n g t o E xter nal A ge ncies ............................................................ 3 6  
1 0. 6  
E x pe dite d Re p orti n g t o t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) ...................... 3 6  
1 0. 7  
E x pe dite d Re p orti n g t o H os pital Ris k Ma na ge me nt ............................................. 3 6  
1 0. 8  
R o uti ne A d verse E ve nt Re p orti n g ......................................................................... 3 6  
1 0. 9  
Pre g na nc y ............................................................................................................... 3 7  
1 1.  
S T U D Y C A L E N D A R  ....................................................................................................... 3 8 
1 2.  
M E A S U R E M E N T O F E F F E C T ........................................................................................ 3 9 
1 2. 1  
E val uati o n of Res p o nse .......................................................................................... 3 9  
1 2. 2  
Ot her Res p o nse Para meters  ................................................................................... 3 9 
1 3.  
S T U D Y A P P R O V A L, O V E R SI G H T A N D D A T A R E P O R TI N G / 
R E G U L A T O R Y R E Q UI R E M E N T S ................................................................................. 3 9 
1 3. 1  
Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee a n d I nstit uti o nal Re vie w 
B oar d Re vie w ......................................................................................................... 3 9  
1 3. 2  
Q ualit y Ass ura nce .................................................................................................. 3 9  
1 3. 3  
Data a n d Safet y M o nit ori n g C o m mittee  ................................................................ 4 0 
1 3. 4  
Data Re p orti n g ....................................................................................................... 4 0  
1 3. 5  
Data Ma na ge me nt  .................................................................................................. 4 1 
1 3. 6  
C o m plia nce wit h La ws a n d Re g ulati o ns................................................................ 4 1  
1 4.  
R E F E R E N C E S  .................................................................................................................. 4 1 
A P P E N DI X A: O B E SI T Y S C A L E  ............................................................................................... 4 6 
A P P E N DI X  B: C O VI D 7 -P OI N T O R DI N A L O U T C O M E S S C A L E .......................................... 4 7 
A P P E N DI X C: PI L L/ Pr o d uct DI A RI E S  ....................................................................................... 4 8 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
x 
 
A P P E N DI X D: Tele healt h Tria ge a n d Dri ve/ T hr o u g h Wal k -i n E nr oll me nt ................................. 6 1 
A P P E N DI X E: Get Well L o o p/ Ce ntralize d C O VI D -1 9 Tele healt h at U K ( C T U) 
Al g orit h m  ........................................................................................................................... 6 2 
A P P E N DI X F: C urr e nt recr uit me nt strate g y a n d Sc he matic f or I nta ke a n d 
C o nse nt f or Researc h at Researc h Desi g nate d Cli nic  ........................................................ 6 3 
A P P E N DI X G: T o xicit y Gra di n g Scales f or Deter mi ni n g Se verit y of A d verse 
E ve nts ................................................................................................................................. 6 5  
A P P E N DI X H: O R D E RI N G I N S T R U C TI O N S F O R A R M E, A R T E MI LI F E 
T E A O R C O F F E E  ............................................................................................................. 7 8 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 
 
1.  O B J E C TI V E S  
 
1. 1  
Pri m ar y O bjecti ve  
 
T o ra pi dl y e val uate  i nitial efficac y of m ulti ple p ote ntial i n hi bit ors of S A R S -C o V -2 viral 
re plicati o n i n C O VI D 1 9 p ositi ve patie nts wit h hi g h-ris k fact ors i n or der t o decrease cli nical 
deteri orati o n, as defi ne d as a less t ha n a 2- p oi nt de crease fr o m i nitial C O VI D 7 -P OI N T 
O R DI N A L O U T C O M E S S C A L E w it hi n 1 4 da ys fr o m st u d y e ntr y.  
 
1. 2  
Sec o n d ar y O bjecti ves  
 
1. 2. 1  T o assess t he decrease  i n viral l oa d at Da y 1 4. 
1. 2. 2  T o assess t he de vel o p me nt of se vere  res pirat or y or ot her or ga n fail ure i n t he st u d y 
p o p ulati o n   
1. 2. 3  T o assess  pr o gressi o n t o I C U care or ve ntilati o n i n n o n-criticall y ill h os pitalize d patie nts  
a n d o verall st u d y p o p ulati o n 
1. 2. 4  T o assess cleara nce of viral R N A  b y P C R testi n g  at da ys 1, 1 4, 2 8, a n d 4 0 da ys 
1. 2. 5  T o assess m ortalit y, cli nical stat us of s u bject at Da y 1 4, usi n g t he C O VI D 7- p oi nt or di nal 
o utc o mes scale,  a n d rate of se vere a d verse e ve nts defi ne d as gra de 3 n o n he mat ol o gic or 
greater b y D MI D T o xicit y Scale f or Deter mi ni n g Se verit y of A d verse E ve nts  
1. 2. 6  T o assess t he safet y , t olera bilit y a n d c o m plia nce wit h  eac h re gi me n . 
 
1. 3  
E x pl or at or y O bjecti ves 
 
1. 3. 1  
T o o bser ve a n d  rec or d t he i m pact of eac h dr u g c o m bi nati o n o n i nfla m mat or y mar kers 
( pr ocalcit o ni n, D-Di mer , hs-C R P ) a n d t heir p ote ntial pr o g n ostic/ pre dicti ve val ue 
1. 3. 2  
T o deter mi ne t he rate a n d ti mefra me of S A R S -C o V -2 ser oc o n versi o n as a mar ker of 
ac q uire d i m m u nit y via t he p rese nce of C O VI D- 1 9 a nti b o dies i n R N A ne gati ve patie nts 
as a mar ker of ac q uire d i m m u nit y usi n g eit her a ra pi d dia g n ostic test ( R D T) or e nz y me-
li n ke d i m m u n os or be nt assa y ( E LI S A) assa y. 
1. 3. 3  
T o deter mi ne if earl y detecti o n of ele vate d i nfla m mat or y c yt o ki nes are p re dicti ve of 
se vere i nfecti o n or se vere disease .  
1. 3. 4  
T o perf or m p ost- h oc c o variate a dj uste d a nal ysis f or p ote ntial pre-treat me nt, o utc o me-
pr o g n ostic c o variates s uc h as a ge, se x, de gree of ill ness, cli nical c he mistries, a n d ti mi n g 
of o nset of s y m pt o ms relati ve t o st u d y i ncl usi o n. 
1. 3. 5  
T o e val uate t he effect of C O VI D - 1 9 o n platelet f u ncti o n t o assess se vere c oa g ulati o n 
c o m plicati o ns  
1. 3. 6  
T o e val uate viral cleara nce at Da y 1 4, 2 8 a n d 4 0 
 
2.  B A C K G R O U N D  
 
2. 1  
S A R S -C o V - 2 B ac k gr o u n d 
 
C or o na vir us Disease 2 0 1 9 ( C O VI D- 1 9) is a hi g hl y c o nta gi o us disease, ca use d b y a n o vel 
e n vel o pe d R N A beta-c or o na vir us, als o k n o w n as se vere ac ute res pirat or y s y n dr o me c or o na vir us-
2 ( S A R S -C o V - 2). [ 1] T he first case of t his u n prece de nte d o ut brea k “ p ne u m o nia of u n k n o w n 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 
 
eti ol o g y” was re p orte d i n W u ha n Cit y, H u bei Pr o vi nce, C hi na o n Dece m ber 8 t h, 2 0 1 9 a n d 
re p orte d t o t he W orl d Healt h Or ga nizati o n ( W H O) o n Dece m ber 3 1st, 2 0 1 9. [ 2] W H O declare d a 
C O VI D - 1 9 gl o bal e mer ge nc y o n Ja n uar y 3 0, 2 0 2 0, a n d t he n cate g orize d t he o ut brea k as a 
pa n de mic o n Marc h 1 1, 2 0 2 0. [ 3] As of A pril 2 2, 2 0 2 0, m ore t ha n 2, 6 2 8, 8 9 4 c o nfir me d cases of 
C O VI D - 1 9 w orl d wi de a n d 1 8 2, 7 4 0 pe o ple gl o ball y ha ve die d fr o m C O VI D-1 9 si nce it e mer ge d 
i n C hi na, acc or di n g t o t he data fr o m J o h ns H o p ki ns U ni versit y.  
 
W hile t he maj orit y of patie nts wit h C O VI D - 1 9 de vel o p mil d or u nc o m plicate d ill ness, 
a p pr o xi matel y 2 0- 3 0 % of h os pitalize d patie nts ha ve re q uire d i nte nsi ve care s u p p ort a n d 5 % of 
t h ose ha ve m ulti- or ga n fail ure or s h oc k. T he case fatalit y rate ra n ges fr o m 1 t o 4% a n d it is 
hi g her a m o n g t h ose wit h pre- e xisti n g c o m or bi d c o n diti o ns s uc h as car di o vasc ular disease, 
dia betes mellit us, o besit y, c hr o nic res pirat or y disease, h y perte nsi o n a n d ca ncer. [ 4] T he vast 
maj orit y of patie nts prese nts wit h fe ver ( 8 3 -9 9 % ), c o u g h ( 5 9- 8 2 %), fati g ue ( 4 4- 7 0 %), a n ore xia 
( 4 0-8 4 %), s h ort ness of breat h ( 3 1 - 4 0 %), s p ut u m pr o d ucti o n ( 2 8- 3 3 %), m yal gias ( 1 1- 3 5 %). [ 2, 5-
9] Less t ha n 1 0 % of patie nts will prese nt wit h hea dac he, c o nf usi o n, r hi n orr hea, s ore t hr oat, 
he m o pt ysis, v o miti n g, or diarr hea. [ 2, 5, 6] A n os mia or a ge usia pr ocee di n g t he o nset of 
res pirat or y s y m pt o ms has bee n a nec d otall y re p orte d. [ 1 0]   
 
T he Ce nter f or Disease C o ntr ol a n d Pre ve nti o n ( C D C) fr o m C hi na di vi de d t he cli nical 
ma nifestati o ns of t he disease as bel o w: [ 4] 
 
•  Mil d t o m o derate disease ( 8 1 %): n o n- p ne u m o nia a n d mil d p ne u m o nia  
•  S e vere disease ( 1 4 %): d ys p nea, res pirat or y fre q ue nc y ≥3 0/ mi n, bl o o d o x y ge n sat urati o n 
( S p O 2) ≤ 9 3 %, Pa O 2/ Fi O 2 rati o or P/ F [t he rati o bet wee n t he bl o o d press ure of t he 
o x y ge n ( partial press ure of o x y ge n, Pa O 2) a n d t he perce nta ge of o x y ge n s u p plie d 
(fracti o n of i ns pire d o x y ge n, Fi O 2)] < 3 0 0, a n d/ or l u n g i nfiltrates > 5 0 % wit hi n 2 4 t o 4 8 
h o urs 
•  Critical disease ( 5 %): res pirat or y fail ure, se ptic s h oc k, a n d/ or m ulti ple or ga n d ysf u ncti o n 
or fail ure  
 
T o c o n d uct p o p ulati o n -base d s ur veilla nce f or la b orat or y -c o nfir me d C O VI D - 1 9 –ass ociate d 
h os pitalizati o ns i n t he U S, t he C O VI D- 1 9 – Ass ociate d H os pitalizati o n S ur veilla nce Net w or k 
( C O VI D- N E T) was create d a n d re p orte d earl y data o n h os pitalizati o n rates fr o m Marc h 2 0 2 0.  
T he h os pitalizati o n rate a m o n g patie nts d uri n g t his 4- we e k peri o d was 4. 6 per 1 0 0, 0 0 0 
p o p ulati o n. Rates were hi g hest ( 1 3. 8) a m o n g a d ults a ge d ≥6 5 years. A m o n g a s u bset of t h ose 
a d ults 1 7 8 ( 1 2 %) wit h data o n u n derl yi n g c o n diti o ns, a n d c o nsiste nt wit h re p orts fr o m ot her 
c o u ntries, t he vast maj orit y ( 8 9. 3 %) ha d o ne or m ore u n derl yi n g c o n diti o ns: h y perte nsi o n 
( 4 9. 7 %), o besit y ( 4 8. 3 %), c hr o nic l u n g disease ( 3 4. 6 %), dia betes mellit us ( 2 8. 3 %), a n d 
car di o vasc ular disease ( 2 7. 8 %). T his earl y data fr o m C O VI D -N E T s u g gest t hat C O VI D - 1 9 –
ass ociate d h os pitalizati o ns i n t he U ni te d States ( U S) are hi g hest a m o n g ol der a d ults, a n d nearl y 
9 0 % of pers o ns h os pitalize d ha ve o ne or m ore of t hese u n derl yi n g me dical c o n diti o ns. [ 1 1] 
Gi ve n t hat t hese u n derl yi n g me dical c o n diti o ns are ra m pa nt i n t he state of Ke nt uc k y, a f oc us o n 
pre ve nti n g pr o gressi o n t o h os pitalizati o n a m o n gst t h ose w h o are m ost v ul nera ble t o C O VI D 1 9 
is warra nte d.  
 
A d diti o nall y, t o date, t reat me nts f or C O VI D- 1 9 i n hi g h ris ks i n di vi d uals re mai n e x peri me ntal 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 
 
a n d thera pe utic strate gies t o deal wit h t he i nfecti o n are at best s u p p orti ve, wit h pre ve nti o n ai me d 
at re d uci n g tra ns missi o n i n t he c o m m u nit y a s t he best wea p o n. N o pr o ve n t hera pies ha ve bee n 
de m o nstrate d t o pre ve nt pr o gressi o n of C O VI D- 1 9 t o se vere ill ness  a n d t his is a critical u n met 
nee d f or hi g h ris k i n di vi d uals a n d warra nts st u d y.  Rece ntl y, t he  I nfecti o us Disease S ociet y of 
A merica has ma de  rec o m me n dati o ns f or t he treat me nt of patie nts wit h C O VI D- 1 9, f oc usi n g o n 
i n patie nt care, a n d rec o m me n di n g ra n d o mize d trials w here p ossi ble as t he best ste p t o i m pr o ve 
treat me nt o utc o mes a n d t o i ncrease o ur u n dersta n di n g of t his c or o na vir us pa n de mic.  [ 1 2] 
Disc o veries i n t his area ma y i nf or m cli nicia ns o n effecti ve treat me nt f or  l o w ris k i n di vi d uals w h o 
pr o gress t o se vere ill ness , as well.   
 
2. 2  
Iver mecti n  
 
I ver mecti n is a n F D A a p pr o ve d a nti-parasitic a ge nt t hat als o has acti vit y a gai nst a n u m ber of  
R N A vir uses, i ncl u di n g i nfl ue nza, e q ui ne e nce p halitis a n d West Nile.  I ver mecti n i n hi bits t he 
i nteracti o n bet wee n t he h u ma n i m m u n o deficie nc y vir us-1 ( HI V - 1) i nte grase pr otei n (I N) a n d t he 
i m p orti n (I M P) α/ β 1 heter o di mer res p o nsi ble f or I N n uclear i m p ort. Its br o a d acti vit y a gai nst 
R N A vir uses is t h o u g ht t o be beca use of t he vir us’s relia nce o n I M Pα /Β 1 d uri n g i nfecti o n.  A 
rece nt p u blicati o n t hat e val uates the a nti viral acti vit y of i ver mecti n t o war ds S A R S - C o V- 2, i n 
vitr o a n d de m o nstrates a 9 9. 8 % re d ucti o n in cell -ass ociate d viral R N A  after 2 h o urs. [ 1 3] 
 
T he I C 5 0 f or i ver mecti n vers us Sars -C o V - 2 is 2. 5 u M = 2 1 8 0 u g/ L.[ 1 4] T he A U C of t he 
I ver mecti n i n h u ma ns at t he a p pr o ve d d ose i n ( 2 0 0 mc g/ k g) is 1 1 3 2 u g/ L.  T he c o nce ntrati o ns i n 
l u n g are a ntici pate d t o be 3 x hi g her t ha n plas ma e x p os ure.  [ 1 5] T heref ore we a ntici pate t hat we 
will ac hie ve a de q uate p ul m o nar y c o nce ntrati o ns t o ha ve a nti viral effect.  Gi ve n its safet y pr ofile, 
we will use t he F D A a p pr o ve d d ose of i ver mecti n i n t his trial, as we are c o m bi ni n g it wit h H C Q.  
 
2. 3  
C a m ost at Mesil ate  
 
Rece ntl y, mec ha nistic st u dies ha ve el uci date d t hat a critical ste p f or S A R S -C o V - 2 viral e ntr y is 
t he pri mi n g of t he S A R S- C o V 2 s pi ke pr otei n, w hic h uses t he h u ma n seri ne pr otease T M P R S S 2. 
N ota bl y, c a m ostat mesilate  ( C A M), a p ote nt i n hi bit or of seri ne pr oteases, has bee n s h o w n t o 
bl oc k cell ular viral e ntr y of S A R S- C o V -2 i n pri mar y h u ma n air wa y e pit helial cells. [ 1 6]Ca m ostat 
bl oc k S A R S- C o V - 2 re plicati o n i n T M P R S S 2-e x pressi n g h u ma n cells, wit h a n a p pare nt E C 9 0 of 
3 µ M, a n d si g nifica ntl y lesse ns viral re pli cati o n at t hat le vel.[ 1 7]  Ca m ostat has bee n s h o w n t o 
bl oc k i nfecti o n wit h S A R S- C o V - 1 i n h u ma n cells wit h r o u g hl y e q ui vale nt p ote nc y.[ 1 8]  I n a 
m o use m o del of S A R S- C o V- 1 a d ose of t wice dail y at 3 0 m g/ k g, e q ui vale nt t o a 2 7 5 m g d ose i n 
a 7 0 k g h u ma n, pr o vi di n g a s ur vi val a d va nta ge.[ 1 9]   A d diti o nall y, ca m ostat  has bee n s h o w n t o 
atte n uate air wa y e pit helial s o di u m c ha n nel f u ncti o n a n d e n ha nce m uc ociliar y cleara nce w he n 
ne b ulize d i nt o t he trac hea of c o nsci o us s hee p.  [ 2 0] T his a nal ysis was e xte n de d t o c ystic fi br osis 
patie nts i n a s mall trial w here is was a d mi nistere d via a nasal s pra y p u m p a n d was s h o w n t o 
re d uce s o di u m tra ns p ort i n t he air wa y a n d was well t olerate d, s u g gesti n g t he p ossi bilit y t hat t his 
mi g ht i ncrease cle ara nce of i nfecti o us viri o ns. [ 2 1] Ca m ostat  is a p pr o ve d f or re missi o n of ac ute 
s y m pt o ms of c hr o nic pa ncreatitis a n d p ost - o perati ve es o p ha geal refl u x. A d diti o nall y , ca m ostat 
was a p pr o ve d i n t he U nite d States u n der I N D 1 0 9 0 3 5 f or t he relief of a b d o mi nal pai n ass ociate d 
wit h c hr o nic pa ncreatitis  a n d b y t he F D A f or  use a gai nst S A R S -C o V - 2 i n t his cli nical trial (I N D 
1 5 1 0 3). At t his ti me, t he cli nical i m pact of ca m ostat  o n C O VI D - 1 9 is n ot k n o w n, t h us, we pla n 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 
 
t o e xa mi ne w het her ca m ostat  ca n i m pr o ve patie nt o utc o mes. 
 
Ca m ostat is a p pr o ve d f or c hr o nic pa ncreatitis i n Ja pa n at a dail y d ose of 6 0 0 m g.  We are usi n g 
t he sa me d ose i n t his cli nical trial.  I n a m uri ne e x peri me nt, f oll o wi n g a let hal S A R S- C o V 
i nfecti o n, t he s ur vi val rate of ca m ostat treate d mice was 6 0 %.[ 1 9]  I n t his st u d y, mice were 
treate d at 3 0 m g/ k g f or 9 da ys.  A c orres p o n di n g d ose i n a 7 5 k g h u ma n w o ul d be 2 2 5 0 m g.  
Ca m ostat mes ilate was well t olerate d b y patie nts w he n a d mi nistere d t hree ti mes per da y at a d ose 
of 2 0 0 m g (t otal dail y d ose of 6 0 0 m g), a n d t his is t he a p pr o ve d d ose a n d sc he d ule i n Ja pa n f or 
c hr o nic pa ncreatitis. [ 2 2] Gi ve n t hat we are treati n g o ut patie nts, f or a 1 4- da y d urati o n, we 
a ntici pate  usi n g t he a p pr o ve d d ose i n Ja pa n is a reas o na ble starti n g p oi nt a n d we will c o nsi der a 
d ose escalati o n if t olera ble a n d t here are hi nts of efficac y.  
 
2. 4  
Arte misi a a n n u a  
 
Arte mis ia a n n ua, als o k n o w n as s weet w or m w o o d, is a b ota nical pr o d uct nati ve t o Asia b ut 
gr o ws i n ma n y c o u ntries, i ncl u di n g t he U nite d States. Arte misia  a n n ua has bee n use d f or 
ce nt uries as i nf usi o ns or p o w ders t o treat malaria. Arte misi ni n is e xtracte d fr o m Arte misia  
a n n ua, a n d artes u nate is t he n se mi -s y nt heticall y deri ve d fr o m arte misi ni n.[ 3 8]. Artes u nate is a 
hi g hl y effecti ve treat me nt f or malaria b ut is li mite d b y t he ra pi d de vel o p me nt of resista nce a n d 
m ust be use d i n c o m bi nati o n wit h ot her a nti malarials .[ 3 9]  I ntri g ui n gl y, Arte misia  a nn u a tea, 
w hic h c o ntai ns a mi xt ure of acti ve c o nstit ue nts, i ncl u di n g di h y dr oarte misi nic aci d, arte misi nic 
aci d, a n d arte misi ni n, ma y be m ore effecti ve t ha n artes u nate i n treati n g malaria. A ra n d o mize d, 
place b o -c o ntr olle d cli nical trial e nr olli n g 9 5 7 patie nt s wit h malaria c o m pare d Arte misia  a n n ua 
tea t o artes u nate-a m o dia q ui ne t hera p y. Patie nts were ra n d o mize d t o recei ve eit her artes u nate -
a m o dia q ui ne ta blets or Arte misia  a n n ua tea wit h 1. 6 g of t wi gs a n d lea ves / 0. 3 3 L e ver y 8 h o urs 
f or 7 da ys. Tea was pre pare d b y a d di n g 5 g of Arte misia  a n n ua drie d lea ves a n d t wi gs t o 1 liter 
of b oili n g water. T he pri mar y e n d p oi nt of t his trial was t he malaria c ure rate, wit h t he Arte misia  
a n n ua c ure rate of 9 6. 4 % at 2 8 da ys c o m pare d t o o nl y 3 4. 3 % i n t he artes u nate-a m o dia q ui ne ar m. 
[ 4 0]  Arte misia  a n n ua tea was als o well-t olerate d, wit h 5 % of s u bjects e x perie nci ng na usea or 
v o miti n g, alt h o u g h n o ne se vere e n o u g h t o disc o nti n ue t hera p y a n d n o ot her a d verse effects 
re p orte d. I n c o ntrast, 4 2. 8 % of patie nts i n t he artes u nate-a m o dia q ui ne ar m re p orte d a d verse 
effects, i ncl u di n g na usea, ast he nia, pr urit us, h y p o gl yce mia, a n d verti g o.   
 
T he a nti viral acti vit y of Arte misia  a n n ua a n d p ure Arte misi ni n a n n ua was teste d b y pretreati n g 
Ver o E 6 l u n g cells i nfecte d wit h S A R S- C o V - 2 o ver 1 2 0 mi n utes at a c o nce ntrati o n of 1 3 0 
pla q ue f or mi n g u nites per well. A q ue o us a n d et ha n olic e xtracts of Arte misi ni n a n n ua , a n d 
arte misi ni n c o nce ntrati o ns ra n gi n g fr o m 0- 2. 5 u g/ m L were i nc u bate d wit h vir us i nfecte d cells f o r 
1 5, 3 0, 6 0 a n d 1 2 0 mi n utes.  B ot h t he a q ue o us a n d et ha n olic e xtracts s h o we d s u bsta ntial acti vit y, 
a n d were a ble t o i n hi bit a p pr o xi matel y 5 0 % of viral re plicati o n at c o nce ntrati o ns of 1. 5 u g/ m L.  
B y c o m paris o n, p ure Arte misi ni n was n ot a ble t o i n hi bit t he vir us b y 5 0 % a n d n o E C 5 0 was a ble 
t o be calc ulate d.  T heref ore, t he e xtracts were a d va nce d f or f urt her cli nical testi n g.[ 4 1]  
T he d ose f or t his st u d y is base d o n e x perie nce wit h malaria, w here c hil dre n as y o u n g as 5 years 
of a ge recei ve d a d ose of tea ( 1. 6 g/ 0. 3 3 L) e ver y 8 h o urs f or 7 da ys wit h t he o nl y re p orte d 
a d verse effect t o be mil d na usea a n d v o miti n g.  N ota bl y, 1. 6 g of t wi gs a n d lea ves as use d i n t he 
malaria st u d y c orres p o n ds t o 2 2 1 m g of leaf al o ne.[ 4 2] W hile t here is a pa ucit y of e x perie nce 
wit h h u ma n p har mac o ki netic st u dies i n patie nts recei vi n g Arte misia  a n n ua tea,[ 4 0] i n rats, 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 
 
recei vi n g t he sa me d ose, t he c o nce ntrati o n of t he acti ve c o nstit ue nt, Arte misi ni n was 1 0 u g/ m L 
i n ser u m, a n d 5 u g/ m L i n t he l u n g after a si n gle d ose[ 4 3]   T he Arte misia  a n n ua decaf c offee 
p o ds a n d tea ba gs use d i n t his st u d y are c o m merciall y a vaila ble b ota nical pr o d ucts a n d s u p plie d 
b y Arte mi Life I nc. ( htt ps://arte milife.c o m/ h o me). Arte misia  a n n ua decaf c offee p o ds c o ntai n 4 5 0 
m g Arte misia  a n n ua leaf, a n d tea ba gs c o ntai n 2 2 5 m g Arte misia  a n n ua leaf.  T heref ore, we 
a ntici pate a de q uate c o nce ntrati o ns t o ac hie ve a nti viral acti vit y w hile mai ntai ni n g e xcelle nt 
t olera bilit y.  T he decaf c offee p o ds a n d tea ba gs c o ntai n F D A f o o d- gra de q ualit y i n gre die nts. 
Arte misia  a n n ua pla nts f or Ar te mi Life c offee a n d tea are gr o w n i n Ke nt uc k y. Arte mi Life c offee 
p o ds a n d tea ba gs are pr o d uce d a n d ma n ufact ure d i n t he U nite d States. 
 
2. 5  
Artes u n ate  
 
Arte misi ni n is e xtracte d fr o m Aa a n d artes u nate is t he n se mi -s y nt heticall y deri ve d fr o m 
arte misi ni n.[ 3 9] [ 4] .  Artes u nate is a hi g hl y effecti ve treat me nt f or malaria, b ut w hile hi g hl y 
effecti ve, artes u nate is li mite d b y t he ra pi d de vel o p me nt of resista nce a n d m ust be use d i n 
c o m bi nati o n wit h ot her a nti malarials.[ 4 0] [ 5]. T he us ual d ose of artes u nate i n a d ults f o r malaria 
is 2 0 0 m g o nce a da y f or 7 da ys a n d has bee n use d i n ca ncer st u dies at a d ose of 2 0 0 m g a da y 
f or u p t o 3 7 m o nt hs.[ 4 2]  T heref ore, i n t his st u d y we will a d mi nister 2 0 0 m g orall y dail y f or a 
t otal of 1 4 da ys.   
 
I n  a  ra n d o mize d  efficac y  a n d  safet y  trial  c o m pari n g  t w o  artes u nate  c o m bi nati o n  t hera pies, 
artes u nate  +  a m o dia q ui ne  ( A S A Q)  a n d  arte met her  +  l u mefa ntri ne  ( A L),  i n  c hil dre n  wit h  
u nc o m plicate d malaria, 2 2 7 s u bjects wit h a n a ge ra n ge of 6 m o nt hs t o 1 4 years were f oll o we d f or 
2 8 da ys after treat me nt, t he n m o nt hl y f or a year. [ 4 4] T he A S A Q gr o u p was treate d o nce dail y wit h 
1 0 m g / k g b o d y A Q a n d 4 m g/ k g A S f or 3 da ys. T he A L gr o u p was a d mi nistere d a si n gle d ose of 
2 0 m g arte met her a n d 1 2 0 m g l u mefa ntri ne o n t he first da y, t he n t w o d oses o n da y 2 a n d 3, wit h 
d osi n g at o ne ta blet/ d ose f or b o d y wei g ht of 5 -1 4 k g, t w o ta blets/ d ose f or b o d y wei g ht of 1 5 - 2 4 
k g, t hree ta blets/ d ose f or b o d y wei g ht of 2 5 -3 4 k g, or f o ur ta blets/ d ose wit h a b o d y wei g ht 3 5 k g 
or greater. B ot h A S A Q a n d A L were hi g hl y effecti ve wit h a de q uate cli nical a n d parasit ol o gical 
res p o nse rates of 9 7. 1 % a n d 9 8. 2 % at da y 1 4 f or t he A L a n d A S A Q gr o u ps, res pecti vel y. B ot h 
artes u nate c o m bi nati o n t hera pies were well t olerate d, wit h mil d na usea a n d v o miti n g t he m ost 
c o m m o n a d verse effects , wit h 2 7. 5 % a n d 1 2. 6 % of s u bjects re p orti n g eac h, res pecti vel y.[ 4 4]  
 
P har mac o ki netics of artes u nate was c o m plete d i n a m ultice nter trial wit h 4 7 2 Africa n pe diatric 
s u bjects wit h u nc o m plicate d malaria. One or t w o fi xe d -d ose ta blets of artes u nate - mefl o q ui ne ( 2 5 
m g/ 5 5 m g) were c o ns u me d dail y f or t hree da ys. D osi n g was base d o n a ge. S u bjects bet wee n 6 t o 
1 1  m o nt hs  were  a d mi nistere d  o ne  ta blet  dail y,  a n d  s u bjects  bet wee n  1 2  t o  5 9  m o nt hs  were 
a d mi nistere d t w o ta blets dail y. Bl o o d dra ws were c o m plete d o n 5 0 s u bjects f or P K a nal ysis. Bl o o d 
dra ws were perf or me d at re g ular i nter vals, i ncl u di n g pre d ose t o 6 hrs after first d ose, pre d ose t o 6 
hrs after t hir d d ose, 7 2 hrs after first d ose, o n da y 7, a n d o n o ne da y bet wee n da y 2 8 a n d da y 6 3. 
F or artes u nate t he A U C 0- 2 4, d a y 0 was 0. 3 4  n g/ L/ h, a n d t he  A U C 0- 2 4, da y 2 was 0. 2 3 n g/ L/ h. T he C ma x 
was 0. 5 2 n m ol/ m L, a n d t he ter mi nal half -life was 4 0 mi n. F or D H A, t he A U C 0- 2 4, da y 0 was 3. 3 0  
n g/ L/ h, a n d t he  A U C 0- 2 4, da y 2 was 2. 2 0 n g/ L/ h. T he C ma x was  3. 9 n m ol/ m L f or D H A, a n d t he 
ter mi nal half-life was 4 0 mi n [ 4 5]. 
 
Artes u nate has bee n re p orte d t o be well t olerate d i n c hil dre n wit h malaria. A ra n d o mize d efficac y 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 
 
a n d safet y trial c o m pari n g  artes u nate + a m o dia q ui ne  a n d arte met her + l u mefa ntri ne ( A L) was 
c o n d ucte d i n 2 2 7 s u bjects wit h malaria wit h a n a ge ra n ge of 6 m o nt hs t o 1 4 years. A d verse e ve nts 
were re p orte d t o be si milar bet wee n t he treat me nt gr o u ps. B ot h artes u nate c o m bi nati o n t hera pies 
were well t olerate d, wit h mil d na usea a n d v o miti n g t he m ost c o m m o n a d verse effects, wit h 2 7. 5 % 
a n d 1 2. 6 % of s u bjects re p orti n g eac h, res pecti vel y . H o we ver, a hi g her perce nta ge of s u bjects 
re p orte d na usea ( 4 0. 5 %) a n d v o miti n g ( 4 4. 8 %) bef ore be gi n ni n g treat me nt. 4. 3 % of s u bjects i n 
A S A Q gr o u p a n d 3. 6 % of s u bjects i n t he A L gr o u p  re p orte d fati g ue a n d e xcessi ve slee pi ness. 
Pr urit us was re p orte d f or 3 patie nts i n t he st u d y. 1 2 % of s u bjects i n t he A S A Q gr o u p a n d 8 % i n 
t he  A L  gr o u p  re p orte d  dizzi ness  a n d  se vere  a ne mia  was  re p orte d  i n  o ne  s u bject;  h o we ver,  
i n vesti gat ors deter mi ne d t hat b ot h s y m pt o ms were li kel y u nrelate d t o treat me nt. [ 4 4]  
 
A n ot her m ultice nter, ra n d o mize d st u d y c o m pare d fi xe d d ose artes u nate + a m o dia q ui ne o nce dail y 
( A S A Q 1) or t wice dail y (A S A Q 2 ) wit h arte met her + l u mefa ntri ne  ( A L) i n 9 4 1 patie nts wit h 
u nc o m plicate d malaria. T he mea n a ge f or t he A S A Q 1 gr o u p was 9. 5 years ( S D - 1 0. 8), f or t he 
A S A Q 2 gr o u p was 9. 1 years ( S D - 9. 8), a n d f or t he A L gr o u p was 9. 4 years ( S D - 1 0. 7). 2 9. 3 % of 
patie nts ha d at least o ne a d verse e ve nt, 2 0. 4 % were t h o u g ht t o be relate d t o treat me nt. M ost a d verse 
e ve nts ( 8 8. 5 %) were  c o nsi dere d  mil d  or  m o derate,  wit h  2 4. 4 %  e x perie nci n g  i ns o m nia  or  
s o m n ole nce a n d 1 6. 7 % gastr oi ntesti nal s y m pt o ms, wit h 1 3 % of s u bjects re p orte d t o ha ve v o miti n g 
wit hi n 3 0 mi n utes of treat me nt. 7 patie nts were re p o rte d t o ha ve a ne mia, wit h o ne patie nt re q uiri n g 
h os pitalizati o n b ut ulti matel y rec o vere d. T w o s u bjects die d d uri n g t he st u d y, b ut t he deat hs were 
n ot attri b ute d t o t he treat me nt. [ 4 6]  
 
2. 6  
R ati o n ale 
 
We pr o p ose t he use of a m ulti- ar m, p hase II “ pic k -t he-wi n ner” trial desi g n t o  all o w i nitial 
assess me nt of m ulti ple t hera pies i n parallel a n d selecti o n of pr o misi n g t hera pies wit h a de q uate 
pr o ba bilities after C O VI D 1 9 + testi n g  i n hi g h ris k, b ut n o n-criticall y ill i n di vi d uals. [ 4 7] Pri or t o 
m o vi n g a pr o misi n g t hera pe utic a ge nt f or war d i nt o lar ge ra n d o mize d trials of t his t hera p y vers us 
place b o, i n vesti gat ors nee d t o pr o vi de s u bsta ntial e vi de nce of effecti ve ness a n d a de q uate 
c haracterizati o n of safet y.  I n a d diti o n, we i nc or p orate ra pi d f utilit y a nal ysis w here eac h a ge nt is 
assesse d i n de pe n de ntl y usi n g Ba yesia n p osteri or  pr o ba bilit y calc ulati o ns. N O T E: t his is b ase d 
o n effic ac y n ot t o xicit y assess me nt.  T he t o xicit y assess me nt will be d o ne usi n g r u n -i ns f or 
s o me of t he ar ms.  T his selecti o n desi g n a p pr oac h al o n g wit h i nteri m assess me nts of efficac y,, 
use d ofte n i n ot her disci pli nes s uc h as o nc ol o g y, all o ws f or i nitial assess me nt of p ote ntial be nefit 
usi n g statistical pr o ba bilit y calc ulati o ns, bef ore desi g ni n g ra n d o mize d c o m parati ve trials t o a v oi d 
e x p osi n g lar ge n u m bers of s u bjects t o p ote ntiall y f ut ile a ge nts. T he “ pic k t he wi n ner” trial desi g n 
a n d Ba yesia n p osteri or pr o ba bilit y met h o ds all o w f or a n a da pti ve, pr o of- of- c o nce pt strate g y 
w hic h i nc or p orates pr os pecti vel y pla n ne d criteria t o st o p eac h ar m i n de pe n de ntl y f or f utilit y, [ 4 8] 
[ 4 9] wit h t he pr os pect of e x pa n di n g fr o m a pr o of- of-c o nce pt p hase t o a lar ger c o nfir mat or y trial , 
t y picall y a ra n d o mize d, place b o c o ntr olle d trial, if i nitial assess me nts are p ositi ve.  T he 
h y p ot hesis of t his st u d y is t hat t he a d diti o n of a ge nts t hat i n hi bit viral e ntr y or re plicati o n of 
S A R S -C o V - 2 vir us, will be de v oi d of a d diti o nal m o derate t o se vere t o xicit ies, will pre ve nt 
cli nical deteri orati o n  at 1 4 da ys , a n d will  i m pr o ve viral cleara nce at Da y 14 i n hi g h ris k 
i n di vi d uals. A d diti o nall y, we h y p ot hesize t hat cli nical o utc o mes i n C O VI D - 1 9 i nfecte d patie nts 
at hi g her ris k of p o or o utc o mes f oll o wi n g i nfecti o n will be i m pr o ve d c o m pare d t o t he e mer gi n g 
sta n dar ds w he n i ntr o d uce d as a n earl y i nter ve nti o n after dia g n osis .  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
7 
 
 
 
C O VI D 7 - p oi nt Or di nal O utc o me Scale a n d Pri mar y E n d p oi nt 
2. 7  
C orrel ati ve St u dies B ac k gr o u n d  
 
2. 7. 1  S A R S -C o V - 2 Vir al L o a d  
Acti ve S A R S -C o V - 2 i nfecti o n is dia g n ose d b y q P C R i n u p per a n d l o wer res pirat or y s peci me ns 
o btai ne d b y nas o p har y n geal s wa bs.  T he i nitial, dia g n ostic test is perf or me d at baseli ne i n a 
C LI A la b orat or y a n d re q uire d f or dia g n ostic p ur p oses a n d f or st u d y e ntr y .  S u bse q ue nt sa m ples, 
t o a v oi d placi n g b ur de n o n cli nical res o urces, will be researc h le vel or o p har y n geal s wa bs or 
s p ut u m sa m ples a n d e val uate d i n t he K olesar la b orat or y b y a vali date d q P C R assa y.  I n a d diti o n, 
a n y resi d ual s peci me n fr o m nas o p har y n geal s wa bs t hat are c ollecte d f or r o uti ne care d ue t o a 
cli nical i n dicati o n t o retest usi n g a C LI A la b orat or y assa y  will be c ollecte d .  C orrelati ve testi n g 
will e xa mi ne t he li n ka ge of viral l oa d wit h ti me t o res ol uti o n a n d wit h cli nical stat us, as well as 
c orrelati o n bet wee n viral l oa d a n d ser o p ositi vit y, recr u desce nce, of disease a n d cli nical 
o utc o mes. 
 
2. 7. 2  S A R S -C o V - 2 A nti b o d y S er o p ositi vit y 
Defi niti ve met h o ds t o pr o ve a patie nt ha d bee n i nfecte d wit h S A R S- C o V -2 are c urre ntl y lac ki n g.  
Se veral gr o u ps wit hi n t he U K s y ste m are de vel o pi n g ser ol o g y tests t o detect S A R S-C o V - 2 
a nti b o dies.  Dr. Sc ott Berr y, a n Ass ociate Pr ofess or i n E n gi neeri n g at t he U ni versit y of Ke nt uc k y 
a n d C hief Scie ntific Officer of Salas Disc o ver y, is a n e x pert t he de vel o p me nt of p oi nt of care 
testi n g f or viral dia g n ostics.  He has a da pte d a n e mer gi n g tec h n ol o g y i n bi o mar ker 
is olati o n/ meas ure me nt, E xcl usi o n-base d Sa m ple Pre parati o n ( E S P), f or t he u n met cli nical nee d 
ass ociate d wit h p oi nt of care S A R S -C o V -2 meas ure me nt. [ 5 0] T his ser ol o g y test c o m bi nes t he 
se nsiti vit y a n d q ua ntitati ve nat ure of a n E LI S A wit h t he s pee d a n d si m plicit y of a lateral fl o w 
assa y (i.e., a ra pi d test) [ 5 1- 5 3]  Briefl y, E S P utilizes p hase i nterfaces (e. g., li q ui d/air b o u n daries) 
t o ra pi dl y a n d si m pl y ma ni p ulate a nal yte b o u n d t o para ma g netic particles ( P M Ps) wit hi n a b ul k 
sa m ple. E S P will be use d t o is olate S A R S -C o V -2 a nti b o d y fr o m a bl o o d sa m ple a n d t he n 
perf or m a strea mli ne d, E S P - base d i m m u n oassa y f or q ua ntitati o n S A R S - C o V- 2a nti b od y . 
I m p orta ntl y, E S P t hat has bee n s uccessf ull y i m ple me nte d as t he bac k b o ne of a ne w HI V assa y 
geare d t o war d de vel o pi n g c o u ntries, ill ustrati n g its a bilit y t o f u ncti o n o utsi de of s o p histicate d 
la bs.[ 5 4, 5 5]   
 
Me m bers of t he U ni versit y of Ke nt uc k y C U R E A llia nce i ncl u di n g Dr. Jerr y W o o d war d has 
e x pertise i n de vel o p me nt of i m m u ne pr ofili n g a n d i n c olla b orati o n wit h ot her me m bers of t he 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
8 
 
De part me nt of Micr o bi ol o g y, I m m u n ol o g y, a n d M olec ular Ge netics a n d ot her c olla b orat ors is 
de vel o pi n g a n i n -h o use ser ol o gical assa y t o test f or t he prese nce of a nti b o dies t o S A R S -C o V - 2 
i nfecti o n i n bl o o d a n d sali va w hic h will be critical t o o ur a bilit y t o u n dersta n d i m m u nit y t o t his 
vir us f oll o wi n g i nfecti o n. A d diti o nall y, his gr o u p will p urs ue c o m plete i m m u ne pr ofili n g of 
plas ma base d m o n o n uclear cells ( P B M Cs) w hic h is a n ass ociate d a n d critical part of e x pa n di n g 
o ur u n dersta n di n g of t he a da pti ve i m m u ne res p o nse t o t his n o vel vir us. 
 
2. 7. 3  I nfl a m m at or y C yt o ki nes 
Pri or st u dies ha ve de m o nstrate d t hat pr oi nfla m mat or y c yt o ki nes are ass ociate d wit h p ul m o nar y 
i nfiltrates a n d se vere i nfecti o n i n i n di vi d uals wit h S A R S, [ 5 6] M E R S - C o V  [ 5 7] a n d S A R S-
C o V - 2 [ 2] i nfecti o n.  We h y p ot hesize t hat i nfla m mat or y c yt o ki nes li ke T N F al p ha, I L- 1, I L- 2 
a n d I L- 6 will be ele vate d at baseli ne a n d da y 7 i n i n di vi d uals w h o g o o n t o de vel o p a se vere 
i nfecti o n w he n c o m pare d t o t h ose w h o d o n ot de vel o p a se vere i nfecti o n a n d t hat c yt o ki ne 
meas ure me nt ca n be a n earl y mar ker of se vere i nfecti o n, all o wi n g f or earlier i n ter ve nti o n i n 
t hese i n di vi d uals.  C yt o ki ne le vels will be meas ures b y t he E LI S A i n t he K olesar la b, b y Dr. Jill 
K olesar, as pre vi o usl y descri be d. [ 5 8]     
 
2. 7. 4  C o a g ul o p at h y i n C O VI D- 1 9 P atie nts 
Dr. Si d ne y W hite heart ( M olec ular a n d Cell ular Bi oc he mistr y) a n d Dr. Jere m y W o o d ( Me dici ne) 
ha ve de vel o pe d a c olla b orati o n t o st u d y t he c oa g ul o pat hies ass ociate d wit h C O VI D - 1 9 
patie nts.   S pecificall y, t heir f oc us is o n t he d ysf u ncti o n of n or mal he m ostatic c o ntr ol see n i n t he 
m ost se vere C O VI D -1 9 patie nts.   Re p orts fr o m C hi na, Ital y, a n d t he U S ha ve s h o w n a n i ncrease 
i n c oa g ul o pat hies i n C OVI D -1 9: prese nti n g as i ncrease d D -di mer, t hr o m b oc yt o pe nia, a n d 
t hr o m b otic micr oa n gi o pat h y.  T his cli nical ma nifestati o n has lea d I S T H a n d A S H t o rec o m me n d 
l o w m olec ular wei g ht he pari n i n cases w here C O VI D- 1 9 is se vere; h o we ver, t he u n derl yi n g 
ca uses of t his are u n k n o w n.  Drs. W hite heart a n d W o o d will use t heir s pecific e x pertise a n d 
batter y of f u ncti o nal assa ys t o st u d y t his c oa g ulati o n d ysf u ncti o n at b ot h t he c oa g ulati o n fact or 
a n d platelet le vel.   W h ole bl o o d is nee de d f or s o me of t he platelet-s pecific assa ys a n d plas ma 
will be retai ne d f or a nal ysis.   T he data ge nerate d will hel p deter mi ne w hat ca uses t he i ncrease d 
c oa g ulati o n a n d will g ui de h o w t o better ma na ge a ntic oa g ula nt t hera p y i n t he m ost se verel y 
affecte d patie nts.  
 
 
3.  P A TI E N T S E L E C TI O N  
 
3. 1  
Eli gi bilit y Criteri a  
 
3. 1. 1  A ge ≥1 8 years  
 
3. 1. 2  La b orat or y -c o nfir me d S A R S-C o V - 2 i nfecti o n wit hi n 7 da ys ( of pr o p ose d c o nse nt) or t he 
prese nce of  s y m pt o ms or p h ysical e xa mi nati o n si g ns pr o vi di n g hi g h pr o ba bilit y of 
C O VI D -1 9 disease des pite a ne gati ve C O VI D -1 9 test as deter mi ne d  b y I nfecti o us 
Disease s pecialist/ C O VI D -1 9 Tele healt h Treat me nt Tea m re vie w  
 
3. 1. 3  S u bjects m ust ha ve at least o ne of t he f oll o wi n g hi g h- ris k feat ures f or cli nical 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
9 
 
deteri orati o n:  
- 
H y perte nsi o n 
- 
Dia betes Mellit us  
- 
M o derate t o se vere C hr o nic O bstr ucti ve P ul m o nar y Disease , E m p h yse ma, C ystic 
Fi br osis,  or Ast h ma  
- 
Ca ncer  patie nts w h o ha ve recei ve d a n y i m m u n os u p pressi ve dr u gs wit hi n a year fr o m 
e nr oll me nt.  
- 
Sic kle cell disease  or  t halasse mia  
- 
A ge > 5 0 
- 
B MI > 3 0  
- 
Li vi n g i n a n ursi n g h o me or l o n g- ter m facilit y 
- 
U n derl yi n g seri o us heart c o n diti o n as deter mi ne d b y t he treati n g p h ysicia n 
- 
I m m u n oc o m pr o mise d s u bject as defi ne d b y t he treati n g p h ysicia n  or C O VI D - 1 9 
Tele healt h Treat me nt Tea m   
 
3. 1. 4  A bilit y t o pr o vi de i nf or me d c o nse nt b y t he patie nt or healt hcare pr o x y 
 
3. 1. 5  A bilit y t o ret ur n f or re peate d testi n g a n d o bser vati o n t o U K H C 
 
3. 1. 6  Patie nts m ust ha ve a de q uate or ga n a n d marr o w f u ncti o n meas ure d wit hi n t he last 3 0 da ys 
as defi ne d bel o w:  
 
− 
platelets    
 
≥1 0 0, 0 0 0/ mc L 
− 
A S T( S G O T)/ A L T( S G P T)    
≤3 × i nstit uti o nal U L N  
− 
creati ni ne   
 
≤ 1. 5 x i nstit uti o nal U L N 
O R  
− 
gl o mer ular filtrati o n rate ( G F R)  ≥4 5 m L/ mi n/ 1. 7 3 m 2 u nless data e xists s u p p orti n g 
safe use at l o wer ki d ne y f u ncti o n val ues, n o l o wer 
t ha n 3 0 m L/ mi n/ 1. 7 3 m2 (see A p pe n di x B).   
 
3. 1. 7  T he effects of t hera pe utic a ge nts use d i n t his trial o n t he de vel o pi n g h u ma n fet us are 
u n k n o w n.  Beca use t hera pe utic a ge nts use d i n t his trial ma y  be terat o ge nic, w o me n of 
c hil d- beari n g p ote ntial a n d me n m ust a gree t o use a de q uate c o ntrace pti o n ( h or m o nal or 
barrier met h o d of birt h c o ntr ol; a bsti ne nce) pri or t o st u d y e ntr y a n d f or t he d urati o n of 
st u d y partici pati o n.  S h o ul d a w o ma n bec o me pre g na nt or s us pect s he is pre g na nt w hile 
s he or her part ner is partici pati n g i n t his st u d y, s he s h o ul d i nf or m her treati n g p h ysicia n 
i m me diatel y.  Me n treate d or e nr olle d o n t his pr ot oc ol m ust als o a gree t o use a de q uate 
c o ntrace pti o n pri or t o t he st u d y, f or t he d urati o n of st u d y partici pati o n. 
 
3. 2  
E xcl usi o n Criteri a  
 
3. 2. 1  Se vere C O VI D - 1 9 is defi ne d b y o ne or m ore of t he f oll o wi n g: 
- 
bl o o d o x y ge n sat urati o n ≤ 9 0 %  
- 
partial press ure  of arterial o x y ge n t o fracti o n of i ns pire d o x y ge n rati o < 3 0 0 
- 
l u n g i nfiltrates > 5 0 % wit hi n 2 4 t o 4 8 h o urs 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 0 
 
3. 2. 2  Life -t hreate ni n g C O VI D- 1 9 is defi ne d as o ne or m ore of t he f oll o wi n g: 
- 
res pirat or y fail ure 
- 
se ptic s h oc k 
- 
m ulti ple or ga n d ysf u ncti o n or fail ure 
 
3. 2. 3  Wei g h t less t ha n 4 5 k g. 
 
3. 2. 4  Pre g na nt or breast -fee di n g fe males  
 
3. 2. 5  S u bjects o n dial ysis  or wit h creati ni ne cleara nce < 4 5 ml/ mi n  
 
3. 2. 6  E xisti n g D MI D T o xicit y Scale f or Deter mi ni n g Se verit y of A d verse E ve nts gra de 3 or greater 
he patic fail ure   
 
3. 2. 7  Pre vi o usl y d oc u me nte d m o derate or se vere  reti n o pat h y or mac ular de ge nerati o n 
 
3. 2. 8  U nc o ntr olle d Seiz ure dis or der  
 
 
3. 2. 9  K n o w n aller g y t o a rte misia a n n ua, artes u nate, i ver mecti n, ca m ostat  mesilate , or ot her 
a ge nts t o be use d i n t he trial.  
 
3. 2. 1 0  C urre ntl y recei vi n g a n y  st u d y me dicati o ns f or other i n dicati o ns     
 
3. 2. 1 1  C o nc urre nt use of me dicati o n t hat w o ul d ca use m o derate or se vere d ue t o dr u g- dr u g 
i nteracti o ns wit h st u d y me dicati o n.  
S pecificall y : 
•  Patie nts recei vi n g i ver mecti n ma y n ot be c o nc urre ntl y ta ki n g str o n g 
C Y P 3 A 4/ A B C B 1 i n hi bit ors ( Az ole a nt if u n gals i ncl u di n g v oric o naz ole, 
ket oc o naz ole, itrac o naz ole a n d p osac o naz ole; clarit hr o m yci n , telit hr o m yci n, 
nefaz o d o ne, sa q ui na vir, dar u na vir, or l o pi na vir, etc.) 
•  Patie nts recei vi n g Arte misi a a n n u a  te a or c offee  O R artes u n ate ma y n ot be 
c urre ntl y ta ki n g str o n g i n d ucers of C Y P 2 A 6, i ncl u di n g p he n o bar bital a n d 
rifa m pi n.[ 5 9]  
 
3. 2. 1 2  Recei pt i n t he 1 2 h o urs pri or t o e nr oll me nt, or pla n ne d a d mi nistrati o n d uri n g t he 1 4- da y 
st u d y peri o d t hat treati n g cli nicia ns feel ca n n ot be s u bstit ute d f or a n ot her me dicati o n, of 
a n y of t he f oll o wi n g: a mi o dar o ne; ci meti di ne; d ofetili de; p he n o bar bital; p he n yt oi n; or 
s otal ol. 
 
3. 2. 1 3  Ca ncer patie nts recei vi n g acti ve i m m u n os u p pressi ve treat me nt ca n n ot e nr olle d u nless 
t he y are o n a treat me nt h oli da y wit h n o a nti ne o plastic treat me nt wit h  3 wee ks  of 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 1 
 
e nr oll me nt. 
 
E nr oll me nt o n ot her e x peri me ntal t hera pies f or C O VI D 1 9  
3. 2. 1 4  I na bilit y t o recei ve e nteral me dicati o ns 
 
3. 2. 1 5  Patie nts wit h ps yc hiatric ill ness/s ocial sit uati o ns t hat w o ul d li mit c o m plia nce wit h st u d y 
re q uire me nts. 
 
3. 2. 1 6  A n y ot her c o n diti o n t hat i n t he o pi ni o n of t he treati n g p h ysicia n j ustifies e xcl usi o n fr o m 
t he st u d y.  
 
3. 3  
I ncl usi o n of W o me n a n d Mi n orities 
 
NI H p olic y re q uires t hat w o me n a n d me m bers of mi n orit y gr o u ps a n d t heir s u b p o p ulati o ns be 
i ncl u de d i n all NI H-s u p p orte d bi o me dical a n d be ha vi oral researc h pr ojects i n v ol vi n g NI H-
defi ne d cli nical researc h u nless a clear a n d c o m pelli n g rati o nale a n d j ustific ati o n esta blis hes t hat 
i ncl usi o n is i na p pr o priate wit h res pect t o t he healt h of t he s u bjects or t he p ur p ose of t he researc h.    
C ost is n ot a n acce pta ble reas o n f or e xcl usi o n e xce pt w he n t he st u d y w o ul d d u plicate data fr o m 
ot her s o urces.  W o me n of c hil d beari n g p ote ntial s h o ul d n ot be r o uti nel y e xcl u de d fr o m 
partici pati o n i n cli nical researc h.  Please see 
htt p:// gra nts. ni h. g o v/ gra nts/f u n di n g/ p hs 3 9 8/ p hs 3 9 8. p df . 
 
4.  I N V E S TI G A T O R R E Q UI R E M E N T S A N D R E GI S T R A TI O N P R O C E D U R E S 
 
4. 1  
I n vesti g at or a n d Rese arc h Ass oci ate Re gistr ati o n wit h M C C  
 
All i n vesti gat ors m ust be q ualifie d b y e d ucati o n, trai ni n g a n d e x perie nce t o ass u me 
res p o nsi bilit y f or t he pr o per c o n d uct of h u ma n s u bject researc h.  I n vesti gat ors are res p o nsi ble f or 
bei n g a ble t o pr o vi de e vi de nce of s uc h q ualificati o ns t hr o u g h u p- t o-date  c urric ul u m vitae a n d/ or 
ot her rele va nt d oc u me ntati o n a n d trai ni n g per i nstit uti o nal, state a n d fe deral g ui deli nes.  All 
i n vesti gat ors c o n d ucti n g M C C trials will c o m plete all re q uisite trai ni n g a n d re gistrati o ns per 
M C C S O Ps.  
 
4. 2  
Cli nic al Tri al Re gistr ati o n wit h cli nic altri als. g o v a n d rele ase of tri al res ults  
 
C o ntact t he M C C - C R O Re g ulat or y u nit at mccre g @ u k y.e d u if y o u nee d assista nce i n c o m pleti n g 
y o ur cli nicaltrials. g o v re gistrati o n . Res ults will be rele ase d o n cli nic altri als. g o v acc or di n g t he 
d at a g ui del i nes a n d re q uire me nts of cli nic altri als. g o v. 
 
4. 3  
E nr oll me nt G ui deli nes  
 
Eli gi ble patie nts will be i de ntifie d b y t he pri nci pal i n vesti gat or a n d c o-i n vesti gat ors of t his st u d y. 
P ote ntiall y eli gi ble patie nts will be scree ne d via m ulti ple testi n g sites as o utli ne d i n A p pe n di x F.  
Patie nts will be e val uate d at t he U ni versit y of Ke nt uc k y b y t he i n vesti gat ors a n d stu d y pers o n nel 
wit h o versi g ht b y t he Pri nci pal I n vesti gat or ( PI). U p o n o btai ni n g pr o per c o nse nt t o treat me nt, 
patie nts will be e nr olle d i nt o t he st u d y.   


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 2 
 
 
4. 4  
Dele g ati o n of T as ks L o g ( D T L)  
 
All M C C st u dies re q uire a Dele gati o n Tas k L o g w hic h is mai ntai ne d b y t he M C C Re g ulat or y 
U nit of t he Cli nical Researc h Office.  
I n or der t o be a d de d t o t he D T L f or a gi ve n st u d y, eac h staff me m ber m ust ha ve a p pr o priate 
trai ni n g t o c o n d uct assi g ne d d uties i ncl u di n g b ut n ot li mite d t o pr ot oc ol s pecific trai ni n g a n d 
re vie w of t he fi nal pr ot oc ol. 
 
4. 5  
I nf or me d C o nse nt 
 
T he g oal of t he i nf or me d c o nse nt pr ocess is t o pr o vi de pe o ple wit h s ufficie nt i nf or mati o n s o t he y 
ca n ma ke i nf or me d c h oices a b o ut w het her t o be gi n or c o nti n ue partici pati o n i n cli nical researc h.  
T he pr ocess i n v ol ves a d y na mic a n d c o nti n ui n g e xc ha n ge of i nf or mati o n bet wee n t he researc h 
tea m a n d t he partici pa nt t hr o u g h o ut t he researc h e x perie nce.  It i ncl u des disc ussi o n of t he st u d y's 
p ur p ose, researc h pr oce d ures, ris ks a n d p ote ntial be nefits, a n d t he v ol u ntar y nat ure of 
partici pati o n.  
 
T he i nf or me d c o nse nt d oc u me nt pr o vi des a s u m mar y of t he cli nical st u d y a n d t he i n di vi d ua l's 
ri g hts as a researc h partici pa nt.  T he d oc u me nt acts as a starti n g p oi nt f or t he necessar y e xc ha n ge 
of  i nf or mati o n  bet wee n  t he  i n vesti gat or  a n d  p ote ntial  researc h  partici pa nt.   Als o,  researc h  
partici pa nts a n d t heir fa milies ma y use t he c o nse nt d oc u me nt  as a n i nf or mati o n res o urce a n d 
refere nce t hr o u g h o ut partici pati o n i n t he trial.  T he i nf or me d c o nse nt d oc u me nt is ofte n c o nsi dere d 
t he f o u n dati o n of t he i nf or me d c o nse nt pr ocess; it d oes n ot, h o we ver, re prese nt t he e ntiret y of t he 
pr ocess.  N or is t he i nf or me d c o nse nt d oc u me nt a ris k -ma na ge me nt t o ol f or t he i n vesti gat or a n d/ or 
i nstit uti o n. 
 
T he i n vesti gat or m ust e x plai n t o eac h s u bject ( or le gall y a ut h orize d re prese ntati ve) t he nat ure of 
t he st u d y, its p ur p ose, t he pr oce d ures i n v ol ve d, t he e x pecte d d urati on, t he p ote ntial ris ks a n d 
be nefits i n v ol ve d a n d a n y disc o mf ort it ma y e ntail. Eac h s u bject m ust be i nf or me d t hat 
partici pati o n i n t he st u d y is v ol u ntar y a n d t hat he/s he ma y wit h dra w fr o m t he st u d y at a n y ti me 
a n d t hat wit h dra wal of c o nse nt will n ot affect his/ her s u bse q ue nt me dical treat me nt or 
relati o ns hi p wit h t he treati n g p h ysicia n. 
 
4. 6  
Recr uit me nt Pl a ns:  
 
I n p atie nt Recr uit me nt 
I n patie nts will be scree ne d b y t heir treati n g p h ysicia n tea m, i nf or me d of t he st u d y a n d if 
i ntereste d i n partici pati n g, will be a p pr oac he d b y st u d y staff f or re vie w of eli gi bilit y a n d 
i nf or me d c o nse nt. 
 
O ut p atie nt Recr uit me nt:  
•  I niti al st u dy prese nt ati o n: A p pe n dix D, E 
o  P h o ne or tele healt h c o ntact t o pr os pecti ve o ut patie nts w h o are bei n g referre d f or testi n g 
at t he U ni versit y of Ke nt uc k y 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 3 
 
 Prescree ni n g fr o m scree ni n g lists (secti o n 4. 5. 3)  
 Prese ntati o n of st u d y t o patie nt 
 Assess me nt of patie nt i nterest i n partici pati o n  
 Directi n g i ntereste d patie nts t o Researc h Desi g nate d Cli nic  or dri ve -t hr o u g h 
o  O R, wal k i n patie nt prese nti n g t o Resea rc h Desi g nate d Cli nic 
o  O R t o a tele healt h c o nse nt c o nfere nce  
 
•  Rese arc h Desi g n ate d Cli nic: U ni versit y of Ke nt uc k y a m b ulat or y care cli nics t hat are: 
o  Desi g nate d f or testi n g a n d ma na ge me nt of C O VI D- 1 9 a n d its c o m plicati o ns 
o  Pr o vi des testi n g, e val uati o n, a n d tre at me nt site a d heri n g t o c urre nt C D C a n d U ni versit y 
of Ke nt uc k y C O VI D- 1 9 g ui deli nes f or t he pr o visi o n of a m b ulat or y care  
o  I nte n de d t o e na ble recr uit me nt a n d partici pati o n i n researc h st u dies 
o  Has t he a bilit y t o o btai n t he nas o p har y n geal s wa bs, bl o o d sa m ples, electr ocar di o gra ms 
( E K Gs), a n d a d diti o nal st u d y relate d e val uati o ns re q uire d f or safet y/t olera bilit y a n d 
o utc o mes m o nit ori n g ass ociate d wit h t his st u d y 
 
•  St u dy i nt ake pr oce d ures: A p pe n dix F  
o  Researc h Desi g nate d Cli nic prese nts st u d y a n d o btai ns eit her c o nse nt or decli ne t o 
partici pate   
 E nr oll c o nse nti n g patie nts i n st u d y 
 Pr o vi de decli ni n g patie nts f ull sc o pe of r o uti ne care f or C O VI D- 1 9 patie nts 
 
4. 7  
P atie nt Scree ni n g  O pti o ns   
 
A ll i n di vi d uals w h o are teste d f or C O VI D -1 9, via a  dri ve t hr o u g h testi n g facility of t he 
U ni versit y of Ke nt uc k y, ot her testi n g sites sa ncti o ne d b y t he Ke nt uc k y De part me nt of Healt h, 
a n y o ut patie nt cli nic ass ociate d wit h U K H C, or a d mitte d t o U K H C i n patie nt h os pitals  will be 
eli gi ble f or scree ni n g .  If a scree ni n g c o nse nt is use d, i n di vid uals willi n g t o be scree ne d will 
c o nse nt t o t he f oll o wi n g: 
 
1)  
A gree t o all o w st u d y staff t o re vie w cli nical C O VI D 1 9 test res ults, baseli ne 
eli gi bilit y, la bs, via me dical rec or ds re vie w  
2)  
A gree t o be re-c o ntacte d f or st u d y partici pati o n a n d f ut ure c o ntact f or p ossi ble 
plas ma d o n or stat us. 
 
Researc h staff will re gister scree ne d patie nts i nt o a pass w or d pr otecte d Re d Ca p data base.   
 
Scree ni n g c a n be d o ne vi a o ne of t he f oll o wi n g w a ys: 
 
4. 7. 1  Face -t o-face scree ni n g o utsi de of cli nic or i n patie nt (i.e. dri ve t hr o u g h test facilit y, 
n ursi n g h o me setti n g, etc.).  I n t his setti n g, patie nts will be gi ve n a scree ni n g c o nse nt. 
 
4. 7. 2  Re m ote scree ni n g via referral fr o m t he U ni versit y of Ke nt uc k y o ut patie nt C O VI D - 1 9 
m o nit ori n g pr o gra ms, i ncl u di n g t he Get Well L o o p (a n a ut o mate d patie nt h ealt h 
m o nit ori n g t o ol, A p pe n di x E), ot her testi n g s yste ms or t hr o u g h p h o ne or tele healt h 
mec ha nis ms, w het her ce ntralize d or i n ass ociati o n wit h s pecific cli nics or cli nical 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 4 
 
e ntities, will be eli gi ble t o be as ke d if t he y are i ntereste d i n e nr oll me nt i n part ici pati n g i n 
researc h a n d will be electr o nicall y c o nse nte d via Re d Ca p a n d will be referre d t o researc h 
desi g nate d sites f or treat me nt c o nse nt a n d e val uati o n as a p pr o priate.  
 
4. 7. 3  Wai ver of c o nse nt f or scree ni n g – T he st u d y tea m will be pr o vi de d a list of all p e o ple 
testi n g p ositi ve f or C O VI D- 1 9 b y t he U ni versit y of Ke nt uc k y o ut patie nt C O VI D- 1 9 
m o nit ori n g pr o gra m  w h o ha ve a gree d t o be c o ntacte d f or t his researc h st u d y. Researc h 
staff will re vie w t his list of s u bjects, scree n f or t he hi g h ris k cate g ories w hic h w oul d 
ma ke t he m eli gi ble  a n d  c o ntact t he patie nt a n d offer partici pati o n i n t he trial via re m ote 
mea ns.   T h ose t hat meet e ntr y criteria, a n d a gree t o partici pate will t he n ha ve a n i nf or me d 
c o nse nt c o nfere nce wit h t he PI or c o -I, a C R A electr o nicall y (re m otel y, or i n pers o n) a n d 
e-si g n t he treat me nt c o nse nt via re m ote Re d Ca p c o nse nt pr ocess.  T he y will t he n be 
directe d t o t he researc h cli nic f or s peci me n c ollecti o n a n d cli nic visit.  
 
4. 7. 4  Direct scree ni n g  – Patie nt’s  treati n g p h ysicia n will be a p pr oac he d re gar di n g eli gi bilit y 
a n d a p pr o priate ness f or partici pati o n i n t his trial.   
  
4. 7. 5  Face -t o-face scree ni n g o utsi de of cli nic or i n patie nt will occ ur at t h ose testi n g sites w here 
pe o ple ca n be a p pr oac he d f or p ote ntial partici pati o n b ut ca n n ot be f ull y assesse d f or 
eli gi bilit y.  I n t hese cases, a scree ni n g c o nse nt will be use d  
 
4. 8  
C o nse nt t o Tre at me nt  
 
O nce a patie nt meets eli gi bilit y, a f or mal c o nse nt c o nfere nce will be u n derta ke n b y o ne of t he 
mea ns liste d bel o w.  
 
4. 8. 1  I n- pers o n c o nse nt: 
 
•  Researc h staff si g n t heir p orti o n of t he c o nse nt a n d t he c o nse nt f or m is gi ve n t o cli nical 
staff w h o deli ver t he c o nse nt t o t he patie nt as part of t heir cli nical d uties. 
•  Researc h staff will c o ntact t he s u bject or le gall y a ut h orize d re prese ntati ves (L A R ) b y 
tele p h o ne or vi de o p h o ne ( met h o d dictate d b y i nstit uti o nal p olic y) t o ha ve t he i nf or me d 
c o nse nt c o n versati o n. T his ste p c o nfir ms s u bject/ L A R i de ntity . 
•  If t he s u bject or L A R c o nse nts: 
o  S u bject or L A R si g ns t he c o nse nt f or m a n d t his si g nat ure is wit nesse d b y t w o 
i n di vi d uals w h o d oc u me nt t he si g ni n g of t he c o nse nt o n a pa per attestati o n f or m 
o utsi de t he r o o m.  
O R  
o  A pict ure of t he si g ne d c o nse nt is ma de, a n d e maile d t o t he st u d y staff. 
•  T he s u bject/ L A R retai ns t he c o nse nt f or m, a n d t he si g ne d attestati o n of c o nse nt or c o p y 
of t he p h ot o gra p h is st ore d i n t he researc h staff rec or ds. N o c o p y of t he c o nse nt is st ore d 
d ue t o t he p ote ntial f or tra ns missi o n of C O VI D 1 9 vir us 
 
4. 8. 2  Electr o nic C o nse nti n g 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 5 
 
•  Researc h staff e mail t he c o nse nt t o t he patie nt or L A R.  If t he patie nt or L A R is offsite, a 
sca n of t he c o nse nt f or m ca n be e maile d, fa xe d, or ot her wise electr o nicall y tra nsferre d t o 
t he L A R ( met h o d dictate d b y i nstit uti o nal p olic y) 
•  Researc h staff will c o ntact t he s u bject or L A R b y tele p h o ne or vi de o p h o ne ( met h o d 
dictate d b y i ns tit uti o nal p olic y) t o ha ve t he i nf or me d c o nse nt c o n versati o n. T his ste p 
c o nfir ms s u bject/ L A R i de ntity . 
o  If t he s u bject or L A R c o nse nts a R E D C A P s ur ve y l i n k ca n be se nt t o t heir 
pers o nal de vice a n d  t he e-c o nse nt Re d Ca p si g nat ure pr ocess is c o m plete d  a n d 
se nt t o st u d y-s pecific Re d Ca p st ora ge w here t he PI will c o-si g n t he f or m. T his 
f or m als o i n dicates t he na me of t he st u d y tea m me m ber t hat was i n v ol ve d i n t he 
c o nse nt pr ocess.  
o  If usi n g a st u d y- pr o vi de d de vice, t he s u bject rea ds t he c o nse nt a n d f oll o ws t he 
pr o m pts i n Re d Ca p a n d t he si g ne d c o nse nt is electr o nicall y tra ns mitte d t o t he 
st u d y-s pecific Re d Ca p st ora ge w here t he PI will c o-si g n t he f or m.  T his f or m als o 
i n dicates t he na me of t he st u d y tea m me m ber t hat was i n v ol ve d i n t he c o nse nt 
pr ocess. T he de vice is t he n disi nfecte d acc or di n g t o l ocal i nstit uti o nal practices.  
•  T he s u bject/ L A R re cei ves a n electr o nic c o p y of t he c o nse nt f or m t o t he e mail pr o vi de d, 
a n d t he e- si g ne d c o nse nt is st ore d i n Re d Ca p t he researc h staff rec or ds. 
 
4. 8. 3  Ver bal c o nse nt 
 
Beca use of t he nat ure of t his viral disease a n d t he p ossi bilit y of tra ns missi o n t hr o u g h direct 
c o ntact wit h t he s u bject, ver bal c o nse nt ma y als o be gi ve n b y t he s u bject if wit nesse d a n d 
c o nfir me d b y t w o st u d y staff. T he ver bal c o nse nt will be d oc u me nte d o n t he c o nse nt f or m a n d 
si g ne d b y t he t w o wit nesses.  
 
If t he s u bject ca n n ot rea d or si g n t he d oc u me nts, oral prese ntati o n ma y be ma de or si g nat ure 
gi ve n b y t he s u bject’s le gall y a p p oi nte d re prese ntati ve, if wit nesse d b y t w o pe o ple a n d 
d oc u me nti n g t hat t he patie nt c o ul d n ot rea d or si g n t he d oc u me nts. N o patie nt ca n e nter t he st u d y 
bef ore his/ her i nf or me d c o nse nt has bee n o btai ne d.  T he i nf or me d c o nse nt f or m is c o nsi dere d t o 
be part of t he pr ot oc ol, a n d m ust be s u b mitte d b y t he i n vesti gat or wit h t he pr ot oc ol at t he ti me of 
I R B re vie w. 
 
 
4. 9  
 P atie nt Re gistr ati o n t o Tre at me nt  
 
T o re gister a patie nt, t he f oll o wi n g i nf or mati o n  s h o ul d be re vie we d b y t he cli nical researc h n urse 
( C R N) / cli nical researc h ass ociate ( C R A) wit h t he st u d y p h ysicia n per M C C S O Ps  t o c o nfir m 
eli gi bilit y: 
•  C o p y of C O VI D 1 9  testi n g res ults 
•  M o bile E K G traci n g ( o ut patie nts) or sta n dar d E K G (i n patie nts) wit hi n 5 da ys of 
re gistrati o n t o assess Q Tc i nter val  
•  E li gi bilit y la bs, as well as c orrelati ve la bs t o be dra w n  
•  Eli gi bilit y C hec klist  
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 6 
 
O nce eli gi bilit y is c o nfir me d, t he C R N/ C R A  will c o m plete s u bject re gistrati o n i n t he O n C ore 
data base  ( mi ni m u m data f o ot pri nt) f or ra n d o mizati o n a n d c o m plete st u d y -re q uire d Re d Ca p data 
f or ms. T o c o m plete t he re gistrati o n pr ocess, t he C R N/ C R A  will : 
•  assi g n a patie nt st u d y n u m ber 
•  re gister t he patie nt o n t he st u d y i n O n C ore 
•  recei ve t he a ut o mate d treat me nt ar m assi g n me nt   
•  se n d a n e mail or ot her c o m m u nicati o n t o t he st u d y tea m of ar m  assi g n me nts. 
 
If a patie nt is dee me d i neli gi ble f or treat me nt t heir s peci me ns will be retai ne d i n t he C O VI D 1 9 
BI O B A N K  if t he s u bject has i n dicate d a gree me nt t o s peci me n c ollecti o n a n d l o n g-ter m st ora ge 
i n t he c o nse nt f or m. 
 
At t he Da y 1 visit  or i n patie nt t he f oll o wi n g will be c o m plete d 
1)  Si g n tre at me nt i nf or me d c o nse nt ( u nless pre vi ousl y e- c o nse nte d as a b o ve)   
2)  U n der g o bl o o d testi n g f or eli gi bilit y (i n s u bjects w h o ha ve n ot ha d assess me nt of 
scree ni n g la bs wit hi n t he last 3 0 da ys will re q uire bl o o d dra w) 
3)  C o m plete a n eli gi bilit y q uesti o n naire (a ge, c o nc urre nt diseases, c urre nt me dicati o ns, 
c o ntact i nf or mati o n) 
4)  U n der g o a m o bile E K G or sta n dar d E K G traci n g t o assess Q Tc i nter val ( wit hi n 5 da ys 
of re gistrati o n)  
5)  Distri b ute me dicati o ns, pill diar y , a n d i nstr ucti o ns 
6)  Baseli ne c orrelati ve bl o o d sa m ple 
7)  S p ut u m sa m ple , wit h O P s wa b (alter nati ve, if n o s p ut u m a vaila ble) 
8)  Sali va sa m ple  
9)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
1 0)  Li mite d vis ual p h ysical e xa m u nless a m ore c o m plete e xa m is cli nicall y i n dicate d.  
 
Da y 3  or 4 p h o ne call t o assess cli nical stat us a n d elicit c o ncer ns or q uesti o ns.  
 
Da y 7 tele healt h ( +/- 4 da ys) is re q uire d f or all patie nts t o assess t o xicit y.  If a s u bject has a 
sta n dar d of care tele healt h visit d uri n g t his peri o d, t his is als o a n acce pta ble t o xicit y assess me nt.  
 
Da y 1 0 or 1 1 p h o ne call t o assess cli nical stat us a n d elicit c o ncer ns or q uesti o ns  
 
Da y 1 4 ( +/- 4 da ys) visit  will als o be c o m plete d i n cli nic or i n patie nt h os pital . 
1)  U n der g o bl o o d testi n g f or t o xicit y 
2)  C ollecti o n of me dicati o ns, pill diar y a n d i nstr ucti o ns 
3)  M o bile E K G traci n g ( o ut patie nts) or sta n dar d E K G (i n patie nts) t o assess Q Tc i nter val  
4)  C orrelati ve b l o o d sa m ple 
5)  S p ut u m sa m ple , wit h O P s wa b  (alter nati ve, if n o s p ut u m a vaila ble) 
6)  Sali va sa m ple ( o pti o nal)  
7)  Nas o p har y n geal s wa b ( o pti o nal a n d if i n dicate d f or sta n dar d of care) * 
8)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
9)  T o xicit y assess me nt via tele healt h or p h o ne call ( +/ - 4 da ys) 
 
Da y 2 8 ( +/- 4 da ys) visit will als o be c o m plete d i n cli nic or i n patie nt h os pital . 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 7 
 
1)  C orrelati ve bl o o d sa m ple  
2)  S p ut u m sa m ple , wit h O P s wa b  (alter nati ve, if n o s p ut u m a vaila ble) 
3)  Sali va sa m ple  ( o pti o nal) 
4)  Nas o p har y n geal s wa b ( o pti o nal a n d if i n dicate d f or sta n dar d of care) * 
5)  Ser ol o g y testi n g *  
6)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
7)  T o xicit y assess me nt via tele healt h or p h o ne call ( +/ - 4 da ys) 
 
Da y 4 0 ( +/- 4 da ys) visit . If ser ol o g y testi n g is ne gati ve or viral l oa d re mai ns p ositi ve, patie nts 
will be re q ueste d t o ret ur n f or a Da y 4 0 visit ( o pti o nal) will als o be c o m plete d via dri ve t hr o u g h 
( preferre d), cli nic or i n patie nt h os pital. 
1)  C orrel ati ve bl o o d sa m ple  
2)  S p ut u m sa m ple , wit h O P s wa b  (alter nati ve, if n o s p ut u m a vaila ble) 
3)  Sali va sa m ple  ( o pti o nal) 
4)  Nas o p har y n geal s wa b ( o pti o nal a n d if i n dicate d f or sta n dar d of care) *  
5)  Ser ol o g y testi n g ( o pti o nal a n d if i n dicate d f or sta n dar d of care) *  
6)  C O VI D -1 9 or di nal scale assess me nt  ( See A p pe n di x B) 
* T hese are c o nsi dere d sta n dar d of care tests 
 
4. 1 0  Ge ner al G ui deli nes  
 
F oll o wi n g re gistrati o n, patie nts s h o ul d be gi n pr ot oc ol treat me nt wit hi n 7 da ys.  Iss ues t hat w o ul d 
ca use treat me nt dela ys s h o ul d be disc usse d wit h t he Pri nci pal I n vesti gat or.  If a patie nt d oes n ot 
recei ve pr ot oc ol t hera p y f oll o wi n g re gistrati o n, t he PI a n d t he statisticia n m ust be c o ns ulte d as 
s o o n as p ossi ble.  
 
 
5.  BI O M A R K E R, C O R R E L A TI V E , A N D S P E CI A L S T U DI E S   
 
5. 1  
S u m m ar y T a ble f or S peci me n C ollecti o n  
 
Ti me P oi nt  
S peci me n  
Se n d S peci me ns T o:  
Arc hi v al  
 
•  Disc ar de d tiss ue or bl o o d s a m ples fr o m 
ori gi n al C O VI D 1 9 testi n g  
•  Resi d u als fr o m a ny of t he rese arc h 
s a m ples c ollecte d bel o w 
Ce nter f or Cli nic al a n d 
Tr a nsl ati o n al Scie nce 
( C C T S) C O VI D- 1 9 
Rese arc h Re gistry a n d 
S peci me n B a nk ( C R R S B)  
B aseli ne  –  D a y 1  
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes   
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
Bi os peci me n Pr oc ure me nt 
a n d Tr a nsl ati o n al P at h ol o gy 
S h are d Res o urce F acility 
( B P T P S R F) or C C T S 
C R R S B   


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 8 
 
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al)  
D ay 1 4 ( +  / - 4  d ay)  
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes   
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al ) 
B P T P S R F  or C C T S C R R S B  
D ay 2 8 ( +/- 4  d ay s) 
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes 
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al ) 
B P T P S R F  or C C T S C R R S B  
D ay 4 0 ( +/- 4  d ay s) 
 
•  1 0 m L a n d 6 m L bl o o d i n E D T A ( p ur ple 
t o p) t u bes f or a nti b o dy testi n g, 
pr oc alcit o ni n, C R P a n d cyt oki nes   
•  5 m L bl o o d i n A C D ( yell o w t o p) t u be f or 
pl atelet f u ncti o n ass ays ( o pti o n al)  
•  8 m L bl o o d i n C P T t u be ( o pti o n al)   
•  S p ut u m s a m ple ( M a n d at ory) or O P s w a b 
( alter n ative, if s p ut u m is u n av ail a ble) 
•  1 ml of s aliv a ( o pti o n al ) 
B P T P S R F  or C C T S C R R S B  
 
 
5. 2  
S peci me n Pr oc ure me nt Kits a n d Sc he d uli n g  
 
5. 2. 1  S peci me n Pr oc ure me nt Kits  
 
S peci me n pr oc ure me nt kits will be s u p plie d b y t he Bi os peci me n Pr oc ure me nt a n d Tra nslati o nal 
Pat h ol o g y S hare d Res o urce Facilit y ( B P T P S R F).   
 
5. 3  
S peci me n C ollecti o n a n d Pr ocessi n g  
 
Resi d u al Cli nic al  S a m ples  ( bl o o d, s p ut u m, sali va, nas o p har y n geal a n d or o p har y n geal s wa b 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
1 9 
 
sa m ples): Resi d ual cli nical sa m ples will i ncl u de ser u m a n d plas ma ori gi nall y c ollecte d i n E D T A, 
citrate d or he pari nize d t u bes a n d s u bse q ue ntl y st ore d at - 2 0 0C i n 5 ml p o ur- off t u bes. 
S u b se q ue ntl y, t hese sa m ples will be tra nsferre d t o t he Mar ke y Ca ncer Ce nter Bi os peci me n 
Pr oc ure me nt a n d Tra nslati o nal Pat h ol o g y S hare d Res o urce Facilit y ( B P T P) or t he Ce nter f or 
Cli nical a n d Tra nslati o nal Scie nce ( C C T S) C O VI D -1 9 Researc h Re gistr y a n d S peci me n  Ba n k . 
B P T P  or C C T S  staff will l o g, a n d la bel a n d st ore t he resi d ual cli nical plas ma a n d ser u m 
s peci me ns at - 8 00C or l o wer. U p per res pirat or y tract sa m ples will i ncl u de resi d ual 
nas o p har y n geal a n d or o p har y n geal s wa b s peci me ns st ore d i n viral tra ns p ort me di a ( V T M) a n d 
i nitiall y fr oze n at - 7 00C. After tra ns p ort t o t he B P T P, t he staff will l o g, la bel a n d st ore t he 
s peci me ns at - 8 00C or l o wer.  
 
Rese arc h Peri p her al Bl o o d S a m ples  f or Pr oc alcit o ni n, D- Di mer , C yt o ki nes, 
Ser oc o n versi o n , a n d Pl atelet F u ncti o n: O ne 1 0- m L a n d o ne 6- m L E D T A ( p ur ple t o p) t u bes, 
o ne 5 m L bl o o d i n A C D ( yell o w t o p) t u be a n d o ne 8 m L bl o o d i n C P T t u be ( o pti o nal)  of bl o o d 
will be dra w n a n d i m me diatel y deli vere d  t o t he Mar ke y B P T P-S R F la b  or t he C C T S  C O VI D - 1 9 
Researc h Re gistr y a n d S peci me n Ba n k. E D T A a n d C P T t u bes will be p r ocesse d as s o o n as 
p ossi ble, b ut at m ost will occ ur wit hi n 2 4 h o urs of bl o o d dra w.  A C D t u bes will be deli vere d 
i m me diatel y t o t he W hite heart la b (see bel o w).  Bi o ba n k staff will freeze a 1 - m L ali q u ot of 
w h ole bl o o d, t he n ce ntrif u ge t he re mai n der at ~ 1, 2 0 0 R C F f or 1 2 mi n utes t o se parate a n d c ollect 
plas ma a n d b uff y c oat. Sa m ples will be l o g ge d a n d la bele d a n d ali q u ote d a n d st ore d fr oze n at –
8 0 0C or l o wer. Deli ver y a n d recei pt of refri gerate d bl o o d sa m ples will occ ur M o n da y t hr o u g h 
Fri da y. 
 
Rese arc h Or o p h ar y n ge al ( O P) , f or Vir al L o a d: O ne s wa b sa m ple will be c ollecte d per patie nt 
f oll o wi n g sta n dar d pr oce d ure at eac h st u d y ti me p oi nt, i m me diatel y place d i n viral tra ns p ort 
me dia a n d refri gerate d or st ore d at -8 0 0C or l o wer. Deli veries a n d recei pt of fr oze n or 
refri gerate d sa m ples will occ ur M o n da y t hr o u g h Fri da y. 
 
Rese arc h S p ut u m S a m ples  f or Vir al L o a d: O ne s p ut u m sa m ple per patie nt at eac h st u d y ti me 
p oi nt will be c ollecte d f oll o wi n g sta n dar d pr ot oc ol. T he s peci me ns will be deli vere d i m me diatel y 
t o t he B P T P la b. Sa m ples will be l o g ge d a n d la bele d a n d st ore d at - 8 00C or l o wer.  
 
Rese arc h S ali v a S a m ples:  O ne o pti o nal sali va sa m ple per patie nt at eac h st u d y ti me p oi nt will 
be c ollecte d f oll o wi n g sta n dar d pr ot oc ol. T he s peci me ns will be c ollecte d i n a sta n dar dize d kit 
a n d hel d at 4 0C u ntil deli ver y t o t he B P T P la b. Sa m ples will be l o g ge d a n d la bele d a n d deli vere d 
t o t he W o o d war d La b. 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 0 
 
 
 
Researc h s peci me n pr ocessi n g a n d deli ver y al g orit h m 
 
5. 4  
S hi p pi n g/ Dis pe nsi n g of S peci me ns  
Sa m ples will be tra ns p orte d t o t he M C C B P T P S R F or t he C C T S C O VI D -1 9 Researc h Re gistr y 
a n d S peci me n Ba n k f or pr ocessi n g a n d tra ns p ort t o t he a p pr o priate la bs as a b o ve.   
 
6.  T R E A T M E N T P L A N  
 
S u bjects will be a p pr oac he d at t he ti me of i nitial C O VI D- 1 9 testi n g or wit hi n 7 da ys of a p ositi ve 
test. Pri or t o a n y st u d y-re q uire d tests, s u bjects m ust first pr o vi de writte n i nf or me d c o nse nt t o 
partici pate i n t his st u d y.   
 
6. 1  
A ge nt A d mi nistr ati o n  
 
T he C U R E Allia nce  Dr u g Steeri n g C o m mittee  will ser ve as t he dr u g selecti o n c o m mittee t o 
i de ntif y t he a p pr o priate ne w dr u gs f or eac h ne w ar m of t his cli nical trial . Treat me nt will be 
a d mi nistere d o n a n o ut patie nt  or i n patie nt basis  pr o vi de d t hat e ntr y criteria are met. If e mer gi n g 
data i n dicates f utilit y of a me dicati o n i n o ne or m ore ar ms of o ur st u d y, a n d was teste d i n a 
si milar patie nt p o p ulati o n i n a ra n d o mize d cli nical trial or trials, t he st u d y dr u g selecti o n 
c o m mittee ma y rec o m me n d re m o val of t hat dr u g treat me nt ar m f or f utilit y wit h a p pr o val of t he 
st u d y tea m. O nce a f utilit y e n d p oi nt is met i n a n ar m, we will re place t hat ar m wit h t he ne xt 
a p pr o priate pr o p ose d ar m wit h a p pr o val of t he C U R E Allia nce Dr u g Steeri n g C o m mittee. 
All s u bjects recei ve st a n d ar d s u p p orti ve tre at me nt t hr o u g h o ut t heir i nfecti o n, w het her 
o ut p atie nt or d uri n g i n p a tie nt h os pit aliz ati o n.  Re p orte d a d verse e ve nts a n d p ote ntial ris ks are 
descri be d i n Secti o n 1 0.   
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 1 
 
Tr eat me nt re gi me ns will be e val uate d  a n d n o vel a ge nts selecte d b y t he steeri n g c o m mittee.  
S h o ul d dr u g s u p pl y bec o me u na vaila ble t hat ar m w o ul d pa use u ntil dr u g s u p pl y is a vaila ble. 
 
Re gi me n Descri pti o n - Ar m C  
A ge nt  
F or m ul ati o n 
Stre n gt h  
D aily  
D ose  
R o ute  
Sc he d ule  
I ver mecti n 
3 m g ta blet  
1 2 -1 5  m g  
Oral  
Wei g ht < 7 5 k g : 4 ta b s o n Da ys 1 a n d 2, 
( 1 2 m g t otal dail y d ose)  
Wei g ht > 7 5 k g: 5 ta b s o n Da ys 1 a n d 2, 
( 1 5 m g t otal dail y d ose)  
 
Re gi me n Descri pti o n - Ar m D  
A ge nt  
F or m ul ati o n 
Stre n gt h  
D aily  
D ose  
R o ute  
Sc he d ule  
Ca m ostat Mesilate   
1 0 0 m g ta blet  
6 0 0 m g  
Oral  
2  ta b TI D after a meal  ( 6 0 0 m g t otal 
dail y d ose) Da ys 1 -1 4  
 
Re gi me n Descri pti o n - Ar m E  
A ge nt  
F or m ul ati o n  
Stre n gt h  
D aily  
D ose  
R o ute  
Sc he d ule  
Arte misia  a n n ua tea 
or c offee  
Decaf c offee 
4 5 0 m g per p o d 
Tea 2 2 5 m g per 
ba g  
1 3 5 0 m g  
Oral  
O ne 8 oz bre we d tea (t w o ba gs) or o ne 
c offee p o d TI D Da ys 1- 1 4 
 
Re gi me n Descri pti o n - Ar m F  
A ge nt  
F or m ul ati o n 
Stre n gt h  
D ail y  
D ose  
R o ute  
Sc he d ule  
Artes u n ate  
1 0 0 m g  
2 0 0 m g  
Oral  
T w o ta bs o nce da y ( 2 0 0 m g t otal) Da ys 
1 -1 4  
 
 
Patie nts will be assi g ne d t o a treat me nt ar m acc or di n g t o t he ra n d o mizati o n pr ocess descri be d i n 
Secti o n 9 of t his pr ot oc ol  
 
Si nce t here are n o safet y data f or t he me dicati o n s t o be e val uate d o n all ar ms of t his st u d y i n t he 
mil d t o m o derate S A R S -C o V -2 i nfecte d p o p ulati o n, t he first si x patie nts o n eac h ar m will be 
e val uate d f or a n y gra de 3 or hi g her he mat ol o gic or n o n- he mat ol o gic t o xicit y f or 1 4 da ys .  Patie nts 
c o mi n g off st u d y bef ore t he first 1 4 da ys  f or reas o ns ot her t ha n t o xicit y will be re place d. If t w o or 
m ore of t he si x patie nts i n t his ar m of t he st u d y de vel o p u nacce pta ble t o xicit y, t he treat me nt f or 
t hat ar m w o ul d be c o nsi dere d u nsafe a n d st o p pe d. Patie nts e x hi biti n g ra pi d pr o gressi o n of C O VI D-
1 9 s y m pt o mat ol o g y re q uiri n g i nte nsi ve care h os pitalizati o n or i nt u bati o n will c o me off st u d y a n d 
will be c o nsi dere d fail ures i n ter ms as per t he pri mar y e n d p oi nts of t he st u d y b ut n or f or safet y a n d 
will be re place d if t hese cases occ urre d d uri n g t he p hase 1 p orti o n of t he st u d y. 
 
O nce t he p hase 1 p orti o n safet y r u n-i n has c o ncl u de d, t hat ar m will be o pe ne d f or p hase II accr ual.  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 2 
 
P atie nts will be assi g ne d t o eac h ar m i n c o h orts of t hree at a ti me u ntil accr ual n u m bers f or eac h 
ar m are f ulfille d or disc o nti n ue d d ue t o safet y c o ncer ns occ urri n g be y o n d t he P hase 1 p orti o n.  
M o nt hl y p h o ne c o nfere nces a m o n g i n vesti gat ors d uri n g e nr oll me nt will ta ke place.   
 
Patie nts will u n der g o baseli ne m o bile E K G or sta n dar d E K G t o e val uate Q Tc i nter val o n Da y  1 
( or wit hi n 5 da ys of re gistrati o n if i n patie nt) a n d a re peat E K G at Da y 14 ( +/- 4 da ys).  A n y C hest 
X- ra y or C T sca n of t he c hest t hat is perf or me d f or r o uti ne care will be re vie we d b y t he PI f or 
eli gi bilit y a n d rec or de d o n case re p ort f or ms.  N O T E: if a patie nt de vel o ps a m y ocar dial i nfarcti o n  
or gra de 3 or 4 car diac arr yt h mia w hile o n t he 1 4 da ys of dr u g, t he y sh o ul d be i m me diatel y  ta ke n 
off st u d y me dicati o n a n d recei ve sta n dar d of care treat me nt per t heir treati n g p h ysicia n. 
 
Patie nts will be f oll o we d f or cli nical o utc o mes b y p h o ne c o ntact eac h wee k a n d h os pitalizati o ns, 
a n d all c o m plicati o ns will be rec or de d o n  a d verse e ve nt case re p ort f or ms.  
 
6. 2  
Defi niti o n of D ose -Li miti n g T o xicit y ( D L T) f or p h ase I r u n i n p orti o ns of t his 
pr ot oc ol  
 
A D L T is defi ne d as a n y of t he bel o w treat me nt e mer ge nt t o xicities wit h attri b uti o n  of 
defi nitel y, pr o ba bl y or p ossi bl y relate d t o o ne or m ore of t he st u d y dr u gs t hat occ ur d uri n g t he 
first 1 4 da ys of st u d y treat me nt.   T o xicities t hat occ ur after t he 1 4 da y treat me nt peri o d will be 
re p orte d t hr o u g h a d verse e ve nt re p orti n g o utli ne d i n secti o n 1 0. 0, b ut will n ot be c o u nte d as 
D L Ts .    
 
• 
G r a de 3 or hi g her n o n - he m at ol o gic or n o n -he m at ol o gic  t o xicit y at le ast p ossi bl y, 
pr o b a bl y or defi nitel y rel ate d t o st u d y me dic ati o n or pr oce d ures,  per  D MI D 
T o xicit y Sc ale f or Deter mi ni n g Se verit y of A d verse E ve nts  
 
6. 3  
D ur ati o n of T her a p y  
 
I n t he a bse nce of treat me nt dela ys d ue t o a d verse e ve nt(s), treat me nt is gi ve n u ntil o ne of t he 
f oll o wi n g criteria a p plies: 
 
•  
I nterc urre nt ill ness t hat pre ve nts f urt her a d mi nistrati o n of treat me nt 
 
•  
U nacce pta ble a d verse e ve nt(s)  
 
•  
Patie nt deci des t o wit h dra w fr o m t he st u d y  
 
•  
Ge neral or s pecific c ha n ges i n t he patie nt's c o n diti o n re n der t he patie nt u nacce pta ble f or 
f urt her treat me nt i n t he j u d g me nt of t he i n vesti gat or 
 
•  
Patie nt n o n -c o m plia nce 
 
•  
Pre g na nc y 
 
 
•  
T he dr u g ma n ufact urer ca n n o l o n ger pr o vi de t he st u d y a ge nt 
 
•  
A d missi o n t o t he I nte nsi ve Care U nit a n d/ or nee d f or mec ha nical ve ntilati o n. At t his 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 3 
 
ti me, t he treati n g p h ysicia n will ha ve t he a bilit y t o c o nti n ue st u d y dr u g, disc o nti n ue 
t hera p y, place t he patie nt o n a n ot her st u d y trial, or treat t he patie nt wit h alter nati ve 
t hera pies, per t heir cli nical j u d ge me nt. At t his p oi nt, t he patie nt will be f oll o we d b y t he 
st u d y tea m t o trac k o utc o mes a n d m o nit or f or a d verse e ve nts t hat mi g ht be attri b uta ble t o 
st u d y dr u g b ut t he dr u g will be c o nsi dere d t o ha ve faile d t he pri mar y e n d p oi nt 
 
T he reas o n(s) f or pr ot oc ol t hera p y disc o nti n uati o n, t he reas o n(s) f or st u d y re m o val, a n d t he 
c orres p o n di n g dates m ust be d oc u me nte d i n t he Case Re p ort F or m ( C R F). F or clarit y, “ off 
treat me nt” is t he date w he n all me dicati o n has bee n c o m plete d (i ncl u di n g t he n or mal o bser vati o n 
peri o d) or disc o nti n ue d d ue t o o ne of t he fact ors a b o ve, a n d n o f urt her treat me nt is pla n ne d. T his 
is t he date t he patie nt has bee n officiall y ta ke n off treat me nt. “ Off st u d y” is t he date after w hic h 
n o f urt her f oll o w- u p of t he patie nt will occ ur 
 
6. 4  
D ur ati o n of F oll o w- U p   
 
Patie nts will be f oll o we d f or u p t o 4 0 da ys fr o m t he be gi n ni n g of t hera p y or u ntil deat h, 
w hic he ver occ urs first.    
 
7.  D O SI N G D E L A Y S/ D O S E M O DI FI C A TI O N S  
 
N/ A . 
 
8.  P H A R M A C E U TI C A L  I N F O R M A TI O N 
 
A list of t he a d verse e ve nts a n d p ote ntial ris ks ass ociate d wit h t he i n vesti gati o nal or c o m mercial 
a ge nts a d mi nistere d i n t his st u d y ca n be f o u n d i n Secti o n 1 0. 1. 
 
8. 1  
Dr u g Or deri n g a n d Acc o u nt a bilit y  
 
8. 1. 1  Pr oc ure me nt of me dic ati o ns:  
Prescri pti o ns f or me dicati o ns  will be writte n b y t he site PI, q ualifie d C o -I ( p h ysicia n), or treati n g 
p h ysicia n as o utli ne d i n Secti o n 6. 0.  I D S will or der a n d dis pe nse i ver mecti n, ca m ostat mesilate , 
artes u nate  a n d ot her i n vesti gati o nal a ge nts if ne w ar ms are o pe ne d  d uri n g t he treat me nt p hase of 
t his trial. Dr u g acc o u nta bilit y will be mai ntai ne d o n a Nati o nal Ca ncer I nstit ute Dr u g 
Acc o u nta bilit y Re p ort F or m ( D A R F).  Arte misia  a n n ua, a nat ural pr o d uct/ b ota nical, will be 
or dere d directl y fr o m Baes ma n Distri b ut ors.  
 
8. 1. 2  St or a ge & Dr u g Acc o u nt a bility:  
T he U ni versit y of Ke nt uc k y I n vesti gati o nal Dr u g Ser vice p har macist  will e ns ure t hat all st u d y 
dr u g is st ore d i n a sec ure d, li mite d access st ora ge area, u n der rec o m me n de d st ora ge c o n diti o ns i n 
acc or da nce wit h a p plica ble la bel i n g a n d re g ulat or y re q uire me nts a n d as pr o vi de d b y t he se parate 
st u d y dr u g acc o u nta bilit y ma n ual. U n der n o circ u msta nces s h o ul d t he i n vesti gat or or ot her site 
pers o n nel s u p pl y st u d y dr u g t o ot her i n vesti gat ors, patie nts, or cli nics. A de q uate rec or ds 
d oc u me nti n g recei pts, use, ret ur n, l oss, or ot her dis p ositi o n of st u d y pr o vi de d dr u gs m ust be 
ke pt. T he U ni versit y of Ke nt uc k y I n vesti gati o nal Dr u g Ser vice will s u p pl y dr u g acc o u nta bilit y 
f or ms t hat will be use d, or ma y a p pr o ve use of sta n dar d i nstit uti o n f or ms. Dr u g acc o u nta bilit y 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 4 
 
a n d s u p pl y or der i nstr ucti o ns a n d f or ms will be pr o vi de d i n a se parate st u d y ma n ual. T he 
acc o u nta bilit y le d gers will be mai ntai ne d t o c o ntai n c urre nt a n d acc urate i n ve nt or y rec or ds a n d 
m ust be rea dil y a vaila ble f or i ns pecti o n. U nless o t her wise a ut h orize d b y t he s p o ns or, at t he e n d 
of t he cli nical trial all dr u g s u p plies u nall ocate d or u n use d b y sites or patie nts m ust be ret ur ne d t o 
t he U ni versit y of Ke nt uc k y I n vesti gati o nal Dr u g Ser vice ( U K I D S) f or fi nal acti o ns i n 
acc or da nce wit h s p o ns or i nstr ucti o ns.  
 
T he e xce pti o n t o t his practice will be t he nat ural pr o d uct, Arte misia  a n n ua tea or c offee w hic h is 
c o m merciall y a vaila ble a n d will be s u p plie d b y Arte milife, via its distri b ut or, Baes ma n 
d istri b ut ors (see A p pe n di x H f or i nstr ucti o ns) 
 
8. 1. 3  Iver mecti n 
 
Pr oc ure me nt  
T his me dicati o n will be dis pe nse d b y I D S ser vice.  
 
F or m ul ati o n  
3 m g ta blets  
 
Pre p ar ati o n, St or a ge a n d St a bility  
Please refer t o pac ka ge i nsert f or c o m plete pre parati o n a n d dis pe nsi n g i nstr ucti o ns. 
Dis pe nse  ei g ht 3 m g ta blets (f or patie nts  < 7 5 k g); te n 3 m g ta blets (f or patie nts > 7 5 k g)  
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n  6. 1 f or s pecific a d mi nistrati o n i nstr ucti o ns.  
 
Patie nts  s h o ul d be i nstr ucte d t o ta ke: 4 ta bs o n Da ys 1 a n d 2, ( 1 2 m g t otal dail y d ose) f or wei g ht 
< 7 5 m g; or 5 ta b s o n Da ys 1 a n d 2, ( 1 5 m g t otal dail y d ose) f or wei g ht > 7 5 k g.  I ver mecti n 
s h o ul d be ta ke n o n a n e m pt y st o mac h. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: C Y P 3 A 4 a n d A B C B 1 i n hi bit ors ma y i ncrease t hera pe utic 
c o nce ntrati o ns of i ver mecti n, a v oi d c o nc urre nt use of i ver mecti n a n d str o n g C Y P 3 A 4 or A B C B 1 
i n hi bit ors 
Decrease d Effect: I ver mecti n ma y decrease t he t hera pe utic effect of B C G a n d li ve vacci nes, 
a v oi d c o nc urre nt use  
 
Her b/ N utr ace utic al I nter acti o ns : N o ne  
 
P h ar m ac oki netics  
A bs or pti o n : Well a bs or be d, a d mi nister o n e m pt y st o mac h.  Hi g h fat meal i ncrease d 
bi oa vaila bilit y 2. 5 f ol d  
Distri b uti o n: V d: 3. 1- 2. 5 L/ k g, d oes n ot cr oss bl o o d brai n barrier  
Meta b olis m: He patic via  C Y P 3 A 4 ( maj or)  
Half -life eli mi nati o n:  
Ter mi nal: 1 8 h o urs  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 5 
 
E xcreti o n: Less t ha n 1 % via feces a n d uri ne  
 
A dverse Eve nts  
C o ns ult t he pac ka ge i nsert f or t he m ost c urre nt a n d c o m plete i nf or mati o n.  
 
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %: N o ne 
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
Tac h ycar dia ( 4 %)  
Peri p heral e de ma ( 3 %)  
Dizzi ness ( 3 %)  
Diarr hea ( 2 %)  
E osi n o p hilia ( 3 %) 
Ele vati o ns i n L F Ts ( 2 %) 
 
R are k n o w n p ote nti al t o xicities, < 1 % ( Li mite d t o i m p ort a nt or life -t hre ate ni n g): 
H y per bilir u bi ne mia  
H y perse nsiti vit y 
 
Pre g na nc y: T he here is i ns ufficie nt e vi de nce t o pr o ve safet y.   Base d o n t he a ni mal a n d h u ma n 
data i ver mecti n is la bele d cate g or y C i n t he U S ( a ni mal E F D fi n di n g, b ut o nl y at d oses als o t o xic 
t o t he pre g na nt fe male).  T h e ma n ufact urer c o nsi ders it c o ntrai n dicate d i n pre g na nc y. 
8. 1. 4   C a m ost at Mesil ate  
 
Pr oc ure me nt  
T his me dicati o n will be dis pe nse d b y I D S ser vice.  
 
F or m ul ati o n  
1 0 0 m g ta blets 
 
Pre p ar ati o n, St or a ge a n d St a bility  
T a blets s h o ul d be st ore d at r o o m te m perat ure.   
 
Dis pe nse 8 4, 1 0 0 m g ta blets  
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n f or s pecific a d mi nistrati o n i nstr ucti o ns  
Patie nts s h o ul d be i nstr ucte d t o ta ke t w o 10 0 m g ta blet, t hree ti mes per da y (after meal)  Da ys 1 -
1 4. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: N o k n o w n dr u g i nteracti o ns 
  
Decrease d Effect: N o k n o w n dr u g i nteracti o ns 
  
Her b/ N utr ace utic al I nter acti o ns : N o k n o w n dr u g i nteracti o ns 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 6 
 
  
P h ar m ac oki netics  
A bs or pti o n: well a bs or be d orall y 
Distri b uti o n: N ot esta blis he d  
Meta b olis m: Meta b oli ze d t o t w o maj or meta b olites: t he car b o x ylic aci d deri ve d fr o m clea va ge of 
t he car b o xa mi de ( F O Y- 2 5 1); a n d t he car b o x ylic aci d deri ve d fr o m clea va ge of t he i nter nal 
car b o x yester ( G B A).  B ot h are ra pi dl y eli mi nate d wit h eli mi nati o n half -li ves of r o u g hl y 1 
h o ur.  F O Y -2 5 1 retai ns acti vit y a gai nst t he pr otease tar get.  
Half -life eli mi nati o n: 1 7 0 mi n utes  
Ter mi nal: N ot re p orte d  
E xcreti o n: M ost of t he s u bsta nce is e xcrete d b y 5 t o 6 h o urs after d osi n g, t hr o u g h all r o utes 
i ncl u di n g fecal, uri ne, bile, etc.  A b o ut 2 0 % of a 2 0 0 m g d ose is e xcrete d i nt o t he uri ne as G B A 
a n d a b o ut 1 % is e xcrete d as F O Y- 2 5 1 
  
A dverse Eve nts  
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %:  
N o ne re p orte d 
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
T hr o m b oc yt o pe nia 
H y p o kale mi a 
Li ver f u ncti o n a b n or malities 
Ja u n dice 
Itc hi n g or s ki n er u pti o n/ras h  
Ne p hr olit hiasis  
Dia betic ket oaci d osis  
A b d o mi nal pai n or bl oati n g 
Pa ncreatitis  
 
Pre g na nc y: T here is i ns ufficie nt e vi de nce t o pr o ve safet y  of ca m ostat mesilate i n pre g na nt 
fe males.   
 
8. 1. 5  Arte misi a a n n u a te a a n d c offee  
 
Pr oc ure me nt  
 
O ut p atie nts:  C offee a n d tea b ota nical pr o d ucts will be directl y s hi p pe d o ver ni g ht t o st u d y 
patie nts, w h o are o ut patie nts b y Baes ma n o n be half of Arte mi Life .  Patie nts wit h o ut a p o d c offee 
ma ker will als o recei ve a c offee  ma ker.  
 
T he distri b ut or  f or Arte misia  a n n ua is as f oll o ws: 
Baes ma n  Distri b ut ors  
4 4 7 7 Re y n ol ds dri ve 
Hilliar d , O hi o 4 3 0 2 6 
C o ntact: T baes ma n @ baes ma n.c o m   
S u bjects ra n d o mize d t o Ar m E will ha ve t heir i nf or mati o n e ntere d i nt o t he or deri n g p ortal of 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 7 
 
Baes ma n Distri b ut ors  we bsite.   
 
 
I n p atie nts: T his b ota nical pr o d uct will be dis pe nse d b y Arte milife  t o t he I D S p har mac y. 
 
F or m ul ati o n  
Decaf c offee: 4 5 0 m g per p o d 
Tea: 2 2 5 m g per ba d 
 
Pre p ar ati o n, St or a ge a n d St a bility  
Tea a n d c offee  s h o ul d be st ore d at r o o m te m perat ure.   
 
C offee: Dis pe nse 4 2, 4 5 0  m g p o ds 
Tea: Dis pe nse 8 4, 2 2 5 m g ba gs 
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n f or s pecific a d mi nistrati o n i nstr ucti o ns  
Patie n ts s h o ul d be i nstr ucte d t o bre w 1 ( 4 5 0 m g) c offee p o d or 2 ( 2 2 5 m g) tea ba gs i n 8 oz of 
water t hree ti mes per da y Da ys 1 - 1 4. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: N o k n o w n dr u g i nteracti o ns 
  
Decrease d Effect: C Y P 2 A 6 str o n g i n d ucers ma y re d uce t he effects of Arte misia  a n n ua 
  
Her b/ N utr ace utic al I nter acti o ns:  N o k n o w n i nteracti o ns 
  
P h ar m ac oki netics  
A bs or pti o n: well a bs or be d orall y 
Distri b uti o n: N ot esta blis he d  
Meta b olis m: Meta b olize d b y C Y P 2 A 6 
Hal f-life eli mi nati o n: 1 hr 
Ter mi nal: N ot re p orte d  
E xcreti o n: N ot k n o w n 
  
A dverse Eve nts  
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %:  
N o ne re p orte d 
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
Na usea  
 
Pre g na nc y: Arte misia a n n ua  tea is use d f or t he treat me nt of malaria i n pre g na nt w o me n a n d is 
c o nsi dere d safe  
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 8 
 
8. 1. 6  Artes u n ate ( Ar m F) 
 
Pr oc ure me nt  
 
T his me dicati o n will be dis pe nse d b y I D S ser vice.  
 
F or m ul ati o n  
 
1 0 0 m g ta blet 
 
Pre p ar ati o n, St or a ge a n d St a bility  
Artes u nate  s h o ul d be st ore d at r o o m te m perat ure.   
 
Dis pe nse 2 8, 1 0 0 m g ta blets  
 
A d mi nistr ati o n  
Refer t o t he treat me nt secti o n  f or s pecific a d mi nistrati o n i nstr ucti o ns 
Patie n ts s h o ul d be i nstr ucte d t o ta ke 2 ta blets o nce a da y Da ys 1- 1 4. 
 
Dr u g I nter acti o ns  
I ncrease d Effect/ T o xicit y: N o k n o w n dr u g i nteracti o ns 
 
Decrease d Effect: C Y P 2 A 6 str o n g i n d ucers ma y re d uce t he effects of Aa  a n d artes u nate 
 
Her b/ N utr ace utic al I nter acti o ns:  N o k n o w n dr u g i nteracti o ns 
 
P h ar m ac oki netics  
A bs or pti o n: well a bs or be d orall y 
Distri b uti o n: N ot esta blis he d  
Meta b olis m: Meta b olize d b y C Y P 2 A 6  
Half -life eli mi nati o n: 1 hr 
Ter mi nal: N ot re p orte d  
E xcreti o n: N ot k n o w n 
 
A dverse Eve nts  
C o m m o n k n o w n p ote nti al t o xicities, > 1 0 %:  
Ne utr o pe nia  
A ne mia  
Na usea  
 
Less c o m m o n k n o w n p ote nti al t o xicities, 1 % - 1 0 %:  
Diarr hea  
 
Pre g na nc y: Artes u nate is use d f or t he treat me nt of malaria i n pre g na nt w o me n a n d is c o nsi dere d 
safe 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
2 9 
 
8. 1. 7  Usef ul Li n ks a n d C o ntacts 
•  
I D S we bsite :  htt ps://i dsc.s hare p oi ntsite. net . 
•  I D S e mail: I D S @ u k y.e d u 
•  I D S p h o ne a n d h o urs of ser vice: ( 8 5 9) 2 1 8- 5 5 6 2   
•  I D S Fa x: ( 8 5 9) 3 2 3- 4 7 6 5  
•  I D S h o urs M o n da y t hr o u g h Fri da y bet wee n 8: 3 0 a m a n d 4: 3 0 p m ( E T) 
 
 
9.  S T A TI S TI C A L C O N SI D E R A TI O N S  
 
9. 1  
St u d y Desi g n/ E n d p oi nts  
 
T his st u d y is a ra n d o mize d, m ulti- ar m phase II trial.  N o pr o ve n effecti ve t hera pies c urre ntl y 
e xist f or C O VI D 1 9 ( Sa n ders J et al. J A M A A pril 1 3, 2 0 2 0), t h us a selecti o n desi g n usi n g t he 
fre q ue ntist pic k-t he-wi n ner  desi g n will be e m pl o ye d as earl y scree ni n g f or pr o misi n g t hera pies. 
T he pri mar y o bjecti ve is t o ra pi dl y e val uate m ulti ple p ote ntial i n hi bit ors of S A R S-C o V -2 viral 
re plicati o n i n C O VI D 1 9 p ositi ve patie nts wit h hi g h-ris k fact ors i n or der t o decrease cli nical 
deteri orati o n, defi ne d as a less t ha n 2 p oi nt de crease i n i nitial C O VI D 7 -P OI N T O R DI N A L 
O U T C O M E S S C A L E wit hi n 1 4 da ys fr o m st u d y e ntr y ( pri mar y).  As a n e xa m ple, if a pers o n 
e nters t he st u d y at O R DI N A L S C A L E 6 a n d d oes n ot w orse n t o 4 or less, t hat is c o nsi dere d a 
s uccess. 
 
F or eac h ar m a  p hase I lea d i n p orti o n, si x patie nts per gr o u p will be f oll o we d i n or der t o 
e val uate d ose li miti n g t o xicities a n d preli mi nar y safet y.  If 2 of t he first 5 patie nts or if ≥2 of 6 
patie nts e x perie nce D L T, t he re gi me n will n ot be c o nsi dere d safe f or f urt her e val uati o n.  
 
T he trial will be p o were d base d o n t he pri mar y e n d p oi nt of t he rate of patie nts w h o will e x hi bit 
less t ha n 2 le vels of decrease i n C O VI D 7 -P OI N T O R DI N A L S C A L E fr o m baseli ne t o Da y 1 4 . 
T he g oal of selecti o n desi g ns is t o select wit h hi g h pr o ba bilit y s h o ul d a s u peri or treat me nt e xist. 
N ote t hat h y p ot hesis testi n g or c o m paris o ns bet wee n ar ms or wit h a place b o  is n ot perf or me d 
wit h t his desi g n a n d s u bse q ue nt trials are nee de d f or defi niti ve h y p ot hesis testi n g of t he 
pr o misi n g ar m.  
 
9. 2  
Sec o n d ar y E n d p oi nts  
 
Sec o n dar y e n d p oi nts relate d t o efficac y: 
•  Prese nce of  s y m pt o ms or p h ysical e xa mi nati o n si g ns relate d t o C O VI D -1 9 disease o n Da y 
1 4 i ncl u di n g: fe ver, s h ort ness of breat h, m uscle ac hes, s ore t hr oat, l oss of se nse of taste or 
s mell, etc. 
•  Prese nce  of  S A R S -C o V - 2 R N A  as  d etecte d  b y  p ol y merase  c hai n  reacti o n  ( P C R)  i n  
nas o p har y n geal sa m ples meas ure d mi ni mall y o n Da ys 1, 1 4 a n d 2 8 
•  Pr o p orti o n of patie nts wit h s y m pt o ms or p h ysical e xa mi nati o n si g ns relate d t o C O VI D- 1 9 
disease i ncl u di n g s h ort ness of breat h, m uscle ac hes, s ore t hr oat, l oss of se nse of taste or 
s mell, h os pital a d missi o n, le n gt h of sta y, s u p ple me ntal o x y ge n re q uire me nts, nee d f or 
mec ha nical ve ntilati o n,  i nte nsi ve care u nit a d missi o n, etc. 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 0 
 
•  Ti me t o i m pr o ve me nt a n d res ol uti o n of s y m pt o ms fr o m baseli ne t o Da y 1 4 a n d 2 8 
•  O x y ge n- free da ys t o Da y 2 8 
•  Ve ntilat or -free da ys t o Da y 2 8 
•  Vas o press or -free da ys t o Da y 2 8 
•  I C U-free da ys t o Da y 2 8 
•  H os pital-free da ys t o Da y 2 8 
 
Sec o n dar y e n d p oi nts relate d t o safet y a n d t olera bilit y u p t o Da y 2 8 
•  I nci de nce, se verit y, dr u g-relate d ness, a n d seri o us ness of a d verse e ve nts 
•  Pr o p orti o n of patie nts meeti n g H y’ s la w criteria 
•  Pr o p orti o n of patie nts wit h t he f oll o wi n g Li ver f u ncti o n tests ( L F T) c ha n ges:  
o  A n y A L T or A S T ≥ 5 x U L N  
o  A n y A S T or A L T ≥ 3 x U L N t o get her wit h t he a p peara nce of fati g ue, na usea, 
v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, fe ver, ras h a n d/ or e osi n o p hilia 
(e osi n o p hil perce nt or c o u nt a b o ve t he U L N) 
o  Persiste nt A L T ≥ 3 x U L N f or a peri o d of m ore t ha n 4 wee ks.  
•  Pr o p orti o n of patie nts wit h si g nifica nt c ha n ges i n E C G fi n di n gs, i ncl u di n g heart rate, E C G 
i nter vals ( P R, Q Tc B, Q Tc F), c o n d ucti o n c ha n ges, or a b n or malities i ncl u di n g se vere Q Tc 
pr ol o n gati o n of > 5 0 0 ms. 
•  Pr o p orti o n of patie nts wit h seri o us aller gic a n d s ki n reacti o ns 
•  Pr o p orti o n of patie nts wit h se vere h y p o gl yce mia 
•  Pr o p orti o n of patie nts wit h reti n o pat h y or mac ular de ge nerati o n 
•  Pr o p orti o n of patie nts wit h seiz ure 
•  Pr o p orti o n of patie nts wit h ac ute pa ncreatitis  
•  Pr o p orti o n of patie nts wit h ac ute ki d ne y i nj ur y 
•  Pr o p orti o n of patie nts wit h recei pt of re nal re place me nt t hera p y 
•  Pr o p orti o n of patie nts wit h ne utr o pe nia, l y m p h o pe nia, a ne mia, or t hr o m b oc yt o pe nia 
•  All -ca use m ortalit y rate  
 
9. 3  
S a m ple Size/ Accr u al R ate  
 
T he ass u m pti o n is t hat tra nsiti o n rate f or deteri orati o n i n cli nical scale is e q ual t o 2 0 % f or t he 
hi g h- ris k patie nts t o be e nr olle d i n t his trial base d o n a rece nt M M W R re p ort fr o m t he C D C. T he 
g oal is t o deter mi ne if a n y of t he ca n di date treat me nts will e x hi bit a 5 0 % re d ucti o n i n 
deteri orati o n of cli nical stat us (i.e. deteri orati o n rate = 1 0 %).  T h us, baseli ne sta bilit y  in cli nical 
scale ( decrease less t ha n 2 p oi nts i n C O VI D 7-P OI N T O R DI N A L S C A L E) is ass u me d t o be 
8 0 % a n d a n i m pr o ve me nt t o 9 0 % of all patie nts re mai ni n g sta ble ( decrease less t ha n 2 p oi nts i n 
C O VI D 7 -P OI N T O R DI N A L S C A L E) is h y p ot hesize d. A sa m ple of 6 0 patients i n eac h ar m is 
pr o p ose d.  If t here is a clear s u peri or treat me nt as s h o w n i n sce nari os A a n d B bel o w, t here is at 
least a n 8 2 % selecti o n pr o ba bilit y.  If t he cli nical res p o nse rate acr oss ar ms are n ot ver y 
differe nt, t he pr o ba bilit y of selecti n g t he s uperi or treat me nt is at 7 0 % a n d is m uc h hi g her 
c o m pare d t o t he ot her treat me nts (sce nari o C); w hile t here is a n e q ual c ha nce of selecti n g ar ms 
t hat ha ve si milar s u peri or efficac y (sce nari o D).   
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 1 
 
 
 
I nteri m m o nit ori n g t o assess f utilit y or efficac y will be perf or me d d uri n g t he trial usi n g t he 
Ba yesia n p osteri or pr o ba bilit y ( See Secti o n 9. 6 ).   If a t otal of 6 0 patie nts is e nr olle d i n a n ar m, 
t he pr o p ose d sa m ple size will pr o vi de a n esti mate of cli nical s uccess rate wit h wi dt h of a t w o-
si de d 9 0 % c o nfi de nce i nter val ( CI) e q ual t o 0. 1 4 3 ass u mi n g a res p o nse rate = 0. 9 0; s pecificall y, 
a 9 0 % t w o-si de d e xact bi n o mial CI = 0. 8 1 – 0. 9 5.    
 
Base d o n t his c urre nt desi g n, we pla n t o e nr oll a ma xi m u m of 2 4 0 t otal patie nts .   
 
9. 4  
R a n d o mi z ati o n/ Str atific ati o n F act ors  
 
Bl oc ke d ra n d o mizati o n wit h e q ual all ocati o n will be utilize d wit h a dj ust me nt i n ra n d o mizati o n 
se q ue nce t o acc o u nt f or t he p ote ntial t o dr o p a n ar m. Bl oc k size is 2 ti mes t he n u m ber of 
treat me nt ar ms. Ra n d o mizati o n will be stratifie d b y o ut patie nt or i n patie nt sta t us at ti me of 
e nr oll me nt i nt o t he trial.  
 
Ra n d o mizati o n list s will be ge nerate d pri or t o st u d y e nr oll me nt a n d pr o vi de d t o t he I D S 
p har macist w h o will be i n c har ge of t he ra n d o mizati o n wit h t he ra n d o mizati o n c o or di nat or.  All 
ot her st u d y pers o n nel i ncl u di n g t he PIs will be bli n de d t o t he ra n d o mizati o n lists t o pre ve nt 
patie nt a n d i n vesti gat or bias . Patie nts w h o are eli gi ble f or ra n d o mizati o n will be assi g ne d t o a 
treat me nt ar m acc or di n g t o t he ra n d o mizati o n list.  
 
I n t he sce nari o w here a treat me nt ar m is ter mi nate d earl y or a ne w treat me nt is a d de d i nt o t he 
st u d y, a ne w ra n d o mizati o n list ma y be ge nerate d t o re place t he e xisti n g o ne. T he ra n d o mizati o n 
list will gi ve e ver y patie nt e q ual pr o ba bilit y t o eac h st u d y ar m t hat is c urre ntl y a vaila ble. 
 
T he ra n d o mizati o n list will be i nc or p orate d i nt o t he O n C ore Cli nical Trials Ma na g e me nt S yste m 
a n d accessi ble  t o t he I D S p har macist. T his is facilitate d b y t he O n C ore C T M S w hic h assi g ns 
differe nt access a n d restricti o n le vels de pe n di n g o n pers o n nel r ole i n t he st u d y. Treat me nt 
all ocati o n f or eac h patie nt is t h us perf or me d b y t he I D S p har macist after St u d y C o or di nat or 
c o nfir ms patie nt eli gi bilit y stat us.  
   


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 2 
 
9. 5  
St atistic al A n al ysis Pl a n  
 
T he pri mar y a nal ysis will i ncl u de esti mate of t he rate of sta bilit y i n cli nical  scale (less t ha n 2 
p oi nt decrease i n C O VI D 7- P OI N T O R DI N A L S C A L E)  f or eac h ar m al o n g wit h e xact bi n o mial 
9 0 % c o nfi de nce i nter val.  T his is base d o n t he first res p o nse i n cli nical scale after e nr oll me nt a n d 
ra n d o mizati o n i nt o t he trial. I n a d diti o n, t he Ba yesia n p osteri or pr o ba bilit y of t he res p o nse rate 
bei n g greater t ha n 9 0 % will be calc ulate d f or eac h ar m at t he e n d of t he trial. T he rates of 
de vel o p me nt of se vere res pirat or y or or ga n fail ure, cleara nce of viral R N A at da y 2 8 a n d 
m ortalit y will be s u m mar ize d i n eac h ar m. C ha n ges i n S A R S -C o V - 2 R N A as detecte d b y 
p ol y merase c hai n reacti o n ( P C R)  o ver ti me will be s u m marize d i n eac h treat me nt ar m a n d 
c o m pare d usi n g paire d tests or l o n git u di nal li near m o dels.  
 
Sec o n dar y e n d p oi nts relate d t o pr o p orti o n of o utc o mes as i n dicate d i n Secti o n 9. 2 will be 
esti mate d al o n g wit h e xact c o nfi de nce i nter vals w hile descri pti ve statistics i ncl u di n g me dia n, 
ra n ge, I Q R will be calc ulate d f or t he d urati o n i n da ys of efficac y o utc o mes.  S ur vi val a nal ysis 
met h o ds will be utilize d t o esti mate ti me t o e ve nt e n d p oi nts.   T he e x pl orat or y a n d c orrelati ve 
e n d p oi nts s uc h as i nfla m mat or y mar kers a n d c yt o ki ne le vels will be s u m marize d at baseli ne a n d 
f oll o w- u p ti me p oi nts.  C ha n ges fr o m baseli ne will be c o m pare d usi n g paire d test or l o n git u di nal 
li near mi xe d m o dels.  
 
Sec o n dar y a nal yses will i ncl u de esti mates of rate a n d c o nfi de nce i nter vals of sta bilit y i n cli nical 
scale (less t ha n 2 p oi nt decrease i n C O VI D 7-P OI N T O R DI N A L S C A L E) eit her fr o m t he 
o ut patie nt or i n patie nt c o nti n u u m usi n g s u b gr o u p a nal yses or l o gistic re gressi o n wit h a varia ble 
t o acc o u nt f or res p o nse stat us a m o n g o ut patie nts f or eac h ar m.    
 
All patie nts w h o recei ve d st u d y dr u gs will be i ncl u de d i n t he safet y a nal ysis. T he ma xi m u m 
gra de of t o xicit y f or eac h cate g or y of i nterest will be re c or de d f or eac h patie nt a n d s u m mar y 
res ults will be ta b ulate d b y cate g or y a n d gra de. We will descri be all seri o us ( ≥ gra de 3) t o xicit y 
e ve nts.  Fre q ue nc y a n d i nci de nce ta bles of t o xicit y a n d A Es will be ge nerate d i n eac h treat me nt 
ar m.  Li ke wise, pr o p orti o ns of s pecific safet y e n d p oi nts i n Secti o n 9. 2 will be s u m marize d.   
 
m- I T T p o p ulati o n is defi ne d as all patie nts w h o ha ve bee n ra n d o mize d a n d recei ve d at least o ne 
d ose of t he st u d y treat me nt. T he pri mar y a nal ysis will be base d o n t he m-I T T p o p ulati o n. 
 
Ha n dli n g of missi n g data: T he pri mar y e n d p oi nt is base d o n a si m ple 7- scale assess me nt a n d is 
u nli kel y t o be missi n g. Patie nts w h o are i n t he m-I T T p o p ulati o n b ut ha ve missi n g pri mar y 
e n d p oi nts will be classifie d as n o n -res p o n ders t o t he treat me nt. 
 
9. 6  
I nteri m A n al ysis 
 
T he ti mi n g of i nteri m a nal ysis will be base d o n rate of patie nt accr ual. A n i nitial i nteri m a nal ysis 
will be perf or me d after 1 0 patie nts are ra n d o mize d i n eac h ar m.  F utili t y a n d efficac y will be 
assesse d i n eac h treat me nt ar m b y calc ulati n g Ba yesia n p osteri or pr o ba bilities.  T he beta 
distri b uti o n f or t he efficac y/s uccess rate is utilize d wit h a n o n -i nf or mati ve Jeffre y’s pri or e q ual 
t o beta ( 0. 5, 0. 5).   S pecificall y, a f uti lit y rate ≤ 8 0 % will be ass u me d a n d t he pr o ba bilit y f or 
st o p pi n g f or f utilit y will be set at 7 0 %.  A n efficac y rate ≥ 9 0% will be ass u me d a n d a 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 3 
 
pr o ba bilit y f or earl y st o p pi n g f or efficac y set at 9 0 %.  Base d o n t hese ass u m pti o ns, t he f utilit y 
st o p pi n g b o u n dar y f or t he first 1 0 patie nts i n eac h ar m is set at ≤ 7 patie nts wit h cli nical sta bilit y 
(i.e. less t ha n 2 p oi nt decrease i n C O VI D 7-P OI N T O R DI N A L S C A L E ) i n a s pecific treat me nt 
ar m.  
 
T he Ba yesia n met h o d ol o g y all o ws fle xi bilit y i n t he ti mi n g a n d c o h ort si ze i n eac h ar m i n t he 
c o n d uct of eac h i nteri m a nal ysis.  T h us, de pe n di n g o n patie nt e nr oll me nt a n d c o h ort size i n eac h 
ar m, s u bse q ue nt i nteri m a nal yses will be perf or me d (e. g. after e ver y 1 0 a d diti o nal patie nts i n 
eac h ar m)  a n d a d diti o nal st o p pi n g b o u n ds will be calc ulate d.  Re al -ti me assess me nts of p atie nt 
res p o nse will be critic al a n d will be f acilit ate d by cl ose c o or di n ati o n of cli nic al a n d rese arc h 
te a ms.  
 
T he decisi o n m a ki n g pr ocess f or t his tri al s uc h as dr o p pi n g a n ar m or ot her c h a n ges o n 
h o w t o pr ocee d wit h t he tri al will be b ase d o n cli nic al a n d s afet y c o nsi der ati o ns al o n g wit h 
ne wl y de vel o pi n g i nf or m ati o n o n C O VI D 1 9 as well as g ui d a nce b y res ults of effic ac y 
esti m ates a n d i nteri m p osteri or pr o b a bilities.  
 
1 0.  A D V E R S E E V E N T S:  LI S T A N D R E P O R TI N G R E Q UI R E M E N T S  
 
A d verse e ve nt ( A E) m o nit ori n g a n d re p orti n g is a r o uti ne part of e ver y cli nical trial. A d verse 
e ve nts m ust be e val uate d b y t he i n vesti gat or, gra de d a n d assi g ne d a n attri b uti o n of relate d ness t o 
st u d y treat me nt.  T he c haracteristics of a n o bser ve d A E will deter mi ne w het her t he e ve nt 
re q uires e x pe dite d re p orti n g t o O verall PI, t he F D A, t he U K I R B, a n d M C C D S M C via i n 
a d diti o n  t o r o uti ne re p orti n g.  
  
1 0. 1  E v al u ati o n of T o xicit y 
 
All patie nts will be e val ua ble f or t o xicit y fr o m t he ti me of t heir first treat me nt wit h t he 
i n vesti gati o nal a ge nts descri be d a b o ve. 
 
1 0. 2  A d verse E ve nt C h ar acteristics  
 
A d verse e ve nts ( A Es ) will be s u m marize d b y prese nti n g, f or eac h ar m, t he n u m ber a n d 
perce nta ge of patie nts ha vi n g a n y A E, ha vi n g a n A E i n eac h Me d D R A pri mar y s yste m or ga n 
class ( A p pe n di x G) a n d ha vi n g eac h i n di vi d ual A E ( preferre d ter m) i ncl u di n g relate d ness.  
A d diti o nall y, a s u m mar y of a d verse e ve nts b y preferre d ter m a n d se verit y will be perf or me d 
usi n g t he w orst se verit y gra de.   
 
All A Es m ust be e val uate d a n d c o m me nte d o n b y t he I n vesti gat or a n d gra de d acc or di n g t o t he 
D MI D T o xicit y Scale f or Deter mi ni n g Se verit y of A d verse E ve nts ( A p pe n di x G ). 
 
All relate d A Es, A Es wit h o utc o me deat h, A Es lea di n g t o per ma ne nt disc o nti n uati o n of 
treat me nt, S A Es a n d relate d S A Es will be s u m marize d b y perce nta ges a n d fre q ue ncies a n d liste d 
i ncl u di n g t he I n vesti gat or ter m, t he preferre d ter m, start a n d e n d date of A E, d urati o n ( da ys), 
se verit y, dr u g relati o ns hi p, acti o n ta ke n a n d o utc o me. 
 
•  Attri b uti o n  of t he A E: 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 4 
 
- 
Defi nite – T he A E is cle arly rel ate d t o t he st u d y treat me nt. 
- 
Pr o ba ble – T he A E is likely rel ate d t o t he st u d y treat me nt. 
- 
P ossi ble – T he A E m ay be rel ate d  t o t he st u d y treat me nt. 
- 
U nli kel y – T he A E is d o u btf ully rel ate d t o t he st u d y treat me nt. 
- 
U nrelate d – T he A E is cle arly N O T rel ate d t o t he st u d y treat me nt. 
 
1 0. 3  M C C E x pe dite d A d verse E ve nt Re p orti n g  G ui deli nes  
 
I n vesti gat ors will re p ort S A Es t hat are p ossi bl y, pr o ba bl y or defi nitel y relate d t o st u d y dr u g or 
pr oce d ures directl y t o t he M C C D S M C per t he M C C D S M C S O P a n d t he U ni versit y of 
Ke nt u c k y I R B re p orti n g p olic y, as s pecifie d  bel o w.  Use t he M C C pr ot oc ol n u m ber a n d t he 
pr ot oc ol- s pecific patie nt I D assi g ne d d uri n g trial re gistrati o n o n all re p orts.  
 
I n a d diti o n t o re p orti n g t o I R B, M C C D S M C a n d t he PI, f or a ge nts u n der a n I N D, 
i n vesti gat ors will re p ort all me dicati o n relate d ( p ossi bl y, pr o ba bl y or defi nitel y relate d) S A Es 
t o t he F D A per re q uire d re p orti n g pr ocesses usi n g Me d Watc h  f or m 3 5 0 0.  I n s u m mar y: 
1.  D uri n g p hase I r u n i n peri o d, re p ort gra de 1- 5 a d verse e ve nts (A Es ) t hat are dr u g-relate d 
( p ossi bl y, pr o ba bl y or defi nitel y relate d) t o PI, I R B, D S M C i n a n e x pe dite d fas hi o n.  
F oll o wi n g p hase I r u n-i n peri o d f or eac h ar m, re p ort gra de 3- 5 S A Es t hat are dr u g relate d 
t o PI, I R B, D S M C.  After t he p hase I r u n-i n peri o d, gra de 1 a n d 2 A Es relate d t o F D A 
a p pr o ve d me dicati o ns or b ota nical pr o d ucts are o nl y re p orte d if deter mi ne d b y t he 
i n vesti gat or t o be cli nicall y si g nifica nt A Es. 
2.  Re p ort a n y u ne x pecte d fatal or life -t hreate ni n g s us pecte d a d verse reacti o ns t o t he F D A 
n o later t ha n 7 cale n dar da ys af ter i nitial recei pt of t he i nf or mati o n.  S u b mit 7- da y re p orts 
electr o nicall y i n e C T D f or mat via t he F D A Electr o nic S u b missi o ns Gate wa y ( E S G).  
3.  Re p ort a n y seri o us, u ne x pecte d s us pecte d a d verse reacti o ns or a cli nicall y i m p orta nt 
i ncrease i n t he rate of a seri o us s us pecte d a d verse reacti o n t o t he F D A electr o nicall y i n 
e C T D f or mat via t he E S G  a n d t o all i n vesti gat ors n o later t ha n 1 5 cale n dar da ys after 
deter mi ni n g t hat t he i nf or mati o n q ualifies f or re p orti n g.   
 
D o n ot re p ort C O VI D -1 9 A Es or ot her A Es t o t hese  e ntities u nless t he y are rel ate d t o st u d y 
me dic ati o n or pr oce d ures  as liste d a b o ve.  
 
N ote:  A de at h o n st u d y re q uires b ot h  r o uti ne a n d e x pe dite d re p orti n g , re g ar dless of 
c a us alit y.  Attri b uti o n t o tre at me nt or ot her c a use m ust be pr o vi de d.  
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 5 
 
E x pe dite d Re p orti n g Re q uire me nts f or A d verse E ve nts t h at Occ ur o n Me dic ati o ns in 
St u d y Ar ms  u n der a n I N D/I D E wit hi n 3 0 D a ys of t he L ast A d mi nistr ati o n of t he 
I n vesti g ati o n al A ge nt/I nter ve nti o n 1, 2  
F D A R E P O R TI N G R E Q UI R E M E N T S F O R S E RI O U S A D V E R S E E V E N T S ( 2 1 C F R P art 3 1 2)  
N O T E:   I n v e sti g at or s M U S T  i m m e di at el y r e p ort A N Y S eri o u s A d v er s e E v e nt s, a s li st e d b el o w( 2 1 C F R 3 1 2. 6 4)  
A n a d v er s e e v e nt i s c o n si d er e d s eri o u s if it r e s ult s i n A N Y  of t h e f oll o wi n g o ut c o m e s:   
1)  
D e at h  
2)  
A lif e -t hr e at e ni n g a d v er s e e v e nt  
3)  
A n a d v er s e e v e nt t h at r e s ult s i n i n p ati e nt h o s pit ali z ati o n or pr ol o n g ati o n of e xi sti n g h o s pit ali z ati o n f or ≥ 2 4 
h o ur s  
4)  
A p er si st e nt or si g nifi c a nt i n c a p a cit y or s u b st a nti al di sr u pti o n of t h e a bilit y t o c o n d u ct n or m al lif e f u n cti o n s  
5)  
A c o n g e nit al a n o m al y/ bi rt h d ef e ct.  
6)  
I m p ort a nt M e di c al E v e nt s (I M E) t h at m a y n ot r e s ult i n d e at h, n or b e lif e -t hr e at e ni n g, n or r e q uir e 
h o s pit ali z ati o n m a y b e c o n si d er e d s eri o u s  w h e n, b a s e d u p o n m e di c al j u d g m e nt, t h e y m a y j e o p ar di z e t h e 
p ati e nt or s u bj e ct a n d m a y r e q uir e m e di c al or s ur gi c al i nt er v e nti o n t o pr e v e nt o n e of t h e o ut c o m e s li st e d i n 
t hi s d efi niti o n. ( F D A, 2 1 C F R 3 1 2. 3 2; I C H E 2 A a n d I C H E 6). 
 
A L L  S E RI O U S  a d v er s e e v e nt s t h at m e et t h e a b o v e crit eri a M U S T b e i m m e di at el y r e p ort e d vi a el e ctr o ni c 
s u b mi s si o n wi t hi n t h e ti m efr a m e s d et ail e d i n t h e t a bl e b el o w. 
H o s pit ali z ati o n  
Gr a d e 1 a n d Gr a d e 2 ( d efi nit e, p o s si bl y 
or pr o b a bl y r el at e d t o st u d y 
m e di c ati o n) Ti m efr a m e s  
Gr a d e 3 -5  ( d efi nit e, p o s si bl y, or 
pr o b a bl y r el at e d t o 
st u d y m e di c ati o n   
Ti m efr a m e s  
R e s ulti n g i n 
H o s pit ali z ati o n  
≥ 2 4 hr s  
1 0 C al e n d ar D a y s  
2 4 -H o ur ; 5 C al e n d ar D a y s  
N ot r e s ulti n g i n 
H o s pit ali z ati o n  
≥ 2 4 hr s  
N ot r e q uir e d  
N O T E:   Pr ot o c ol s p e cifi c e x c e pti o n s t o e x p e dit e d r e p orti n g of s eri o u s a d v er s e e v e nt s ar e f o u n d i n t h e S p e cifi c 
Pr ot o c ol E x c e pti o n s t o E x p e dit e d  R e p orti n g S e cti o n . 
E x p e dit e d A E r e p orti n g ti m eli n e s ar e d efi n e d a s:  
o  
“ 2 4-H o ur; 5 C al e n d ar D a y s” - T h e A E m u st i niti all y b e s u b mitt e d el e ctr o ni c all y wit hi n  2 4 h o ur s of l e ar ni n g 
of t h e A E, f oll o w e d b y a c o m pl et e e x p e dit e d r e p ort wit hi n 5 c al e n d ar d a y s of t h e i niti al 2 4 -h o ur r e p ort.  
o  
“ 1 0 C al e n d ar D a y s” - A c o m pl et e e x p e dit e d r e p ort o n t h e A E m u st b e s u b mitt e d el e ctr o ni c all y wit hi n 1 0 
c al e n d ar d a y s of l e ar ni n g of t h e A E.  
1 S eri o u s a d v er s e e v e nt s t h at o c c ur m or e t h a n 3 0 d a y s aft er t h e l a st a d mi ni str ati o n of i n v e sti g ati o n al 
a g e nt/i nt er v e nti o n a n d h a v e a n attri b uti o n of p o s si bl e, pr o b a bl e, or d efi nit e r e q uir e r e p orti n g a s f oll o w s:  
E x p e dit e d 2 4 -h o ur n otifi c ati o n f oll o w e d b y c o m pl et e r e p ort wit hi n 5 c al e n d ar d a y s f or:  
•  
All Gr a d e 3, 4, a n d Gr a d e 5 A E s  
E x p e dit e d 1 0 c al e n d ar d a y r e p ort s f or:  
Gr a d e 1 a n d 2 A E s r e s ulti n g i n h o s pit ali z ati o n or pr ol o n g ati o n of h o s pit ali z ati o n  
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 6 
 
1 0. 4  E xce pti o ns  t o A E re p orti n g 
 
A d verse e ve nts relate d t o S A R S -C o V -2 i nfecti o n are e xe m pt fr o m a d verse e ve nt re p orti n g u nless 
t he i n vesti gat or c o nsi ders t he e ve nt t o be p ossi bl y, pr o ba bl y, or defi nitel y relate d  t o t he st u d y 
dr u g or st u d y pr oce d ures.  E xa m ples of C O VI D- 1 9 relate d A Es i ncl u de:  
•  Deat h n ot relate d t o t he st u d y pr oce d ures  
•  Ne ur ol o gical e ve nts 
o  Seiz ure  
•  Car di o vasc ular e ve nts  
o  Atrial or ve ntric ular arr h yt h mia  
o  Car diac arrest  
•  Res pirat or y e ve nts  
o  H y p o xe mia re q uiri n g s u p ple me ntal o x y ge n 
o  Ac ute res pirat or y distress s y n dr o me  
o  Recei pt of mec ha nical ve ntilati o n  
o  Recei pt of e xtra -c or p oreal me m bra ne o x y ge nati o n 
 
1 0. 5  E x pe dite d Re p orti n g t o E xter n al A ge ncies  
 
O verall PI will c o m pl y wit h t he p olicies of all e xter nal f u n di n g a ge ncies a n d t he U K  I R B 
re gar di n g e x pe dite d re p orti n g, as per t he U K I R B’s Ma n date d Re p orti n g t o E xter nal A ge ncies 
S O P C 4. 0 1 5 0.   
 
1 0. 6  E x pe dite d Re p orti n g t o t he F o o d a n d Dr u g A d mi nistr ati o n ( F D A)  
 
O verall PI, as st u d y s p o ns or, will be res p o nsi ble f or all c o m m u nicati o ns wit h t he F D A. T he 
O verall PI will re p ort t o t he F D A, re gar dless of t he site of occ urre nce, a n y seri o us a d verse e ve nt 
t hat meets t he F D A’s criteria f or e x pe dite d re p orti n g f oll o wi n g t he re p orti n g re q uire me nts a n d 
ti meli nes set b y t he F D A usi n g t he Me d Watc h  3 5 0 0 f or m b y o ne of t he f oll o wi n g mea ns: 
•  T o fa x re p ort: 1- 8 0 0- F D A( 3 3 2)- 0 1 7 8 
•  T o re p ort o nli ne: w w w.f da. g o v/ me d watc h/re p ort. ht m   
•  T o re p ort b y e mail:  nase ya. mi n or @f da. h hs. g o v.   
 
1 0. 7  E x pe dite d Re p orti n g t o H os pit al Ris k M a n a ge me nt  
 
Partici pati n g i n ves ti gat ors will re p ort t o t he U K Office of Ris k Ma na ge me nt a n y partici pa nt 
safet y re p orts or se nti nel e ve nts t hat re q uire re p orti n g acc or di n g t o i nstit uti o nal p olic y.  
 
1 0. 8  R o uti ne A d verse E ve nt Re p orti n g  
 
All A d verse E ve nts  t hat are defi nitel y, pr o ba bl y or p ossi bl y relate d t o st u d y treat me nt m ust  be 
re p orte d i n r o uti ne st u d y data s u b missi o ns wit h t he e xce pti o n of t h ose liste d i n Secti o n 1 0. 4.  
A Es re p orte d e x pe diti o usl y t o t he O ver all PI a n d D S M C m ust als o be re p orte d i n r o uti ne 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 7 
 
st u d y d at a s u b missi o ns. 
 
Gr a de 1 a n d 2 a d verse e ve nts rel ate d t o F D A a p pr o ve d me dic ati o ns use d i n t his tri al (i.e. 
h y dr o x yc hl or o q ui ne, azit hr o m yci n, i ver mecti n, arte misi a a n n u a) are o nl y re p orte d if 
deter mi ne d b y t he i n vesti g at or t o be cli nic all y si g nific a nt A Es. 
 
1 0. 9  Pre g n a nc y  
 
Pre g na nc y is c o nsi dere d a n u na ntici pate d e ve nt a n d pre g na nc y as well as its o utc o me m ust be 
d oc u me nte d a n d re p orte d t o o verall PI a n d D S M C a n d Office of Researc h I nte grit y, as well t he 
F D A a n d s p o ns or i n acc or di n g t o re p orti n g re q uire me nts.  A n y pre g na nc y occ urri n g i n a patie nt 
or patie nt’s part ner fr o m t he ti me of c o nse nt t o 9 0 da ys after t he last d ose of st u d y dr u g m ust be 
re p orte d a n d t he n f oll o we d f or o utc o me.  Ne w b or n i nfa nts s h o ul d be f oll o we d u ntil 3 0 da ys ol d.   
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 8 
 
1 1.  S T U D Y C A L E N D A R  
 
 
Pre- 
St u d y  
Da y  1 
Da y 3 
or 4 
Da y 7  
+/ -2 
Da ys  
Da y 
1 0  or 
1 1  
Da y 1 4 
+/ - 4 
Da ys  
Da y 2 8  
+/ - 4 
Da ys  
Da y 4 0 * * *  
+/ - 4 Da ys  
I nvesti g ati o n al A ge nt (s) (secti o n 6. 0) 
 
A 
 
 
I nf or me d c o nse nt scree ni n g ( o pti o nal) 
X 
 
 
 
 
 
 
 
I nf or me d c o nse nt treat me nt 
 
X 
 
 
 
 
 
 
De m o gra p hics  
 
X 
 
 
 
 
 
 
Eli gi bilit y re vie w via me dical rec or d  
X 
 
 
 
 
 
 
 
Me dical hist or y  via me dical rec or d 
re vie w 
 
X 
 
 
 
X 
X 
X 
I n-pers o n e val uati o n  
 
X 
 
 
 
X 
 
 
Tele healt h c o ntact  
 
 
X a 
X a 
X a 
 
 
 
C o nc urre nt me ds  
 
X --------------------------------------------------X  
 
C B C w/ diff, plts * 
 
X  
 
 
 
X * 
 
 
Ser u m c he mistr y, ( C M P) * 
 
X  
 
 
 
X *  
 
 
E K G  f or Q Tc 
 
X b 
 
 
 
X 
X * * * *  
 
A d verse E ve nts  
 
X--------------------------------------------------- X 
 
Sta n dar d of Care Nas o p har y n geal, S wa b 
a n d S A R S -C o V -2 a nti b o d y testi n g, if 
cli nicall y i n dicate d ( o pti o nal)* * * *  
 
 
 
 
 
X * *  
X * *  
X * *  
S p ut u m s a m ple or O P s w a b ( alter n ative)  
 
X 
 
 
 
X 
X 
X 
Bl o o d s a m ple f or I nfl a m m at ory 
cyt oki nes, D-Di mer, C R P, a n d 
Pr oc alcit o ni n a n d ser oc o nversi o n ( 1 0 
m L a n d 6 m L p ur ple t o ps)  
 
X 
 
 
 
X 
X 
X 
Bl o o d s a m ple f or pl atelet st u dies ( 5 m L 
yell o w t o p) ( o pti o n al)  
 
X * *  
 
 
 
X * *  
X * *  
X * *  
C P T t u be ( 8 m L s peckle d t o p)( o pti o n al)  
 
X * *  
 
 
 
X * *  
X * *  
X * *  
S aliv a s a m ple ( o pti o n al)  
 
X * *  
 
 
 
X * *  
X * *  
X * *  
A - base d o n assi g ne d ar m  
* if n ot o btai ne d f or r o uti ne care (f or scree ni n g p hase, if n ot o btai ne d wit hi n t he pre vi o us 3 0 
da ys ; f or treat me nt p hase, if n ot o btai ne d f or r o uti ne care of C O VI D 1 9) 
* * o pti o nal  
* * * Da y 4 0 o nl y occ urs if patie nt’s ser ol o g y is ne gati ve a n d viral R N A is p osit i ve 
* * * * O nl y if i n dicate d f or r o uti ne care   
a p h o ne or tele healt h c o ntact if t he patie nt is a n o ut patie nt  
b E K G m ust b e o btai ne d wit hi n 5 da ys of re gistrati o n  
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
3 9 
 
1 2.  M E A S U R E M E N T O F E F F E C T 
 
1 2. 1  E v al u ati o n of Res p o nse 
 
S u bjects will be assesse d f or i nci de nce of c ha n ge i n C O VI D 7 -P OI N T O R DI N A L O U T C O M E S 
S C A L E fr o m t he ti me of dia g n osis t o Da y 1 4 ( pri mar y e n d p oi nt) a n d Da y 2 8 (sec o n dar y 
e n d p oi nt).  S u bject s p ut u m sa m ples will be assesse d f or viral R N A b y P C R o n Da y 1, 1 4, 2 8 
(a n d w here i n dicate d at Da y 4 0) i n t he K olesar la b.  Viral l oa ds will be e x presse d i n c o pies per 
m L a n d t he decli ne i n viral c o p y n u m ber will be assesse d bet wee n Da y 1, 1 4, 2 8 (a n d w here 
i n dicate d at Da y 4 0) usi n g S A S.   
 
1 2. 2  Ot her Res p o nse P ar a meters  
 
Partici pa nts’ me dical rec or ds will be use d t o assess t he de vel o p me nt of se vere res pirat or y or 
ot her or ga n fail ure i n t he st u d y p o p ulati o n at 4 0 da ys, as well as t o assess m ortalit y a n d rate of 
se vere a d verse e ve nts defi ne d as gra de 3 n o n he mat ol o gic or greater b y D MI D T o xicit y Scale f or 
Deter mi ni n g Se verit y of A d verse E ve nts.   
 
Safet y, t olera bilit y a n d c o m plia nce wit h of eac h re gi me n will be rec or de d o n case re p ort f or ms.  
 
 
1 3.  S T U D Y A P P R O V A L, O V E R SI G H T  A N D  D A T A R E P O R TI N G / R E G U L A T O R Y 
R E Q UI R E M E N T S  
 
1 3. 1  Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee a n d I nstit uti o n al  Re vie w B o ar d Re vie w 
 
Bef ore i m pl e me nti n g t his st u d y, t he pr ot oc ol m ust be re vie we d b y t he Mar ke y Ca ncer Ce nter’s 
Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee a n d t he pr ot oc ol, t he pr o p ose d i nf or me d c o nse nt 
f or m a n d ot her i nf or mati o n t o s u bjects, m ust be re vie we d b y t he U ni versit y of Ke nt uc k y 
I nstit uti o nal Re vie w B oar d (I R B). A si g ne d a n d date d U K I R B i nitial re vie w a p pr o val me m o 
m ust be mai ntai ne d i n t he Mar ke y Ca ncer Ce nter Cli nical Researc h Office ( M C C C R O) 
re g ulat or y bi n der. A n y a me n d me nts t o t he pr ot oc ol, ot her t ha n a d mi nistrati ve o nes, m ust be 
re vie we d a n d a p pr o ve d b y t he P R M C, st u d y s p o ns or a n d t he U K I R B.   
 
1 3. 2  Q u alit y Ass ur a nce   
 
T he M C C places t he hi g hest pri orit y o n e ns uri n g t he safet y of s u bjects partici pati n g i n cli nical 
trials a n d o n t he q ualit y of data o btai ne d fr o m cli nical a n d tra nslati o n researc h.  T he M C C 
Q ualit y Ass ura nce ( Q A) Office o versees t he mai nte na nce of q ualit y sta n dar ds i n cli nical ca ncer 
researc h t hr o u g h cli nical data m o nit ori n g of I n vesti gat or-I nitiate d Trials (II Ts) a n d r o uti ne 
a u dits. 
 
1 3. 2. 1  Data M o nit ori n g  
 
T he M C C Q A Office will c olla b orate wit h t he PI, Bi ostatisticia ns a n d Data Ma na ge me nt S pecialist 
i n creati n g a Cli nical Data M o nit ori n g Pla n ( C D M P) usi n g a ris k -base d a p pr oac h . T he C D M P will 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 0 
 
descri be t he sc o pe, c o m m u nicati o n pla n, a n d fre q ue nc y of m o nit ori n g visits. I n a d diti o n, descri be 
q uer y s u b missi o ns a n d res ol uti o ns, acti o n ite ms a n d m o nit ori n g re p orts.  
 
T he Q A m o nit or assi g ne d t o t he trial will perf or m t he m o nit ori n g tasks i n acc or da nce wit h t he 
pr ot oc ol- s pecific C D M P. T h e m o nit ori n g pr ocess will pr o vi de researc h staff a n d t he PI wit h t he 
o p p ort u nit y t o e val uate t he pr o gress of t he st u d y, verif y t he acc urac y a n d c o m plete ness of t he 
case re p ort f or ms, ass ure t hat all pr ot o c ol re q uire me nts, i ncl u di n g a p plica ble re g ulati o ns a n d 
i n vesti gat or’s o bli gati o ns are bei n g f ulfille d, a n d pr o m pt res ol uti o n of a n y i nc o nsiste ncies i n t he 
st u d y rec or ds. 
 
1 3. 2. 2  A u dit 
 
T o e ns ure c o m plia nce wit h t he I nter nati o nal C o nfere nce o n Har m o nisati o n of G o o d Cli nical 
Practice  G ui deli nes a n d all a p plica ble re g ulat or y re q uire me nts, t he M C C A u dit C o m mittee will 
c o n d uct a q ualit y ass ura nce a u dit. A mi ni m u m of  1 0 % of patie nts e nr olle d i n t he st u d y ma y be 
selecte d f or re vie w. T he p ur p ose of a M C C a u dit is t o s yste maticall y a n d i n de pe n de ntl y e xa mi ne 
all st u d y-relate d acti vities a n d d oc u me nts t o deter mi ne w het her t hese acti vities were c o n d ucte d, 
a n d data were rec or de d,  a nal yze d, a n d acc uratel y re p orte d acc or di n g t o t he pr ot oc ol, G o o d Cli nical 
Practice  g ui deli nes  of  t he  I nter nati o nal  C o nfere nce  o n  Har m o nizati o n,  a n d  a n y  a p plica ble  
re g ulat or y re q uire me nts.  
 
1 3. 3  D at a a n d S afet y M o nit ori n g C o m mittee 
 
T he M C C Data a n d Safet y M o nit ori n g C o m mittee ( D S M C) will o versee t he c o n d uct of t his trial. 
T he M C C D S M C perf or ms r o uti ne real -ti me data m o nit ori n g a n d safet y re vie w of all trials, wit h 
a s pecial f oc us u p o n i n vesti gat or -i nitiate d trials (II Ts). T he M C C D S M C will c o n d uct re vie w of 
the  trial  o n  a  sc he d ule  deter mi ne d  b y t he  M C C  Pr ot oc ol  Re vie w  &  M o nit ori n g  C o m mittee  
( P R M C).  
 
T he M C C D S M C will m o nit or t he f oll o wi n g ele me nts of t he trial: a d verse e ve nt a nal ysis, seri o us 
a d verse  e ve nts,  pr ot oc ol  de viati o ns/ vi olati o ns,  a n d  accr ual.  I n  a d diti o n,  w he n  a p plica ble  t he 
D S M C  will re vie w Q A a u dits a n d m o nit ori n g re p orts, pre vi o us re vie ws b y t he D S M C, s u g geste d 
acti o ns b y ot her c o m mittees   (s uc h as t he I R B, U K Ris k Ma na ge me nt C o m mittee), a n d ot her 
para meters a n d o utc o mes as deter mi ne d b y t he D S M C. If a p pr o priate, t he D S M C will desi g nate 
a n d m o nit or c orrecti ve acti o n(s) base d o n re vie w o utc o me. T he M C C D S M C has t he a ut h orit y t o 
a me n d, te m p oraril y s us pe n d, or ter mi nate t he trial base d u p o n patie nt safet y or c o m plia nce matters.  
A d verse e ve nt lists, g ui deli nes, a n d i nstr ucti o ns f or A E re p orti n g ca n be f o u n d i n Secti o n 1 0. 0 
( A d verse E ve nts: List a n d Re p orti n g Re q uire me nts). 
 
1 3. 4  D at a Re p orti n g 
 
1 3. 4. 1  Met h o d 
 
T his st u d y will re q uire mi ni mal data  set s u b missi o n a n d re p orti n g via t he O n C ore E nter prise 
Researc h Cli nical Trials Ma na ge me nt S yste m. Case re p ort f or ms will be create d i n a Re d Ca p 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 1 
 
data base.   I nstr ucti o ns f or s u b mitti n g data is liste d i n st u d y-s pecific g ui da nce d oc u me nts. T hese 
g ui da nce d oc u me nts ma y i ncl u de a n y of t he f oll o wi n g, as a p pr o priate f or t he sc o pe of t he st u d y: 
e C R F C o m pleti o n G ui deli nes, Data Ma na ge me nt S pecificati o ns, S u bject C o ns ole G ui de, a n d 
Q uer y Res ol uti o n G ui de.  
 
1 3. 4. 2  Res p o nsi bilit y f or Data S u b missi o n 
 
T his trial will be m o nit ore d b y t he M C C Data a n d Safet y M o nit ori n g C o m mittee ( D S M C) o n a  
sc he d ule deter mi ne d b y t he Pr ot oc ol Re vie w a n d M o nit ori n g C o m mittee at t he i nitial P R M C 
re vie w.  St u d y staff are res p o nsi ble f or s u b mitti n g st u d y data a n d/ or data f or ms as per t he Mar ke y 
Ca ncer  Ce nter  S O Ps.   St u d y  staff  are  res p o nsi ble  f or  c o m pili n g  a n d  s u b mitti n g  data  f or  all 
partici pa nts a n d f or pr o vi di n g t he data t o t he Pri nci pal I n vesti gat or f or re vie w.   
 
1 3. 5  D at a M a n a ge me nt  
 
Data ma na ge me nt will be perf or me d b y cr oss -tea m me m bers at M C C.  T hese tea m me m bers will 
i ncl u de re prese ntati ves fr o m t he Bi ostatistics a n d Bi oi nf or matics S R F, a n d t he Q ualit y Ass ura nce 
Office.  T he y will w or k cl osel y wit h st u d y staff t o e ns ure ti mel y a n d acc urate data s u b missi o n.  A 
pr ot oc ol- s pecific  Data  Ma na ge me nt  Pla n  ( D M P)  will  be  a ut h ore d  b y  t he  bi ostatisticia n  a n d  
Pri n ci pal I n vesti gat or wit h eac h e x pecte d t o re vie w a n d a p pr o ve t he fi nalizati o n of t he D M P.  I n 
or der t o mai ntai n best cli nical practices i n data ma na ge me nt, t he D M P ma y i ncl u de, b ut n ot be 
li mite d t o: C R F/e C R F desi g n, data base b uil d a n d desi g n, data base trai ni n g, e dit c hec k/ vali dati o n 
s pecificati o ns,  st u d y  data base  testi n g/release,  data  a n d  pa per  w or kfl o w,  re p ort,  metrics,  
q uer y/ discre pa nc y ma na ge me nt, ma na ge me nt of e xter nal (i ncl u di n g la b) data, me dical c o di n g, 
S A E ha n dli n g/rec o nciliati o n, data tra nsfers a n d  data base l oc k. T he pr ot oc ol -s pecific D M P will 
a d diti o nall y defi ne t he sc he d ule at w hic h data will be accesse d b y data ma na ge me nt a n d st u d y 
statisticia n t o perf or m statistical pr o gra m mi n g f or c o n d uct of data q ualit y, data c o ntr ol, data 
ma na ge me nt, ge nerati o n of i nteri m re p orts a n d statistical a nal ysis. Cr oss -tea m me m bers will 
c olla b orate t o esta blis h pr oce d ures a n d ti meli nes f or q ualit y c o ntr ol, a u dits, q uer y res ol uti o n, 
a n n ual re p orts, i nteri m a nal ysis a n d fi nal data a nal ysis.  
 
1 3. 6  C o m pli a nce wit h L a ws a n d Re g ul ati o ns 
 
T he st u d y will be c o n d ucte d i n acc or da nce wit h U. S. F o o d a n d Dr u g A d mi nistrati o n ( F D A) a n d 
I nter nati o nal C o nfere nce o n Har m o ni zati o n (I C H) G ui deli nes f or G o o d Cli nical Practice ( G C P), 
t he Declarati o n of Helsi n ki, a n y a p plica ble l ocal healt h a ut h orit y, a n d I nstit uti o nal Re vie w B oar d 
(I R B) re q uire me nts.  T he PI or desi g nee will be res p o nsi ble f or o btai ni n g c o nti n ui n g a n d n ot less 
t ha n a n n ual I R B re-a p pr o val t hr o u g h o ut t he d urati o n of t he st u d y.  C o pies of t he I n vesti gat or’s 
a n n ual re p ort t o t he I R B a n d c o pies of t he I R B c o nti n ua nce of a p pr o val m ust mai ntai ne d b y t he 
M C C C R O.  T he PI or desi g nee is als o res p o nsi ble f or n otif yi n g t he Data a n d Safet y M o nit ori n g 
C o m mittee of t he M C C a n d t he U K I R B of a n y si g nifica nt a d verse e ve nts t hat are seri o us a n d/ or 
u ne x pecte d, as per S O P’s of t h ose e ntities  a n d c o m plia nce wit h pr ot oc ol re q uire me nts. D S M C 
will re vie w all a d verse e ve nts of t his II T as per its S O P.  
 
1 4.  R E F E R E N C E S  
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 2 
 
1.  
d el Ri o C, M al a ni P N. C O VI D -1 9 — N e w I nsi g hts o n a R a pi dl y C h a n gi n g E pi d e mic. 
J A M A 2 0 2 0.  
2.  
H u a n g C, W a n g Y, Li X et al. Cli nic al f e at ur es of p ati e nts i nf ect e d wit h 2 0 1 9 n o v el 
c or o n a vir us i n W u h a n, C hi n a. L a nc et 2 0 2 0; 3 9 5: 4 9 7 -5 0 6.  
3.  
S o hr a bi C, Als afi Z, O' N eill N et al. W orl d H e alt h Or g a niz ati o n d ecl ar es gl o b al 
e m er g e ncy: A r e vi e w of t h e 2 0 1 9 n o v el c or o n a vir us ( C O VI D -1 9). I nt J S ur g 2 0 2 0; 7 6: 7 1 -7 6.  
4.  
W u Z, Mc G o o g a n J M. C h ar act eristics of a n d I m p ort a nt L ess o ns Fr o m t h e C or o n a vir us 
Dis e as e 2 0 1 9 ( C O VI D -1 9) O ut br e a k i n C hi n a: S u m m ar y of a R e p ort of 7 2 3 1 4 C as es Fr o m t h e 
C hi n es e C e nt er f or Dis e as e C o ntr ol a n d Pr e v e nti o n. J A M A 2 0 2 0.  
5.  
G u a n W -j, Ni Z-y, H u Y et al. Cli nic al C h ar act eristics of C or o n a vir us Dis e as e 2 0 1 9 i n 
C hi n a. N e w E n gl a n d J o ur n al of M e dici n e 2 0 2 0.  
6.  
C h e n N, Z h o u M, D o n g X et al. E pi d e mi ol o gic al a n d cli nic al c h ar act eristics o f 9 9 c as es 
of 2 0 1 9 n ov el c or o n a vir us p n e u m o ni a i n W u h a n, C hi n a: a d escri pti v e st u d y. L a nc et 2 0 2 0; 3 9 5: 
5 0 7 -5 1 3.  
7.  
W a n g D, H u B, H u C et al. Cli nic al C h ar act eristics of 1 3 8 H os pit aliz e d P ati e nts Wit h 
2 0 1 9 N o v el C or o n a vir us -I nf ect e d P n e u m o ni a i n W u h a n, C hi na. J A M A 2 0 2 0.  
8.  
X u X W, W u X X, Ji a n g X G et al. Cli nic al fi n di n gs i n a gr o u p of p ati e nts i nf ect e d wit h 
t h e 2 0 1 9 n o v el c or o n a vir us ( S A R S-C ov -2) o utsi d e of W u h a n, C hi n a: r etr os p ecti v e c as e s eri es. 
B MJ 2 0 2 0; 3 6 8: m 6 0 6.  
9.  
W u C, C h e n X, C ai Y et al. Ris k F act or s Ass oci at e d Wit h Ac ut e R es pir at or y Distr ess 
S y n dr o m e a n d D e at h i n P ati e nts Wit h C or o n a vir us Dis e as e 2 0 1 9 P n e u m o ni a i n W u h a n, C hi n a. 
J A M A I nt er n al M e dici n e 2 0 2 0. 
1 0.  
Gi ac o m elli A, P ezz ati L, C o nti F et al. S elf -r e p ort e d olf act or y a n d t ast e dis or d ers i n 
S A R S- C o V -2 p ati e nts: a cr oss -s ecti o n al st u d y. Cli n I nf ect Dis 2 0 2 0. 
1 1.  
G ar g S KL, W hit a k er M, O’ H all or a n A, C u m mi n gs C. H os pit aliz ati o n R at es a n d 
C h ar act eristics of P at e nts H os pit aliz e d wit h L a b or at or y -C o nfir m e d C or o n a vir us Dis e as e 2 0 1 9 - 
C O VI D - N E T, 1 4 St at e s, M arc h 1-3 0, 2 0 2 0. M M W R M or b M ort al W kl y R e p 2 0 2 0.  
1 2.  
B hi mr aj A M R, S h u m a k er A H, L a v er g n e V, B a d e n L, C h e n g V C C, E d w ar ds K M, G a n d hi 
R, M ull er WJ, O’ H or o J C, S h o h a m S, M ur a d M H, M ust af a R A, S ult a n S, F alc k -Ytt er Y. I nf ecti o us 
Dis e as es S oci ety of A m eric a G ui d eli n es o n t h e Tr e at m e nt a n d M a n a g e m e nt of P ati e nts wit h 
C O VI D -1 9 I nf ecti o n. I n. 2 0 2 0.  
1 3.  
C al y L, Dr uc e J D, C att o n M G et al. T h e F D A -a p pr ov e d Dr u g Iv er m ecti n i n hi bits t h e 
r e plic ati o n of S A R S-C o V -2 i n vitr o. A nti vir al R es 2 0 2 0; 1 0 4 7 8 7.  
1 4.  
C al y L, Dr uc e  J D, C att o n M G et al. T h e F D A-a p pr ov e d dr u g i v er m ecti n i n hi bits t h e 
r e plic ati o n of S A R S-C o V -2 i n vitr o. A nti vir al R es 2 0 2 0; 1 7 8: 1 0 4 7 8 7.  
1 5.  
Lifsc hitz A, Vir k el G, S all ovitz J et al. C o m p ar ati v e distri b uti o n of i v er m ecti n a n d 
d or a m ecti n t o p ar asit e l oc ati o n tiss u es i n c attl e. V et P ar asit ol 2 0 0 0; 8 7: 3 2 7 -3 3 8.  
1 6.  
Y a m a y a M, S hi m ot ai Y, H at ac hi Y et al. T h e s eri n e pr ot e as e i n hi bit or c a m ost at 
i n hi bits i nfl u e nz a vir us r e plic ati o n a n d c yt o ki n e pr o d ucti o n i n pri m ar y c ult ur es of h u m a n 
tr ac h e al e pit h eli al c ells. P ulm P h ar m ac ol T h er 2 0 1 5; 3 3: 6 6 -7 4.  
1 7.  
H off m a n n M, Kl ei n e -W e b er H, Sc hr o e d er S et al. S A R S -C o V -2 C ell E ntr y D e p e n ds o n 
A C E 2 a n d T M P R S S 2 a n d Is Bl oc k e d b y a Cli nic all y Pr ov e n Pr ot e as e I n hi bit or. C ell 2 0 2 0; 1 8 1: 2 7 1 -
2 8 0. e 2 7 8.  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 3 
 
1 8.  
K a w as e M, S hir at o K, v a n d er H o e k L et al. Si m ult a n e o us tr e at m e nt of h u m a n 
br o nc hi al e pit h eli al c ells wit h s eri n e a n d c yst ei n e pr ot e as e i n hi bit ors pr e v e nts s e v er e ac ut e 
r es pir at or y sy n dr o m e c or o n a vir us e ntr y. J Vir ol 2 0 1 2; 8 6: 6 5 3 7-6 5 4 5.  
1 9.  
Z h o u Y, V e d a nt h a m P, L u K et al. Pr ot e as e i n hi bit ors t ar g eti n g c or o n a vir us a n d 
fil ovir us e ntr y. A nti vir al R es 2 0 1 5; 1 1 6: 7 6-8 4.  
2 0.  
C o ot e K, At h ert o n -W ats o n H C, S u g ar R et al. C a m ost at att e n u at es air w a y e pit h eli al 
s o di u m c h a n n el f u ncti o n i n vi v o t hr o u g h t h e i n hi biti o n of a c h a n n el-activ ati n g pr ot e a s e. J 
P h ar m ac ol Ex p T h er 2 0 0 9; 3 2 9: 7 6 4 -7 7 4.  
2 1.  
R o w e S M, R e e v es G, H at h or n e H et al. R e d uc e d s o di u m tr a ns p ort wit h n as al 
a d mi nistr ati o n of t h e pr ost asi n i n hi bit or c a m ost at i n s u bj ects wit h c ystic fi br osis. C h est 2 0 1 3; 
1 4 4: 2 0 0 -2 0 7.  
2 2.  
S ai J K, S u y a m a M, K u b o k a w a Y et al. Effic acy of c a m ost at m esil at e a g ai nst d ys p e psi a 
ass oci at e d wit h n o n -alc o h olic mil d p a ncr e atic dis e as e. J o ur n al of G astr o e nt er ol o g y 2 0 1 0; 4 5: 
3 3 5 -3 4 1.  
2 3.  
P ar n h a m MJ, Er a k ovic H a b er V, Gi a m ar ell os -B o ur b o ulis EJ et al. Azit hr o m yci n: 
m ec h a nis ms of acti o n a n d t h eir r el e v a nc e f or cli nic al a p plic ati o ns. P h ar m ac ol T h er 2 0 1 4; 1 4 3: 
2 2 5 -2 4 5.  
2 4.  
G a o J, Ti a n Z, Y a n g X. Br e a kt hr o u g h: C hl or o q ui n e p h os p h at e h as s h o w n a p p ar e nt 
effic ac y i n tr e at m e nt of C O VI D -1 9 ass oci at e d p n e u m o ni a i n cli nic al st u d i es. Bi osci Tr e n ds 2 0 2 0; 
1 4: 7 2 -7 3.  
2 5.  
Vi nc e nt MJ, B er g er o n E, B e nj a n n et S et al. C hl or o q ui n e is a p ot e nt i n hi bit or of S A R S 
c or o n a vir us i nf ecti o n a n d s pr e a d. Vir ol J 2 0 0 5; 2: 6 9.  
2 6.  
K e y a erts E, Vij g e n L, M a es P et al. I n vitr o i n hi biti o n of s e v er e ac ut e r es pir at or y 
s y n dr o m e c or o n a vir us b y c hl or o q ui n e. Bi oc h e m Bi o p h ys R es C o m m u n 2 0 0 4; 3 2 3: 2 6 4 -2 6 8.  
2 7.  
D e v a ux C A, R ol ai n J M, C ols o n P, R a o ult D. N e w i nsi g hts o n t h e a nti vir al eff ects of 
c hl or o q ui n e a g ai nst c or o n a vir us: w h at t o ex p ect f or C O VI D -1 9 ? I nt J A nti m icr o b A g e nts 2 0 2 0; 
1 0 5 9 3 8.  
2 8.  
W a n g M, C a o R, Z h a n g L et al. R e m d esi vir a n d c hl or o q ui n e eff ecti v ely i n hi bit t h e 
r ec e ntl y e m er g e d n ov el c or o n a vir us ( 2 0 1 9-n C o V) i n vitr o. C ell R es e arc h 2 0 2 0; 3 0: 2 6 9 -2 7 1.  
2 9.  
H or b y P L M. R a n d o mis e d E v al u ati o n of C ovi d -1 9 T h er a p y: N C T 0 4 3 8 1 9 3 6: N o cli nic al 
b e n efit fr o m us e of h y dr ox yc hl or o q ui n e i n h os pit alis e d p ati e nts wit h C O VI D -1 9. I n. 2 0 2 0.  
3 0.  
R estr e p o A. U p d at e o n h y dr ox yc hl or o q ui n e, W H O. I n. 2 0 2 0.  
3 1.  
Hi nt o n D. L ett er R e v o ki n g t h e E m er g e nc y Us e A ut h oriz ati o n f or E m er g e nc y Us e of 
C hl or o q ui n e P h os p h at e a n d H y dr oxyc hl or o q ui n e S ulf at e a g ai nst C ovi d -1 9. I n S er vic es D o H a H 
( e d). F D A w e bsit e: 2 0 2 0. 
3 2.  
J u urli n k D N. S af et y c o nsi d er ati o ns wit h c hl or o q ui n e, h y dr ox yc hl or o q ui n e a n d 
azit hr o m yci n i n t h e m a n a g e m e nt of S A R S -C o V -2 i nf ecti o n.  C m aj 2 0 2 0.  
3 3.  
R et all ac k H, Di L ull o E, Ari as C et al. Zi k a vir us c ell tr o pis m i n t h e d e v el o pi n g h u m a n 
br ai n a n d i n hi biti o n b y azit hr o m yci n. Pr oc N atl Ac a d Sci U S A 2 0 1 6; 1 1 3: 1 4 4 0 8 -1 4 4 1 3.  
3 4.  
M a dri d P B, P a nc h al R G, W arr e n T K et al. E v al u ati o n of E b ol a V ir us I n hi bit ors f or Dr u g 
R e p ur p osi n g. A C S I nf ect Dis 2 0 1 5; 1: 3 1 7 -3 2 6.  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 4 
 
3 5.  
B ac h ari er L B, G uil b ert T W, M a u g er D T et al. E arl y A d mi nistr ati o n of Azit hr o m yci n 
a n d Pr e v e nti o n of S e v er e L o w er R es pir at or y Tr act Ill n ess es i n Pr esc h o ol C hil dr e n Wit h a Hist or y 
of S uc h Ill n ess es: A R a n d o miz e d Cli nic al Tri al. J A M A 2 0 1 5; 3 1 4: 2 0 3 4 -2 0 4 4.  
3 6.  
G a utr et P, L a gi er J C, P ar ol a P et al. H y dr ox yc hl or o q ui n e a n d azit hr o m yci n as a 
tr e at m e nt of C O VI D-1 9: r es ults of a n o p e n -l a b el n o n-r a n d o miz e d cli nic al tri al. I nt J A nti micr o b 
A g e nts 2 0 2 0; 1 0 5 9 4 9.  
3 7.  
M oli n a J M, D el a u g err e C, G off JL et al. M e d M al I nf ect 2 0 2 0.  
3 8.   
K o nst at-K orz e n n y E, Asc e nci o -Ar a g o n J A, Ni ez e n -L u g o S, V az q u ez-L o p ez R. 
Art e misi ni n a n d Its S y nt h etic D eri v ati v es as a P ossi bl e T h er a p y f or C a nc er. M e d Sci ( B as el) 2 0 1 8; 
6.  
3 9.  
R aff eti n A, Br u n e el F, R o uss el C et al. Us e of art es u n at e i n n o n -m al ari al i n dic ati o ns. 
M e d M al I nf ect 2 0 1 8; 4 8: 2 3 8 -2 4 9.  
4 0.  
M u n y a n gi J, C or n et -V er n et L, I d u m b o M et al. Art e misi a a n n u a a n d Art e misi a afr a 
t e a i nf usi o ns vs. art es u n at e-a m o di a q ui n e ( A S A Q) i n tr e ati n g Pl as m o di u m f alci p ar u m m al ari a i n 
a l ar g e sc al e, d o u bl e bli n d, r a n d o miz e d cli nic al tri al. P h yt o m e dici n e 2 0 1 9; 5 7: 4 9 -5 6.  
4 1.  
Gil m or e K O, K; S e e b er g er, P H. Art e misi a a n n u a Pl a nt Extr acts ar e Acti v e A g ai nst 
S A R S -C o V -2 I n Vitr o"; s u b mitt e d f or p u blic ati o n. I n. 2 0 2 0.  
4 2.  
Ar or a M, S ax e n a P, C h o u d h ar y D K et al. D u al s y m bi osis b et w e e n Pirif or m os p or a 
i n dic a a n d Az ot o b act er c hr o oc occ u m e n h a nc es t h e art e misi ni n c o nt e nt i n Art e misi a a n n u a L. 
W orl d J Micr o bi ol Bi ot ec h n ol 2 0 1 6; 3 2: 1 9.  
4 3.  
D esr osi ers M R, Mittl e m a n A, W e at h ers PJ. Dri e d L e af Art e misi a A n n u a I m pr ov es 
Bi o a v ail a bilit y of Art e misi ni n vi a C yt oc hr o m e P 4 5 0 I n hi biti o n a n d E n h a nc es Art e misi ni n Effic acy 
D o w nstr e a m. Bi o m ol ec ul es 2 0 2 0; 1 0: 2 5 4.  
4 4.  
A dj ei G O, K urtz h als J AL, R o dri g u es O P et al. A m o di a q ui n e -art es u n at e vs art e m et h er -
l u m ef a ntri n e f or u nc o m plic at e d m al ari a i n G h a n ai a n c hil dr e n: a r a n d o miz e d effic ac y a n d s af et y 
tri al wit h o n e y e ar f oll o w-u p. M al ari a j o ur n al 2 0 0 8; 7: 1 2 7 -1 2 7.  
4 5.  
G ui di M, M erci er T, A o uri M et al. P o p ul ati o n p h ar m ac o ki n etics a n d 
p h ar m ac o d y n a mics of t h e art es u n at e – m efl o q ui n e fix e d d os e c o m bi n ati o n f or t h e tr e at m e nt of 
u nc o m plic at e d f alci p ar u m m al ari a i n Afric a n c hil dr e n. M al ari a J o ur n al 2 0 1 9; 1 8: 1 3 9.  
4 6.  
N di a y e JL, R a n dri a n ari v el oj osi a M, S a g ar a I et al. R a n d o miz e d, m ultic e ntr e 
as s ess m e nt of t h e effic ac y a n d s af ety of A S A Q – a fix e d -d os e art es u n at e -a m o di a q ui n e 
c o m bi n ati o n t h er a p y i n t h e tr e at m e nt of u nc o m plic at e d Pl as m o di u m f alci p ar u m m al ari a. 
M al ari a J o ur n al 2 0 0 9; 8: 1 2 5.  
4 7.  
C e nt er f or Dis e as e C o ntr ol: I nf or m ati o n f or H e alt hc ar e Pr of essi o n als: C O VI D -1 9 a n d 
U n d erl yi n g C o n diti o ns. I n. N ati o n al C e nt er f or I m m u niz ati o n a n d R es pir at or y Dis e as es ( N CI R D), 
Di visi o n of Vir al Dis e as es.  
4 8.  
M a h aj a n R, G u pt a K. A d a pti v e d esi g n cli nic al tri als: M et h o d ol o g y, c h all e n g es a n d 
pr os p ect. I n di a n j o ur n al of p h ar m ac ol o g y 2 0 1 0; 4 2: 2 0 1 -2 0 7.  
4 9.  
B a u er P, Ki es er M. C o m bi ni n g diff er e nt p h as es i n t h e d e v el o p m e nt of m e dic al 
tr e at m e nts wit hi n a si n gl e tri al. St at M e d 1 9 9 9; 1 8: 1 8 3 3-1 8 4 8.  
5 0.  
B erry S M, Si n g h C, L a n g J D et al. Str e a mli ni n g g e n e ex pr essi o n a n al ys is: i nt e gr ati o n 
of c o -c ult ur e a n d m R N A p urific ati o n. I nt e gr Bi ol ( C a m b) 2 0 1 4; 6: 2 2 4 -2 3 1.  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 5 
 
5 1.  
B erry S M, Al ari d E T, B e e b e DJ. O n e -st e p p urific ati o n of n ucl eic aci d f or g e n e 
ex pr essi o n a n al ysis vi a I m misci bl e Filtr ati o n Assist e d b y S urf ac e T e nsi o n (I F A S T). L a b C hi p 2 0 1 1; 
1 1: 1 7 4 7 -1 7 5 3.  
5 2.  
B erry S M, P ezzi H M, Willi a ms E D et al. Usi n g Excl usi o n -B as e d S a m pl e Pr e p ar ati o n 
( E S P) t o R e d uc e Vir al L o a d Ass a y C ost. PL o S O n e 2 0 1 5; 1 0: e 0 1 4 3 6 3 1. 
5 3.  
C as a v a nt B P, G uc k e n b er g er DJ, B e e b e DJ, B err y S M. Effici e nt s a m pl e pr e p ar ati o n 
fr o m c o m pl ex bi ol o gic al s a m pl es usi n g a sli di n g li d f or i m m o biliz e d dr o pl et extr acti o ns. A n al 
C h e m 2 0 1 4; 8 6: 6 3 5 5 -6 3 6 2.  
5 4.  
S p er g er J M, Str ot m a n L N, W els h A et al. I nt e gr at e d A n al ysis of M ulti pl e Bi o m ar k ers 
fr o m Circ ul ati n g T u m or C ells E n a bl e d b y Excl usi o n -B as e d A n al yt e Is ol ati o n. Cli n C a nc er R es 
2 0 1 7; 2 3: 7 4 6 -7 5 6.  
5 5.  
Sc h e hr JL, Sc h ultz Z D, W arric k J W et al. Hi g h S p ecificity i n Circ ul ati n g T u m or C ell 
I d e ntific ati o n Is R e q uir e d f or Acc ur at e E v al u ati o n of Pr o gr a m m e d D e at h-Li g a n d 1. PL o S O n e 
2 0 1 6;  1 1: e 0 1 5 9 3 9 7.  
5 6.  
W o n g C K, L a m C W, W u A K et al. Pl as m a i nfl a m m at or y c yt oki n es a n d c h e m o ki n es i n 
s e v er e ac ut e r es pir at ory s y n dr o m e. Cli n Ex p I m m u n ol 2 0 0 4; 1 3 6: 9 5-1 0 3.  
5 7.  
M a h all a wi W H, K h a b o ur O F, Z h a n g Q et al. M E R S -C o V i nf ecti o n i n h u m a ns is 
ass oci at e d wit h a pr o -i nfl a m m at ory T h 1 a n d T h 1 7 c yt o ki n e pr ofil e. C yt o ki n e 2 0 1 8; 1 0 4: 8-1 3.  
5 8.  
G e e J R, S altzst ei n D R, Ki m K et al. A P h as e II R a n d o miz e d, D o u bl e -bli n d, Pr es ur gic al 
Tri al of P ol y p h e n o n E i n Bl a d d er C a nc er P ati e nts t o E v al u at e P h ar m ac o d y n a mics a n d Bl a d d er 
Tiss u e Bi o m ar k ers. C a nc er Pr e v R es ( P hil a) 2 0 1 7; 1 0: 2 9 8 -3 0 7.  
5 9.  
El e w a H, Wil b y KJ. A R e vi e w of P h ar m ac o g e n etics of A nti m al ari als a n d Ass oci at e d 
Cli nic al I m plic ati o ns. E ur J Dr u g M et a b P h ar m ac o ki n et 2 0 1 7; 4 2: 7 4 5 -7 5 6.  
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 6 
 
A P P E N DI X A: O B E SI T Y S C A L E 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 7 
 
A P P E N DI X B:  C O VI D 7 -P OI N T O R DI N A L O U T C O M E S S C A L E  
htt p:// w w w. w h o.i nt/ bl ue pri nt/ pri orit y -diseases/ ke y -acti o n/ n o vel-c or o na vir us/e n/ 
 
C O VI D 7 -p oi nt or di n al o utc o mes sc ale:  
1.  Deat h  
2.  H os pitalize d o n i n vasi ve mec ha nical ve ntilati o n or E C M O  
3.  H os pitalize d o n n o n-i n vasi ve ve ntilati o n or hi g h fl o w nasal ca n n ula 
4.  H os pitalize d o n s u p ple me ntal o x y ge n 
5.  H os pitalize d n ot o n s u p ple me ntal o x y ge n 
6.  N ot h os pitalize d wit h li mitati o n i n acti vit y (c o nti n ue d s y m pt o ms)  
7.  N ot h os pitalize d wit h o ut li mitati o n i n acti vit y ( n o s y m pt o ms)  
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 8 
 
A P P E N DI X C: PI L L / P R O D U C T DI A R I E S  
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
4 9 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y Dr u g Di ar y  
 
Please rec or d h o w ma n y ta blets y o u ta ke, t he ti me y o u ta ke t he m a n d a n y c o m me nts bel o w a n d 
bri n g t he c o m plete d Diar y as well as y o ur st u d y dr u g s u p pl y, i ncl u di n g e m pt y b ottles, t o e ver y 
st u d y visit. T his will hel p us kee p trac k of y o ur st u d y dr u g a n d h o w well y o u are t olerati n g it. 
Ar m C 
 
P artici p a nt I de ntifier:   
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C  
D oct or:  J a mes Z a c h ar y P orterfiel d, M D   
  
 
D oct or: S us a n ne M ar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
 
 
 
Y o u will t a ke t he f oll o wi n g n u m ber of c a ps ules/t a blets e ac h ti me ( per d ose) as liste d i n t he t a ble 
bel o w:  
 
St u d y Dr u g N a me  
# of c a ps ules (t a blets) 
t o t a ke per ti me/ d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke dr u g  
I ver mecti n 
_ _ t a blets/ 1 2 m g -1 5 m g  
                (circle o ne) 
O nce a d a y  
2 h o urs bef ore 
or 2 h o urs 
after a me al  
_ _: _ _ _ 
 a. m . 
 
 
 
D a y  
D ate  
N u m ber of I ver mecti n T a blets  
Ti me of D ose  
1  
 
_ _  
_ _ _ _: _ _ _ _  □ a. m. 
 □ D ose N ot Ta ke n  W h y: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
 
_ _  
_ _ _ _: _ _ _ _  □ a. m. 
 □ D ose N ot Ta ke n  W h y: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 0 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 1 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y Dr u g Di ar y  
 
Please rec or d h o w ma n y ta blets y o u ta ke, t he ti me y o u ta ke t he m a n d a n y c o m me nts bel o w a n d 
bri n g t he c o m plete d Diar y as well as y o ur st u d y dr u g s u p pl y, i ncl u di n g e m pt y b ottles, t o e ver y 
st u d y visit. T his will hel p us kee p trac k of y o ur st u d y dr u g a n d h o w well y o u are t olerati n g it.  
 
Ar m D  
 
Partici pa nt I de ntifier:     
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C   
D oct or:  Ja mes Zac har y P orterfiel d, M D   
 
 
D oct or: S usa n ne Mar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
  
  
  
  
 
 
 
Y o u will ta ke t he f oll o wi n g n u m ber of ca ps ules/ta blets  eac h ti me ( per d ose)  as liste d i n t he ta ble bel o w:  
 
St u d y Dr u g N a me  
# of c a ps ules 
(t a blets) t o t a ke per 
ti me/ d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke dr u g  
Ca m ostat Mesilate  
2 ta blets  
3 ti mes per 
da y  
_ _: _ _ _ 
 a. m.    
_ _: _ _ _ 
 p. m.  
_ _: _ _ _ 
 p. m.  
 
 
 
 
D a y  
D ate  
N u m ber 
of  
C a m ost at 
Mesil ate    
1 0 0 m g  
Ti me of D ose  
N u m ber 
of  
C a m ost at 
Mesil ate    
1 0 0 m g  
Ti me of D ose  
N u m ber of  
C a m ost at 
Mesil ate  
t a blets 
Ti me of D ose  
1 
 
2 
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
3 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
4 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
5 
 
2  
_ _ _: _ _ _   □ a. m. 
2  
_ _ _: _ _ _   □ p . m. 
2  
_ _ _: _ _ _   □ p . m. 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 2 
 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
6 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
8 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
9 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 0 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 1 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 2 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 3 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 4 
 
2  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 3 
 
 
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 4 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y B ot a nic al  Di ar y  
 
Please rec or d t he n u m ber of ti mes y o u dri n k t he Arte misia  a n n ua tea or c offee, t he ti me y o u ta ke 
t he m a n d a n y c o m me nts bel o w a n d bri n g t he c o m plete d Diar y as well as y o ur st u d y tea or c offee 
s u p pl y, t o y o ur ne xt st u d y visit. T his will hel p us kee p trac k of y o ur st u d y pr o d uct a n d h o w well 
y o u are t olerati n g it.   
 
Ar m E  
 
Partici pa nt I de ntifier:     
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C   
D oct or:  Ja mes Zac har y P orterfiel d, M D   
 
 
D oct or: S usa n ne Mar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
  
  
  
  
 
 
 
Y o u will ta ke t he f oll o wi n g n u m ber of ca ps ules/ta blets  eac h ti me ( per d ose)  as liste d i n t he ta ble bel o w:  
 
St u d y B ot a nic al 
Pr o d uct N a me  
d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke te a or 
c offee  
Arte misia  a n n ua   
1 p o d or 2  tea ba gs 
3 ti mes per 
da y  
_ _: _ _ _ 
 a. m.    
_ _: _ _ _ 
 p. m.  
_ _: _ _ _ 
 p. m.  
 
 
 
 
D a y  
D ate  
N u m ber of  
Arte misi a  
a n n u a  te a 
b a g or p o d  
Ti me of D ose  
N u m ber of  
Arte misi a  
a n n u a  te a 
b a g or p o d  
Ti me of D ose  
N u m ber of  
Arte misi a  
a n n u a te a 
b a g or p o d  
Ti me of D ose  
1 
 
_ 
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 5 
 
5 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
6 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
8 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
9 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 0 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 1 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 6 
 
 
 
 
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 7 
 
 
St u d y P artici p a nt Self -A d mi nistr ati o n St u d y Dr u g Di ar y  
 
Please rec or d t he n u m ber of ti mes y o u dri n k t he Artes u nate tea or c offee, t he ti me y o u ta ke t he m 
a n d a n y c o m me nts bel o w a n d bri n g t he c o m plete d Diar y as well as y o ur st u d y tea or c offee 
s u p pl y, t o y o ur ne xt st u d y visit. T his will hel p us kee p trac k of y o ur st u d y dr u g a n d h o w well 
y o u are t olerati n g it.   
 
Ar m F  
 
Partici pa nt I de ntifier:     
  
 
Pr ot oc ol #: M C C -2 0 -C O VI D -0 1 -P M C   
D oct or:  Ja mes Zac har y P orterfiel d, M D   
 
 
D oct or: S usa n ne Mar kes ber y Ar n ol d, M D  
N urse: e nter n a me a n d p h o ne n u m ber  
  
  
  
  
 
 
 
Y o u will ta ke t he f oll o wi n g n u m ber of ca ps ules/ta blets  eac h ti me ( per d ose)  as liste d i n t he ta ble bel o w:  
 
St u d y Dr u g N a me  
d ose  
# of 
ti mes/ d oses 
e ac h d a y  
A p pr o xi m ate ti me t o t a ke dr u g  
Artes u nate   
1 p o d or 2 tea ba gs  
3 ti mes per 
da y  
_ _: _ _ _ 
 a. m.    
_ _: _ _ _ 
 p. m.  
_ _: _ _ _ 
 p. m.  
 
 
 
 
D a y  
D ate  
N u m ber 
of  
Artes u n
ate te a 
b a g or 
p o d  
Ti me of D ose  
N u m ber 
of  
Artes u n at
e te a b a g 
or p o d  
Ti me of D ose  
N u m ber of  
Artes u n ate 
te a b a g or 
p o d  
Ti me of D ose  
1 
 
_ 
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 8 
 
5 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
6 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
7 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
8 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
9 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 0 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 1 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 2 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 3 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
1 4 
 
_  
_ _ _: _ _ _   □ a. m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
_  
_ _ _: _ _ _   □ p . m. 
□ D ose n ot ta ke n  
W h y: _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
Partici pa nt/ Care gi ver Si g nat ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
Date: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
5 9 
 
 
 
 
 
F O R S T U D Y T E A M U S E O N L Y
Staff I nitials:
D ate Dis pe nse d:
Date Ret ur ne d:
# pills/ca ps/ta bs dis pe nse d:
# pills/ca ps/ta bs ret ur ne d:
# pills/ca ps/ta bs t hat s ho uld ha ve bee n ta ke n:
Discre pa nc y N otes:


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 0 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 1 
 
 
A P P E N DI X D: T E L E H E A L T H T RI A G E A N D D RI V E/ T H R O U G H W A L K -I N 
E N R O L L M E N T  
 
 
 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 2 
 
A P P E N DI X E: G E T W E L L L O O P/ C E N T R A LI Z E D C O VI D -1 9 T E L E H E A L T H A T U K 
( C T U) A L G O RI T H M 
 
 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 3 
 
A P P E N DI X F: C U R R E N T R E C R UI T M E N T S T R A T E G Y A N D S C H E M A TI C F O R 
I N T A K E A N D C O N S E N T F O R R E S E A R C H A T R E S E A R C H D E SI G N A T E D C LI NIC 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 4 
 
P A TI E N T F L O W F O R I N T A K E I N T O I D C LI NI C 
 
 
 
 
 


I M P: Arte misi a a n n u a , Artes u n ate, C a m ost at mesil ate, Iver mecti n,           
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                           
A me n d me nt 4 A u g ust 2 8,  2 0 2 0  
 
                                                      
6 5 
 
A P P E N DI X G : T O XI CI T Y G R A DI N G S C A L E S F O R D E T E R MI NI N G S E V E RI T Y O F 
A D V E R S E E V E N T S  
 
htt ps:// w w w. niai d. ni h. g o v/researc h/ d mi d -safet y-re p orti n g- p har mac o vi gila nce 
 
A D U L T T O XI CI T Y T A B L E S  
 
A B B R E VI A TI O N S : A b bre viati o ns utilize d i n t he Ta ble:  
 
U L N = U p per Li mit of N or mal L L N = L o wer Li mit of N or mal  
R x = T hera p y Re q = Re q uire d  
M o d = M o derate I V  = I ntra ve n o us  
A D L = Acti vities of Dail y Li vi n g Dec = Decrease d  
 
E S TI M A TI N G S E V E RI T Y G R A D E  
 
F or a b n or malities N O T f o u n d else w here i n t he T o xicit y Ta bles use t he scale bel o w t o esti mate 
gra de of se verit y:  
 
G R A D E 1 Mil d  
Tra nsie nt or mil d disc o mf ort (< 4 8 h o urs); n o me dical 
i nter ve nti o n/t hera p y re q uire d  
 
G R A D E 2 M o der ate  
Mil d t o m o derate li mitati o n i n acti vit y - s o me assista nce ma y be 
nee de d; n o or mi ni mal me dical i nter ve nti o n/t hera p y re q uire d  
 
G R A D E 3 Se vere  
Mar ke d li mitati o n i n acti vit y, s o me assista nce us uall y re q uire d; 
me dical i nter ve nti o n/t hera p y re q uire d, h os pitalizati o ns p ossi ble  
 
G R A D E 4 Life -t hre ate ni n g E xtre me li mitati o n i n acti vit y, si g nifica nt assista nce re q uire d; 
si g nifica nt me dical i nter ve nti o n/t hera p y re q uire d, h os pitalizati o n or 
h os pice care pr o ba ble  
 
S E RI O U S O R LI F E -T H R E A T E NI N G A Es  
 
A N Y cli nical e ve nt dee me d b y t he cli nicia n t o be seri o us or lif e-t hreate ni n g s h o ul d be 
c o nsi dere d a gra de 4 e ve nt. Cli nical e ve nts c o nsi dere d t o be seri o us or life- t hreate ni n g i ncl u de, 
b ut are n ot li mite d t o seiz ures, c o ma, teta n y, dia betic ket oaci d osis, disse mi nate d i ntra vasc ular 
c oa g ulati o n, diff use petec hiae, paral ysis, ac ute ps yc h osis, se vere de pressi o n.  


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 6 
 
 
H E M A T O L O G Y  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
He m o gl o bi n  
9. 5 -1 0. 5  g/ d L  
8. 0 -9. 4  g/ d L  
6. 5 -7. 9  g/ d L  
< 6. 5  g/ d L  
A bs ol ute Ne utr o p hil 
C o u nt  
1 0 0 0 -1 5 0 0/ m m 3   
7 5 0 -9 9 9/ m m 3  
5 0 0 -7 4 9/ m m 3   
< 5 0 0/ m m 3   
Platelets  
7 5, 0 0 0 -9 9, 9 9 9/ m m 3   
5 0, 0 0 0 -7 4, 9 9 9/ m m 3 
2 0, 0 0 0 -4 9, 9 9 9/ m m 3 
< 2 0, 0 0 0/ m m 3  
W B Cs  
> 1 3, 0 0 0/ m m 3   
1 3, 0 0 0 -1 5, 0 0 0/ m m 3 
1 5, 0 0 0 -3 0, 0 0 0/ m m 3   
> 3 0, 0 0 0 or 
< 1, 0 0 0/ m m 3   
P ol y m or p h o n uclear 
Le uc oc ytes + Ba n d 
Cells  
> 8 0 %  
9 0 -9 5 %  
> 9 5 %  
----------  
A b n or mal Fi bri n o ge n  
L o w:  
1 0 0- 2 0 0 m g/ d L  
Hi g h:  
4 0 0- 6 0 0 m g/ d L  
L o w:  
< 1 0 0 m g/ d L  
Hi g h:  
> 6 0 0 m g/ d L  
L o w:  
< 5 0 m g/ d L  
----------  
Fi bri n o ge n 
ass ociate d wit h gr oss 
blee di n g or wit h 
disse mi nate d 
c oa g ulati o n  
Fi bri n S plit Pr o d uct  
2 0 -4 0  µ g/ m L  
4 1 -5 0  µ g/ m L  
5 1 -6 0  µ g/ m L  
> 6 0  µ g/ m L  
Pr ot hr o m bi n Ti me ( P T)  1. 0 1 -1. 2 5 ×  U L N  
1. 2 6 -1. 5  ×  U L N  
1. 5 1 -3. 0  ×  U L N  
> 3  ×  U L N  
Acti vate d Partial 
T hr o m b o plasti n ( A P P T)  
1. 0 1 -1. 6 6  ×  U L N  
1. 6 7 -2. 3 3  ×  U L N  
2. 3 4 -3  ×  U L N  
> 3  ×  U L N  
Met he m o gl o bi n  
5. 0 -9. 9 %  
1 0. 0 -1 4. 9 %  
1 5. 0 -1 9. 9 %  
> 2 0. 0 %  


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 7 
 
C H E MI S T RI E S  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
H y p o natrae mia  
1 3 0 -1 3 5 m E q/ L  1 2 3 -1 2 9 m E q/ L  1 1 6 -1 2 2 m E q/ L  
< 1 1 6 m E q/ L or a b n or mal s o di u m 
wit h me ntal stat us c ha n ges or 
seiz ures  
H y per natrae mia  
1 4 6 -1 5 0 m E q/ L  1 5 1 -1 5 7 m E q/ L  1 5 8 -1 6 5 m E q/ L  
> 1 6 5 m E q/ L or a b n or mal s o di u m 
wit h me ntal stat us c ha n ges or 
seiz ures  
H y p o kalae mia  
3. 0 - 3. 4 m E q/ L  2. 5 - 2. 9 m E q/ L  2. 0 - 2. 4 m E q/ L  
or i nte nsi ve re place me nt 
t hera p y or h os pitalizati o n 
re q uire d  
< 2. 0 m E q/ L or a b n or mal p otassi u m 
wit h paresis, ile us or life -t hreate ni n g 
arr h yt h mia  
H y per kalae mia  
5. 6 - 6. 0 m E q/ L  6. 1 - 6. 5 m E q/ L  6. 6 - 7. 0 m E q/l  
> 7. 0 m E q/ L or a b n or mal p otassi u m 
wit h life -t hreate ni n g arr h yt h mia  
H y p o gl ycae mia  
5 5 -6 4 m g/ d L  
4 0 -5 4 m g/ d L  
3 0 -3 9 m g/ d L  
< 3 0 m g/ d L or a b n or mal gl uc ose wit h 
me ntal stat us c ha n ges or c o ma  
H y per gl ycae mia  
( n o n-fasti n g a n d n o 
pri or dia betes)  
1 1 6 - 1 6 0 
m g/ d L  
1 6 1 - 2 5 0 m g/ d L  2 5 1 - 5 0 0 m g/ d L  
> 5 0 0 m g/ d L or a b n or mal gl uc ose 
wit h ket oaci d osis  
or seiz ures  
H y p ocalcae mia  
(c orrecte d f or 
al b u mi n)  
8. 4 - 7. 8 m g/ d L  7. 7 - 7. 0 m g/ d L  6. 9 - 6. 1 m g/ d L  
< 6. 1 m g/ d L or a b n or mal calci u m 
wit h life t hreate ni n g arr h yt h mia or 
teta n y  
H y percalcae mia 
(c orrect f or 
al b u mi n)  
1 0. 6 - 1 1. 5 
m g/ d L  
1 1. 6 - 1 2. 5 
m g/ d L  
1 2. 6 - 1 3. 5 m g/ d L  
> 1 3. 5 m g/ d L or a b n or mal calci u m 
wit h life -t hreate ni n g arr h yt h mia  
H y p o ma g nesae mia  
1. 4 - 1. 2 m E q/ L  1. 1 - 0. 9 m E q/ L  0. 8 - 0. 6 m E q/ L  
< 0. 6 m E q/ L or a b n or mal ma g nesi u m 
wit h life -t hreate ni n g arr h yt h mia  
H y p o p h os p hatae mia  2. 0 - 2. 4 m g/ d L  1. 5 -1. 9 m g/ d L 
or  
re place me nt R x 
re q uire d  
1. 0 -1. 4 m g/ d L  
i nte nsi ve t hera p y  
or h os pitalizati o n re q uire d  
< 1. 0 m g/ d L or a b n or mal p h os p hate 
wit h life -t hreate ni n g arr h yt h mia  
H y per bilir u bi nae mia  1. 1 - 1. 5 x U L N  1. 6 - 2. 5 x U L N  2. 6 - 5 x U L N  
> 5 x U L N  
B U N  
1. 2 5 - 2. 5 x 
2. 6 - 5 x U L N  
5. 1 - 1 0 x U L N  
> 1 0 x U L N  


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 8 
 
C H E MI S T RI E S  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
U L N  
H y per uricae mia 
( uric aci d)  
7. 5 –  1 0. 0 
m g/ d L  
1 0. 1 –  1 2. 0 
m g/ d L  
1 2. 1 –  1 5. 0 m g/ d L  
> 1 5. 0 m g/ d L  
Creati ni ne  
1. 1 - 1. 5 x U L N  1. 6 - 3. 0 x U L N  3. 1 - 6 x U L N  
> 6 x U L N or dial ysis re q uire d  
 
 
 
 
 
E N Z Y M E S  
 
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
A S T ( S G O T)  
1. 2 5 -2. 5  ×  U L N  2. 6 -5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
A L T ( S G P T)  
1. 2 5 -2. 5  ×  U L N  2. 6 - 5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
G G T  
1. 2 5 -2. 5  ×  U L N  2. 6 -5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
Al kali ne 
P h os p hatase  
1. 2 5 -2. 
5  ×  U L N  
1. 6 -5  ×  U L N  
5. 1 -1 0  ×  U L N  
> 1 0  ×  U L N  
A m ylase  
1. 1 -1. 5  ×  U L N  
1. 6 -2. 0  ×  U L N  
2. 1 -5. 0  ×  U L N  
> 5. 1  ×  U L N  
Li pase  
1. 1 -1. 5  ×  U L N  
1. 6 -2. 0  ×  U L N  
2. 1 -5. 0  ×  U L N  
> 5. 1  ×  U L N  
 
U RI N A L Y SI S  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Pr otei n uria  
1 + or 2 0 0 m g - 1  g 
l oss/ da y  
2 -3 + or 1 -2  g 
l oss/ da y  
4 + or 2 -3. 5  g l oss/ da y  
ne p hr otic s y n dr o me or  
> 3. 5  g l oss/ da y  
He mat uria  
micr osc o pic o nl y  
< 1 0 r bc/ h pf  
gr oss, n o cl ots  
> 1 0 r bc/ h pf  
gr oss, wit h or wit h o ut 
cl ots, O R re d bl o o d 
cell casts  
o bstr ucti ve or re q uire d tra nsf usi o n  
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
6 9 
 
 
C A R DI O V A S C U L A R  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Car diac R h yt h m  
 
as y m pt o matic, 
tra nsie nt si g ns, 
n o R x re q uire d  
rec urre nt/ persiste nt; 
s y m pt o matic R x 
re q uire d  
u nsta ble d ysr h yt h mia; h os pitalizati o n 
a n d treat me nt re q uire d  
H y perte nsi o n  
tra nsie nt i ncrease 
> 2 0 m m/ H g; n o 
treat me nt  
rec urre nt, 
c hr o nic i ncrease 
> 2 0 m m/ H g. 
/treat me nt 
re q uire d  
ac ute treat me nt 
re q uire d; o ut patie nt 
treat me nt or 
h os pitalizati o n 
p ossi ble  
e n d or ga n da ma ge or h os pitalizati o n 
re q uire d  
H y p ote nsi o n  
tra nsie nt ort h ostatic 
h y p ote nsi o n wit h heart 
rate i ncrease d b y < 2 0 
beat/ mi n or decrease d 
b y < 1 0 m m H g s yst olic 
B P, N o treat me nt 
re q uire d  
s y m pt o ms d ue t o 
ort h ostatic 
h y p ote nsi o n or 
B P decrease d b y 
< 2 0 m m H g 
s yst olic; 
c orrecta ble wit h 
oral fl ui d 
treat me nt  
re q uires I V fl ui ds; n o 
h os pitalizati o n 
re q uire d  
mea n arterial press ure < 6 0 m m/ H g or 
e n d or ga n da ma ge or s h oc k; re q uires 
h os pitalizati o n a n d vas o press or 
treat me nt  
Pericar ditis  
mi ni mal eff usi o n  
mil d/ m o derate 
as y m pt o matic 
eff usi o n, n o 
treat me nt  
s y m pt o matic 
eff usi o n; pai n; E C G 
c ha n ges  
ta m p o na de; pericar di oce ntesis or 
s ur ger y re q uire d  
He m orr ha ge, 
Bl o o d L oss  
micr osc o pic/ occ ult  
mil d, n o 
tra nsf usi o n  
gr oss bl o o d l oss; 1 -2 
u nits tra nsf use d  
massi ve bl o o d l oss; > 3 u nits 
tra nsf use d  
Electr ocar di o gra m 
Q T c orrecte d 
i nter val pr ol o n ge d  
 
A vera ge Q Tc 
4 8 1 - 5 0 0 ms 
A vera ge Q Tc > = 5 0 1 
ms; > 6 0 ms c ha n ge 
fr o m baseli ne 
T orsa de de p oi ntes; p ol y m or p hic 
ve ntric ular tac h ycar dia; 
si g ns/s y m pt o ms of seri o us arr h yt h mia 
Si n us tac h ycar dia  As y m pt o matic, 
i nter ve nti o n n ot 
S y m pt o matic; 
n o n- ur ge nt 
S u pra ve ntric ular 
tac h ycar dia 
S y m pt o matic, ur ge nt i nter ve nti o n 
i n dicate d Life 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
7 0 
 
i n dicate d 
me dical 
i nter ve nti o n 
i n dicate d Ur ge nt 
me dical 
i nter ve nti o n 
i n dicate d  
As y m pt o matic, 
i nter ve nti o n n ot 
i n dicate d N o n- ur ge nt 
me dical i nter ve nti o n 
i n dicate d -t hreate ni n g 
c o nse q ue nc es 
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
7 1 
 
R E S PI R A T O R Y   
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
C o u g h  
tra nsie nt- n o 
treat me nt  
persiste nt c o u g h; 
treat me nt res p o nsi ve  
Par o x ys mal c o u g h; 
u nc o ntr olle d wit h 
treat me nt  
 
Br o nc h os pas m, 
Ac ute  
tra nsie nt; n o 
treat me nt; 7 0 % - 
8 0 % F E V 1 of pea k 
fl o w  
re q uires treat me nt; 
n or malizes wit h 
br o nc h o dilat or; F E V 1 
5 0 % - 7 0 % ( of pea k 
fl o w)  
n o n or malizati o n wit h 
br o nc h o dilat or; F E V 1 2 5 % 
- 5 0 % of pea k fl o w; or 
retracti o ns prese nt  
c ya n osis: F E V 1 < 2 5 % of pea k  
fl o w or i nt u bati o n necessar y  
D ys p n oea  
d ys p n oea o n e xerti o n  d ys p n oea wit h n or mal 
acti vit y  
d ys p n oea at rest  
d ys p n oea re q uiri n g O x y ge n 
t hera p y  
A d ult res pirat or y 
distress  
s y n dr o me 
- 
- 
Prese nt wit h ra di ol o gic  
fi n di n gs; i nt u bati o n n ot 
i n dicate d 
Life -t hreate ni n g res pirat or y or 
he m o d y na mic c o m pr o mise; 
i nt u bati o n or ur ge nt 
i nter ve nti o n i n dicate d 
P ul m o nar y 
he m orr ha ge 
 
Mil d s y m pt o ms; 
i nter ve nti o n 
n ot i n dicate d 
M o derate s y m pt o ms; 
i n vasi ve 
i nter ve nti o n n ot 
i n dicate d 
 
Tra nsf usi o n i n dicate d;  
i n vasi ve i nter ve nti o n 
i n dicate d; h os pitalizati o n 
Life -t hreate ni n g 
c o nse q ue nces; i nt u bati o n or 
ur ge nt i nter ve nti o n i n dicate d  
P ne u m o nitis  
o x y ge n i n dicate d 
 
As y m pt o matic; 
cli nical or 
dia g n ostic 
o bser vati o ns o nl y; 
i nter ve nti o n n ot 
i n dicate d 
S y m pt o matic; me dical  
i nter ve nti o n i n dicate d; 
li miti n g i nstr u me ntal 
A D L  
Se vere s y m pt o ms; li miti n g 
self 
care A D L; 
Life -t hreate ni n g res pirat or y 
c o m pr o mise; ur ge nt 
i nter ve nti o n i n dicate d (e. g., 
trac he ot o m y or i nt u bati o n) 
L u n g i nfecti o n - 
 
M o derate s y m pt o ms; 
oral i nter ve nti o n 
i n dicate d (e. g., 
a nti bi otic, a ntif u n gal, 
or a nti viral)  
I V a nti bi otic, a ntif u n gal, or 
a nti viral i nter ve nti o n 
i n dicate d; i n vasi ve 
i nter ve nti o n i n dicate d 
Life -t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
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G A S T R OI N T E S TI N A L  
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Na usea  
mil d or tra nsie nt; 
mai ntai ns reas o na ble 
i nta ke  
m o derate 
disc o mf ort; i nta ke 
decrease d 
si g nifica ntl y; s o me 
acti vit y li mite d  
n o si g nifica nt i nta ke; re q uires I V 
fl ui ds  
h os pitalizati o n re q uire d;  
V o miti n g  
1 e pis o de i n 2 4 h o urs  
2 -5 e pis o des i n 2 4 
h o urs  
> 6 e pis o des i n 2 4 h o urs or 
nee di n g I V fl ui ds  
p h ysi ol o gic c o nse q ue nces 
re q uiri n g h os pitalizati o n or 
re q uiri n g pare nteral n utriti o n  
C o nsti pati o n  re q uiri n g st o ol 
s ofte ner or dietar y 
m o dificati o n  
re q uiri n g la xati ves  
o bsti pati o n re q uiri n g ma n ual 
e vac uati o n or e ne ma  
o bstr ucti o n or t o xic 
me gac ol o n  
Diarr hea  
mil d or tra nsie nt; 3 -4 
l o ose st o ols/ da y or 
mil d diarr hea last < 1 
wee k  
m o derate or 
persiste nt; 5 - 7 l o ose 
st o ols/ da y or 
diarr hea lasti n g > 1 
wee k  
> 7 l o ose st o ols/ da y or bl o o d y 
diarr hea; or ort h ostatic 
h y p ote nsi o n or electr ol yte 
i m bala nce or > 2 L I V fl ui ds 
re q uire d  
h y p ote nsi ve s h oc k or 
p h ysi ol o gic c o nse q ue nces 
re q uiri n g h os pitalizati o n  
Oral 
Disc o mf ort/  
D ys p ha gia  
mil d disc o mf ort; n o 
diffic ult y s wall o wi n g  
s o me li mits o n 
eati n g/ dri n ki n g  
eati n g/tal ki n g ver y li mite d; 
u na ble t o s wall o w s oli d f o o ds  
u na ble t o dri n k fl ui ds; 
re q uires I V fl ui ds  


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
7 3 
 
N E U R O L O GI C A L   
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Ne ur o -Cere bellar  
sli g ht i nc o or di nati o n 
d ys dia d oc h o ki nesis  
i nte nti o n tre m or, 
d ys metria, sl urre d 
s peec h; n ysta g m us  
l oc o m ot or ata xia  
i nca pacitate d  
Ps yc hiatric  
mil d a n xiet y or 
de pressi o n  
m o derate a n xiet y or 
de pressi o n; t hera p y 
re q uire d; c ha n ge i n 
n or mal r o uti ne  
se vere m o o d c ha n ges 
re q uiri n g t hera p y; or 
s uici dal i deati o n; or 
a g gressi ve i deati o n  
ac ute ps yc h osis re q uiri n g 
h os pitalizati o n; or s uici dal 
gest ure/atte m pt or 
hall uci nati o ns  
M uscle Stre n gt h  
s u bjecti ve wea k ness / 
n o o bjecti ve 
s y m pt o ms/ si g ns  
mil d o bjecti ve 
si g ns/s y m pt o ms/ n o 
decrease i n f u ncti o n  
o bjecti ve wea k ness 
f u ncti o n li mite d  
paral ysis  
Parest hesia 
( b ur ni n g, ti n gli n g, 
etc.)  
mil d disc o mf ort; n o 
treat me nt re q uire d  
m o d erate disc o mf ort; 
n o n- narc otic a nal gesia 
re q uire d  
se vere disc o mf ort; or 
narc otic a nal gesia 
re q uire d wit h 
s y m pt o matic 
i m pr o ve me nt  
i nca pacitati n g; or n ot 
res p o nsi ve t o narc otic 
a nal gesia  
Ne ur o -se ns or y  
mil d i m pair me nt i n 
se nsati o n ( decrease d 
se nsati o n, e. g., 
vi brat or y, pi n pric k, 
h ot/c ol d i n great t oes) 
i n f ocal area or 
s y m metrical 
distri b uti o n; or c ha n ge 
i n taste, s mell, visi o n 
a n d/ or heari n g  
m o derate i m pair me nt 
( m o d decrease d 
se nsati o n, e. g., vi brat or y, 
pi n pric k, h ot/c ol d t o 
a n kles) a n d/ or j oi nt 
p ositi o n or mil d 
i m pair me nt t hat is n ot 
s y m metrical  
se vere i m pair me nt 
( decrease d or l oss of 
se nsati o n t o k nees or 
wrists) or l oss of 
se nsati o n of at least 
m o d de gree i n 
m ulti ple differe nt 
b o d y areas (i.e., u p pe r 
a n d l o wer e xtre mities)  
se ns or y l oss i n v ol ves li m bs 
a n d tr u n k; paral ysis; or 
seiz ures  


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                                                                            
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
7 4 
 
M U S C U L O S K E L E T A L   
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Art hral gia (j oi nt pai n)  
mil d pai n n ot 
i nterferi n g wit h 
f u ncti o n  
m o derate pai n, a nal gesics 
a n d/ or pai n i nterferi n g 
wit h f u ncti o n b ut n ot wit h 
acti vities of dail y li vi n g  
se vere pai n; pai n a n d/ or 
a nal gesics i nterferi n g 
wit h acti vities of dail y 
li vi n g  
disa bli n g pai n  
Art hritis  
mil d pai n wit h 
i nfla m mati o n, 
er yt he ma or j oi nt 
s welli n g – b ut n ot 
i nterferi n g wit h 
f u ncti o n  
m o derate pai n wit h 
i nfla m mati o n, er yt he ma 
or j oi nt s welli n g – 
i nterferi n g wit h f u ncti o n, 
b ut n ot wit h acti vities of 
dail y li vi n g  
se vere pai n wit h 
i nfla m mati o n, eryt he ma 
or j oi nt s welli n g –a n d 
i nterferi n g wit h acti vities 
of dail y li vi n g  
per ma ne nt a n d/ or 
disa bli n g j oi nt 
destr ucti o n  
M yal gia  
m yal gia  wit h  n o  
li mitati o n of  
acti vit y  
m uscle te n der ness (at 
ot her t ha n i njecti o n site) 
or wit h m o derate 
i m pair me nt of activit y  
se vere m uscle te n der ness 
wit h mar ke d i m pair me nt 
of acti vit y  
fra n k m y o necr osis  


S KI N  
 
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
M uc oc uta ne o us  
er yt he ma; pr urit us  diff use, mac ul o 
pa p ular ras h, dr y 
des q ua mati o n  
vesic ulati o n or 
m oist 
des q ua mati o n or 
ulcerati o n  
e xf oliati ve der matitis, 
m uc o us me m bra ne 
i n v ol ve me nt or er yt he ma, 
m ultif or me or s us pecte d 
Ste ve ns-J o h ns o n or 
necr osis re q uiri n g 
s ur ger y  
I n d urati o n  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
Er yt he ma  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
E de ma  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
Ras h at I njecti o n 
Site  
< 1 5  m m  
1 5 -3 0  m m  
> 3 0  m m  
 
Pr urit us  
sli g ht itc hi n g at 
i njecti o n site  
m o derate itc hi n g 
at i njecti o n 
e xtre mit y  
itc hi n g o ver 
e ntire b o d y  
 
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
S Y S T E MI C  
 
 
 
 
 
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Aller gic Reacti o n  pr urit us wit h o ut 
ras h  
l ocalize d urticaria  ge neralize d 
urticaria; 
a n gi oe de ma  
a na p h yla xis  
Hea dac he  
mil d, n o treat me nt 
re q uire d  
tra nsie nt, 
m o derate; 
treat me nt 
re q uire d  
se vere; res p o n ds 
t o i nitial narc otic 
t hera p y  
i ntracta ble; re q uires 
re peate d narc otic t hera p y  
Fe ver: oral  
3 7. 5 - 3 8. 5 C  
or  
1 0 0. 0 - 1 0 1. 5 F  
3 8. 6 - 3 9. 5 C or  
1 0 1. 6 - 1 0 2. 9 F  
3 9. 6 - 4 0. 5 C or  
1 0 3 - 1 0 5 F  
> 4 0 C  
or  
> 1 0 5 F  
Fati g ue  
n or mal acti vit y 
re d uce d < 4 8 
h o urs  
n or mal acti vit y 
decrease d 2 5 - 
5 0 % > 4 8 h o urs  
n or mal acti vit y 
decrease d > 5 0 % 
ca n’t w or k  
u na ble t o care f or self  
I nfectio ns  a n d 
i nfestati o ns - 
Ot her,  
As y m pt o matic or 
mil d s y m pt o ms; 
cli nical or 
dia g n ostic 
o bser vati o ns o nl y; 
i nter ve nti o n n ot 
i n dicate d 
M o derate; 
mi ni mal, l ocal or 
n o ni n vasi ve 
i nter ve nti o n 
i n dicate d; 
li miti n g a ge 
a p pr o priate 
i nstr u me ntal A D L 
Se vere or 
me dicall y 
si g nifica nt b ut 
n ot i m me diatel y 
life t hreate ni n g; 
h os pitalizati o n 
or pr ol o n gati o n 
of e xisti n g 
h os pitalizati o n 
i n dicate d; 
li miti n g self-care 
A D L  
Life -t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d 
Se psis  
- 
- 
Bl o o d c ult ure 
p ositi ve wit h 
si g ns or 
s y m pt o ms; 
treat me nt 
i n dicate d 
Life -t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d 
Aller gic reacti o n  
 
S yste mic 
i nter ve nti o n n ot 
i n dicate d 
 
Oral i nter ve nti o n 
i n dicate d 
Br o nc h os pas m;  
h os pitalizati o n 
i n dicate d f or 
cli nical 
se q uelae; 
i ntra ve n o us 
i nter ve nti o n 
i n dicate d 
 
Life -t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d 
 
A na p h yla xis   
 
- 
- 
S y m pt o matic 
br o nc h os pas m, 
wit h or wit h o ut 
urticaria;  
pare nteral 
i nter ve nti o n 
i n dicate d; 
aller g y-relate d 
Life -t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
e de ma/a n gi oe de
ma;  
h y p ote nsi o n 
 
 
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
A P P E N DI X H: O R D E RI N G  I N S T R U C TI ON S F O R A R M E, A R T E MI LI F E T E A O R C O F F E E  
 
 
T he i nf or mati o n f or s u p pl y of Arte misia  a n n ua is as f oll o ws:  
Baes ma n Distri b ut ors  
4 4 7 7 Re y n ol ds dri ve 
Hilliar d, O hi o 4 3 0 2 6 
C o ntact: T baes ma n @ baes ma n.c o m   
 
Rec or d of Re q uest f or Ar m E, M C C -C O VI D - 0 1-P M C cli nical trial  
 
O V E R NI G H T S HI P M E N T T O:  
Na me: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
A d dress: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
C o ntact P h o ne N u m ber: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
Dis pe nse:  
  C offee: Dis pe nse 4 2 p o ds ( 4 5 0 m g) 
  P o d c offee ma ker (if patie nt d oes n ot ha ve a p o d c offee ma ker)  
O R  
  Tea: Dis pe nse 8 4  tea ba gs (2 2 5 m g) 
 
Or dere d b y: 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _                          _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
St u d y C o or di nat or   
  
  
  
  
  
 
Date  
 
 
E nter data i nt o p ortal as descri be d bel o w.  
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
S C R E E N S H O T S O F O R D E RI N G P O R T A L  
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0 
 
                                                      
 
 


I M P: Hy dr oxyc hl or o q ui ne S ulf ate & Azit hr o myci n & C a m ost at mesil ate                           
                
          
St u dy #: M C C -2 0 - C O VI D-0 1 -P M C  
                                        
Versi o n 3,  J u ne 1 9 , 2 0 2 0