Randomized Comparison of Combination Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone for the Treatment of Confirmed COVID-19
Phase: PHASE2
Conditions: SARS-CoV-2, COVID-19
Sponsor: Rutgers, The State University of New Jersey

Official Title:
Randomized Comparison of Combination Azithromycin
and Hydroxychloroquine vs. Hydroxychloroquine Alone for
the Treatment of Confirmed COVID-19
NCT number:
04336332
Document Type:
Protocol
Date of the
Document:
0s10812020

INTERVENTIONAL
RESEARCH PROTOCOL TEMPLATE
. Title of ProJect:
I 
Randomieed Comparison of Cornbination Aaithromycin r
Hydroxydhloioquine vs. Hydroxychloroquine Alone for the Treatment of
Protocol Version and Date:
Version 6.0: 08-May-2024
Page 1 o{tl8

Tahle of Contents
To Section: Hold CTRL + Click {Belour} To Follow Link in Blue
1,1 P-urBs$d$p*!$qiiCIt
12 ffegearph.gig{Uficqnce
1.5
1,8 $reimen-Asleq$eo
1.9 Dala Oqllestiqn
1.10 Timetablel$chedule of I
2.1 Reseafg,,h,Slaff,apd Quali.fi. atiqn*
2,2- ffi
2,_3 fresgurcesAysIgElg
?.4
4.1 $ubiect $election and Enrollment Considerations
4.2 Secondary Subiects
NHIk-ef.of-Subiects
$*npqr*t.S#np,*n[Fspxlption$
- H*p*ft .or.nie Sqr{ee,p{!d1q*c*c,mmnsnqqn.[eJ,,,S[|hifr t,tp
5.1 Health lnsurance Portabilitv and Accountabilitv Act (HIPAA)
5,2 family Edqcaliqnal Righ$",anS ?r'vecy Act {fES,PA)
5.3 Code of Federal Reoula$ons Title 45 Fart46 {Vulnerable Populations}
5.4 Seneral PatE Protpe$cn,RFeglathn I FPru.
5.5
6.3 Data $afety And Monitorina
6.5
Azithromycin and
hrTrmfrnentol
Prueld'18
4.3
4.4
4.5
4'6
4.7
Confinrred C0VID-19
Protocol Versbn Date: 08-lr4ay-2020
?,0 Pr{*pl,Mntl+Ctment
?.0 B*"*,p"*rclt*gg,p"*iiffig*;Snecimpns-nndlor Oats
s.0
9.0

1.,l Purposel$pecitic Aims
The puryose of this study is to explore llre efiicacy of Azithromycin and Hydrox
witr proven sARS4ov-2 infiection with symptoms consistentwith covlD-19.
A. Obiectlves
Frimary O$ec.tive:
Detennine cfrange in viral load at day 6 compared to baseline between two
COVID-l9 and a contemporaneous control group.
. 
Normalization of vital signs
r Time to discfiarge {if hospitalized}
r Assessment of agent loxieity as measured by standard metrics
r Colleclion of throat srabs and blood for viral load, presence of lgM or
. lf feasible on samples collected for quantitative PCR decrease in
oropharyngeal secre$ons)
" Measutss of cytokines in blood including lLS, lL-8, TNF, INF
We propose performing a three-arm randomiaed trial comparing the efficacy
hydroxychloroquine to the combination of hydroxychloroquine and azithromycin,
hydroxychloroquine regimen, which willserve as a contemporanesus Oay 1-6
eliminating detectable sARS-cov-2 on day 6 following the initiation of tre
determine which regimen is more efective.
l.? Research Significance
covlD-19, a respiratory disease caused by the novel sARS-coV-l virus, appeared in
late 2019 and has spread rapidly affoss the globe [1, 2]. This epidemic has rapidly
pandemic as declared by the vYHo [31. Experience with covlo-19 in china has
approximately 80% of patients present with mild disease however, their data suggests
fatality rate of 2.3o/o which can be as high as 8.0% in patients aged 70 to 79 years and 1
180 years of age [41. As of March 19, 2020, there are 2lg,r8g confirmed cases and g
wide
cf6). The rate of increase in new cases outside of China is exponential, putting health
world at risk for not being able to meet the demand for beds and intrensive care. Wth no
and a vaccine unlikely to be available for 12-18 manths, efiectivs treatments to
palients and serious hospi&lized patients are critically needed.
Chloroquine (an antimalarial drug) has been shown to inhibit the growth of $ARS-CoV-
clinicaltrialconducted in COVID-l9 patients in China, demonstrated a significant effect
clinical outsome and on viral clearance, compared to controls [6, {. Based on this work,
have recommended that patients diagnosed with COVID-IU having mild, moderate and
Secondary 0bjective:
r Time to resolution of symptams {symptom questionnaire)
. 
Change in the fever curve resulting in shorter time to afebrile for 48
antibodies
shedding (in
. 
Routine standard of care labs obtained as part of the care of these
such as
differentialwhile count, CRP, tr,oponin and LFTs will be analyzed for
trends
B. Hypotheses I Research Question(s)
in patients
s to treat
single agent
to a delayed
csntrol, in
in order to
China in
toa
that
overall case-
8% in patients
deaths world-
across the
at present,
symptomaiic
in vitro, [5]. A
chloroquine on
in China
cases of
Page i of if8

pnemonie and without contraindications to efrloruguine, be treated with s00 mg
for ten days [B].
twice a day
A group in France [SJ has recently reported on a completed clinical study substituting
roxychloroquine
(an analogue of chloroquine), which has been shown to have an anti-sARS-cov (aglnt
activity in vitro [10] a virus sharing significant homology with SARS-CgV-?. There is str
$ARS in 2002)
the safe$ profile of hydroxychloroquine is better than that of chloroquine altowing higher
dosing [11]
and fewer drug-drug intsraclions [12-161. ln this study, a total of 26 COVID-I$ patients
included in a
single arm trial receiving 600m9 of hydroxychloroquine po daily and their viral load in
swabs was tested daily in a hospital setiing. Depending on their clinical presentation, azithr
added to the keatment. Sixteen untreated patienk from a second center and caxes
in the protocol were included as controls. Presence and absence of virus at Day
to participate
considered lhe end point. Six patients were asymptornatic, 22 had upper
symptoms and eight had lower respiratory tract infection symptorns. Tweng cases were
in this study
and showed a significant reduction of the viral carriage al day six-post inclusion
to controls, and
those receiving
much lower average duralion of viral caniage than that reported in the unteated patients.
evidence that
wasalso
inclusion was
tract infection
7-191 added to
with detectable
be compared.
SARS-CoV-2
virus on day six [9]. Based on lhese results we propose performing a three-arm
trialcomparing
the efficacy of single agent hydroxychloroquine to the combinalion of hydroxychloroquine
azithromycin
as well as lo a grcup receiving a placebo, where initiation of hydroxychloroquine
may begin afier
viral sampling on day 6. The primary endpoint in this study is a measure of success in
detectable
SARS-CoV-2 on day 6 following the initiation of treatment {or in the case of delayed
clinical and
the initiation of supportive care). secondary endpoints will address questions
biologic endpoints. This trial is needed in order to determine if the addition of
to
hydroxychloroquine is superior in redueing viral load to hydroxychloroquine
At present,
hydrorychloroquine is one of only a handful of agents that have shown some promise in
covtD-
19. Determining the activi$ of azithromycin in combination with hydrcxychloroquine wou
be of benefii by
either discovering there is improved activi$, or by determining that there is little or no
tn
activity and therefore spare the logistics and expense of adding azithromycin to the
short-term placebo arm where the initiation of hydroxychloroquine can begin following
sample collection will allow hydroxychloroquine featment and a placebo featrnent amt
hydroxychloroquine alone, 8i14 had no evidence of yirus at day six. Aaithromycin
hydrorychloroquine was significantly more efficient for virus elimination with 0/6 patiel
assay with symptom$ consistent with COVID-19 such as a feyer of > 100.6. This study
efficacy of Azithromycin and Hydroxychloroquine in &is patient population. study pa
The use of a
6 virus level
This study will also provide a significant opportunlty to learn rnore about COVID-I$
through the compleiion of fte *Mies supportirq the seeondary endpoin*.
{.3 Reeearch Oesign and llllethods
This is a randomieed trial conducted by the Rutgers Cancer lnstitute of New Jersey and at
SlUniversity
Hospital Newark), which will prospectively enroll 160 patients with proven SARS-doV-2 i
ion by qPCR
evaluate the
will be
randomized to 'l ) Aztthrornycin and Hydroxychloroquine; 2) l-lydroxychloroquine alone; or
) placebo for 6
days followed by hydroxychloroquine. Trsetrnent with the investigational agents will
for 10 days.
Viral loads will he eollected to monitor response to treatment at baseline and on day 3
day 6.
0&May-2020
Page 4 o{48

A. Rssparch Proce&nes
i. StudyPnrcednm:
' Oats0- Screentng Mls#;
$ Obtain infonfied consentfortrial ewollmerrt
o Demqraphic data
o Medieal histrory
* Physicalexamination
o Vital signs {Sood pressure, heart rate, temperafire}
o Bocumentdisease severlty {mild, moderafi or sevire}
. 
Seventy Asse$ment Criteria
. 
Temp >100.5"F (i pon0
r Fatigue (i point)
. 
Cough (t poinil
r Shortrre$ sf breaft (1 point)
r Heart rab >90 BpM {A points)
. 
Respirabry rate > i4 breE*reSmin (2 poinb)
r Fulse Ox < g*% on Hrom air{3 po{nts}
r Blood pressure < 90160 (3 poinb)
seslg:
MildModeraie = &7 potnts
Severe = B-15 pointr
o Document locatianof palient {inpatierrt versu$ outpatient}
a Review eligibility criteria
c, Complete baseline COVID signs and symptorns questionnaire
r: Electrocardiogram" The eT corrected'intervai may be ci
Bazett's, Fridericia's, or Framingharn's forynula
. 
BaEett'* formula: eTc i eT/ {(RR in seconds}
' 
Fridericia's fornula: eTe = QTIRR^0.33)
-Framingham's formula: eTc = eT + 0.154 {1-RR}
* Labs: CECD, Fenitin, D-Dimer, LOH, CRp and Troponin (g ml-);
qregnancy test for women of childbearing potential
by either
or serum
the inlomred
(16 mL)
Arm 7:
(unless
by phone.
,r Concomitant medications {starling from the time the patient
consent)
o Collect research specimens: saliva, oropharynx swab and whole
,r Randomize study participant *rrough On0ori@
* Dispense study medication
o Prcvide educarion to patient cn how to complete piil diary and
Each subject will receive an electic themometer for use.
r rlealment perlod- Farfhnse studyparflcipants randamlzed to Arm
o Oays1-10
, ltuly participant doses self wittr prescribed study
inpatient)
' 
Assessment completed by Research Nurse. May be
r Complete fiollow-up COVID signs and
(Appendix D)
r Review of daily temperatures
. 
Reyiew of medication compliance
log.
Pags gof48
queslionnaire

. 
AdverSe events
. 
Record standard of care treatrnents andlor
a DaySor4andDay6
, 
Repeat phy*ical examination
. Labs: CBCD, Fenitin, D-Dirner, LDH, CRp and
prescribed
(8 mL) {Day 6
whole blood
by phone.
tplacebo),
by phone.
(Appendix
{8 mL) (Day 6
whole blood
6, willinitiate
(unless
by phone.
. 
Labs: CBCD, Fenitin, D-Dimer, LDH, CRF and Troponin
mLi
o Day 11-20 - Daily Follow-up
. 
Assessment completed by Research Nuse. May be
. 
Revierry of synrptoms
. 
Review of daily lemperatures
. 
Adverse events
' 
Record standard of care treatments andlor pracedures
r 
Treatmenf Perlod- For those stadypart:crpanfs randomlzed to Arm
o Days 1 -5
. 
Study participant doses self with prescribed slug
unle$s *npalient.
only)
. 
Gollect r**ardr specimens: galiva, oropharynx urab
(16 mL)
0 Day 1S {*l. t day)
. Repat physical examinatian
. 
Assessrnentmnnpleted by Research NurEe. May be
. 
Cornplete follow-up COVID signs and symptoms qur
D)
. 
Review of daily temperatures
. 
Review of medical*on mmpliance
. 
Adverseevents
. 
Record standard of care trealments and/or procedures
* DaySor4andDay0
. 
Repeatphysicalexaminatian
. Lahs: 6BCD, Fenitin, D,Oimer, LDH, CRp snd Tj
only)
. Coll*ct research specimens: saliva, oropharynx swab
(16 mL)
. 
lf patienl continues to have sympioms of COVID-19 on
Hydrorycfiloroquine sulfate fior home adminiskation.
o Day t0. 
Repeat physical examination
. 
l-abs: CBCD, Fenitin, O-Dimer, LOH, CRP and Troponin
* Sayll-15
. Study participant doses self wisr preseribed study
inpat$ent)
. 
A$sessment completed by Research Nurse. May be
. 
Complete follow-up COVID signs and
{Appendix CI}
" Review of daily temperatures
rnl-)
Prolocol Verkrn Dats: o&May-?0m
Page 6of i[8
questionnaire

r FoIIor-nF pertad for AIJArns
c weekty Foilor-up for Four {4) weeks {+/- one day} from ragt
. 
Assessment completed by Research lUur6e. MaV be
. 
Review of symptoms
, 
Review of daily temperatures
r 
Revienv of rnedication compliance
r Adverse events
r Record standard of care trealmen& andor
. Adverse events
, 
Record s&ndard of care treatmenb and/or procedures
once daily dosing to mmplete the original 10 days of
Hydroxych loroquine sulfate
O.ry,hydloxychloroquine sulfate tablet contains i00 mg of
which is the equivalent to 1SS mg base.
a Oay 15-40 - Baity Foltow-up
. 
Assessrnent cornpleted by Research Nurse. lltay be
. 
Review of symptorns
. 
Review cf daily temperatures
preouibed
,byphone.
of treatment
by phone.
by phone.
X 4 days
and resume
8lD dosing to
resume at
. 
Advgrse events
. 
Record strandard of c*e treatnrents and/or procedurer
o Monthly Foltow-up for Six {g} Months t+l. oneweek}
' 
Assessment completed by Rei*earch Nurse. May be
. 
Rerriew of syrnptoms
. 
Review of daily temperatures
. 
Adverse events
. 
Record standard of care treatments andlor procedures
2. Treafnent Plan:
" OosaSsardAdmimska&sr
Arm l: 
Hydroryctrtoroquine *ulf*te 200 rng po TID X 10 days
Azi*uomycin EOS rng po on gay trt*, follo!,/ed Ay 260 mg po
Am 3: 
Hydrorychloroquine sr$fate 200 mg po TID X 10 days
Am_3: Pl"Fbo Dlys i-0, bilovring viral sampling on day 6
Hydroryr*rloroquine sumati'eoc rW p, n"D; ro i"y.
. 
Oosa fi,fodrificafion;
o Hydrcxvchlomquine
" For grade 1 or 2 intolerabiltty: allow patient to hold one
as tolerated withsui adjustrnent
. 
For grade 3 or 4 toxicity: hold one dose and resume at
cornplete the original 10 days of dosing
. 
For second episode grade 3 or 4 toxic-ity: hold next dose
0&May-?0?t}
Page 7 of48

B.
For this study, dosing will be 200 mg TID PC x 10 day* with or without azithromycin
(depending on randcmiaation).
Take hydroqpcihloroguine *ufhfu tabkb wiilr a rneel or a glass of milk when permissible.
Azithromycin
For this study, dosing will be azithromycin 2 x 250 mg (500 mg) on Day l, foltored by 1 x
250 mg.dgily x 4 {o2 thru 5} wfth Hce 200 mg TtD pc x t['days trgi*ing on day 1
{depending on randomization).
Placebo
Arm 3 only. For this sfi,r{, participanls wil} be provided 30 placebo tahle& to maink}n ihe
blind betueen Ann 2 and Arm 3. Dosing will be placebo tablet x 3 daily (D1 thru 6).
Coaoornilan t Med i cations I Supportrve Guidellnes
Study participants can receive full supportive c*re therapies conounitanfy during *re
sttrdy" Conmmitant therapy includes any prescriplion nie*ications or over-the-c&rnter
preparations used by a patient Som s 7 days prior to the first dose of *tudy drug to the
end of treatnent visit. All concomitant therapy, including vitarnins, homxfrathikhe&al
remedies, nufiitbnalsupplements, rnust be recorded during the screeningand treafnent
geriod, starting from the dab of signature of informed consent, and ending at tlre Endof
Treatment (EOT) visit.
Subject Enrollm*nt
FatiEnts-who are eligible for lhe study will be enrolled in th* clinical tial affer trey provide
informed conrent for stu{ partieipation. A copy of ttre institution's IRB approvedinfurmed
consent will be on file at Rutgers Cancer lnstitrte af New Jersey's Offce of Human Research
$ervices (OHRS) before any participating instihrtians may enter patients.
$ites will register and enrcll patients thrcugh On0or@the Clinical Trials Management $ystem for
this stu{. Contact l}re Rutgers Cancer lnstlute of New Jelsey's OHRS Registration Desk (732)
2354745 if you have any queslicns about the Registration/Enrollmenl proc*ss.
. 
Registration: Any subject that has signed tlre consent \uill he entered into OnCore@. A Copy
of &e consentwill be uploaded into the Documenb section.
r Enrollmerrt Onca eligibility haE been confirmed, the completed, signed and dated eligibility
checklist will be uploaded inta the Documents secticn. On0ore@will randomhe the patient
and a sequence number (subject study lD) will be generaled atthe time of enrollment, this is
the point the palient is cursidered on sfirdy.
Patients will gg! start protocol treatment priorto registmtion.
Study Safety Assessmenta
The Principal lnvestigator is responsible for ensuring that all staff involved in the sfu{l are familiar
wifi the content of fris section.
1. 0efinitions:
r ,Adverse Events:
An adverse event is ltre development of an undesirable medical conditimr or he
deterioratisn of a pre-existing medical conditinn following o durirg exposure to a

phannaceutical product, whether considered causally related to the product. An
undesirable medical condition c.an be symptoms {e"g. nausea, chest pqin}, slqni {e.s.
kchycardia, entarged liver] or the abnoimar resu$s if an investigation {;.ii" G[rj1gry
findings, eleekocardiogram). ln clinical studies, an AE can include jn undesirable medical
condition.occurring at.any time,"including run-in or washout periods, even if no stuov
treatment has been administered. The tern AE is used to include both serious and non-
serious AEe"
. 
$erious Adverse Evenb:
A serious adverse event is an AE occuning durirg any sludy phase {i.e., screenirlg, run-
in, keatment, wash-out, follcw-up), at any doee of fie study-drugs that fulflls one ir more
of the following criteria:
* Results in death
a lsimrnediatelytife-threatening
o Reguires in-paiienl hospitalization or prolongafion of existing hospitslization
o Resulk in persistent or s$gni8cant disability or incapacity
* ls a mngenitsl abnormdig or birth defed
* ls an important medical event that rnay jeopardise &e patient or may ra$.rire rned-rcal
intrervention to prevent one of the outcomes listed above.
q: The causali$ of SAEs (their relatianship to all study treatmenUprocedures) will be
assessed by the investigator(s) and Eommunicated to the FDA via MedWatch form, if
applicabla.
Recording of Adverse Evenk
Non-serious adverse events and SAEs will be detennined from the time treakrentstarh and
up to and. including the 6*nonth follow-up period. All grade 3 or hlgher AEs will be recorded.
Grade 1 AEs do not need tro be recorded. After rvithdiawal from tdatment, subjects mrri U"
followed-up forall existing and new AEs for 180 calendar days afier *re last doie of trialdrug
andor unlilevent rcsolulion. All new AEs occuning during that period must be recorded (if
!AEs, they,must be reported to the CINJ Data Saiety n{onitoring Committee {HROC} ani
Rutgers IRB as per SOFs.). AEs will be recorded plr Cll-tU SO-ps_
All sludy*elated toxicities/ SAEs mu*t be followed unlil resolution, unless in &e Trealing
lnvestigator's opinion, the condition is unlikely to resolve due to tfre paliert's unCe*ying-
disease"
Reporting of $erisus Adverse Events
lnvestigators and other site personnel rnust inform the CINJ HROC and Rutgers IRB perthe
ctNJ soPs on the required brms. FDAwill be informed per sop, via a Medtt\ratch, of any
serious or unexpected adverse events fi.tat occur in accordance wisr the reporiing obligatiryrs
of 21 CFR 312.32. lt is lhe responsibility of the principal investigator to ompile all necessary
information and ensure that the FDA receives a report accordint to the FDAreporting
requirement timelines.
All SAEs meeling lhe criteria fcrexpedited reporling will be reported to the Rutgers IRB wit6in
the mandatred time fiames. All SAEs wittrin the sa,fety follow-up window 1e.g,, iithin 30 days
after the last dose of study rnedieations) established in the probcol will be repo*eU.
Page I of il8
2.
3.

Non-serior"ts adver*e aveffs and SAEs will be csllectBd frorn the time beatment siarls,
*roughas the heatnrsnt period and up to and includi,ng tfre 6-monfr fonwr-6p perloU. Afier
wi*ldra*al tromlrealment, subjecb must be followed-rip for all exlstirq anu new AEs for 2g
calendar days afier the last dose of trial drug and/or until event resoluiion. All new AEs
occuning during that period must be recorded (if SAEs, $ren they must be repryted to the
FDA as pertheir rlPortinS criteria)" Allstudy-relabd toxicitiesl $AEs must be followed unlil
resolution, unless.in the Treating lnvestigatoy's opinion, Sre eondition is unlikely to resolye
due to the patient's underlying disease.
4. Clinical $afety Assessments
r RecordinE of Aduerse Evenk
Non-serious adverse events and SAEswill be determined *orn the time the studydrug is
given, ftroughout the keatnent pedod and up to and including the 6*mont follow-up
p€riod. Allgrade 3 or higherAEswill be reeorded. Grade l-?AEs do not need to be
recorded- Afterwithdrawal from treatrnent, subjects must be followed-up for all existing
and new AEs for 2S calendar days after the last dose of trial drug and/or unlil event
resolution' Il i."*lF.t 1ecuning during that perM rnust be r*rird*U {if $AEs, they must
be reported to the CINJ Data Safety Monitaring Cornmittee (t-tROC) *U Rutters 16g re
per SOPs"). AEs willbe recorded perCINJ $Ops.
r Adverse Eyen& Based on S$sns and Symptoms
When wllecling AEt, ilre reaording of diagno*es is preferred (when possible) tio
recording a list of signs and symptams. How€ver, if a diagnosls is known and there are
other signs or symptoms that are not generally part of the diagnosis, the diagnosis and
each sign or symptom will be recorded separaiely.
. 
Vital Signs
Ternperature will be obtained fourlirnes a day {firstthing in AM, mldday, pM, and
bedtirne). $ignificant abnormalities will be recorded as an AE. Body temperahrre will be
measured in degrees Fehrenheit using an automated thennomebrwhieh will be provided
to &e patient.
5, Study Effcacy/Response Assessments
' 
Quanffiative PCR measurements of viral load at baseline, Day I and Day 6. Day 6
mea$urement mmparcd to haseline will serve as the study endpoint. Oiher response
uiteria used as secandary endpoinb include change in temperature curve over lirne,
change in measured cytokines {lL6} and impruvement in cliltical sympfms as
determined by clinician assessment and patienr questionnaire.
O. Oata Points
Case Report Forms
Completion of the eleclronic case raport forms (eCRFs) will be dqne in aecordan* wtth the
instruclions outlined h r5................-stu!v specific data capture ptan. xt eCRFs are considerred &re primary
dah collestion document fur *re study and are itored'in Onoore@ in a ronfJuntiJfo"nrl OnfV
key parsonnel who are delegated in the delegation of authorig log are permitted io *.X" enfies,
Page 10 of t8

changes, or conections in Sre eCRF. All users of OnCore@ willmnrplete user training, as required
or appropriab per regulations. An audit trail will be rnaintained aubmatically by fre eiCcron6 Cnf
management *ystrm.
Batr Points to be wllec&d:
r Baselinernedicalhistory
r Treatnentcomplianee
. Daily temperatures
r Syrnptorns of disease
r Adverse eyents
. 
Concornitantmedicalions
I Any siandard of care fieaknents or procedures to manage covlD-lg
Dete $ubmission Tlmeline emd Forms
Completion of eCRFs will occur within 72 hourc of study time point unless othenrise indicated.
Baselirre (pre-stufl) eCRFs (e.g., enrollmen{ medicaltristory, concomihnt meoications, *i,.iniu
be completed no later rhan 24 hours afier the start of treatnent.
E. Study Duration
Study participants will be keated for ten (1Q days and will then renrain on follow-up fcr up to S
monfrs after the coryqlqtion of treaimenl. ttre istimated time to complete ne entile stuU'y is a
months {Norember 2020}.
We witl acoountSor.all ttg f.atie$sregistered in tfre study. The number of pafien& who were not
evaluable, who died or withdrew before treatnent uas compteteo wi1 be spei*ned fh; dirfi*rs";
of follow-up tinre will be de*wibed and the number of patielrn hst to toilot-u, *il! b- ;ir*. ----'
F. Endpoints
Primary endpoint:
1' Change in virel load atday rix compared to baselinr between hydrorychloroquirne sulfate alone
and hydrcrychrdorquine zut*ate ph*s azithromycin to beat COVID-l9. I second consrnent
cornparison will evaluate change in viml load at day 6 benreen hydroxycfrlorcquine sutrbti
alone and a placebo.
1. Tine to resolution of symptoms qsympUrn ques$onnairel
2. Change in the fever curye resuhing in shortirtime to ate,'nrib for48 hours
3. lmprovement in vitalsigns
4. fime to discfrarge (if hospitalized)
5. Time to recovery (back to work, school eh...)
6. Assessment of igpnt toxhity as measured bi standard metrics
7. Collection of orcpharynx suiab and blood forvirat load and microbiome analysis
8. Decrease in-virus shedding (in nasopharyngealsecretions) and serology
9. Measures of rytokines in blood including'116, llg, TNF and lruf
10. Measuresof infammatory markers sudr asfenitin, O-Dlmer, CRP, Troponin and LDH
{.tl Preliminary Data
There is. dab supporting the antiviral activity of both hydroxychloroquine and azithromycin as sinqle
?qqn!, but not ntuch experience with lhe combination. ln a-recenty completed Uaf $i;a&n13 ;ih
covl0-l9 (n=14) received hydroxycfrloroquine alone at the same ds;e *"d"fr*qd.y iroimeu in tris
Protocol Versbn Date. 08*May-20?0
Faqe 11 of{S

studV' fq lhese patients' 8/14 had no detectable virus at day 6 by pCR quantification. tn a smaller
groyp of six patients receiving the combination of hydroxycnldroquine tnd;iih;;ycin at thE doses
and frequency qropose! in this study, 6/6 had no deiectable virus at day 6 by pcn qiantrnca$on. lt is
this very preliminary, pilot observation in a very small number ot pariinis ih"a*;;;;;i #;;;j';;
randsmized that will he evaluated in this larger frospective randomized study.-
1.5 $ampl* $ize Justification
Randomized cliriical trial cornparing hydroxychloroquine with or without azithromycin in patients with
the COVID-'|9 disease, with the addition of a third arm with a placebo and delayed hydroxychloroquine.
Here we follow Gaubet et al. [9t in using, as a primery endpoint, absence of virat "vld"nr" 
of dlsease
six days following slart of teatment. In that study (Table 3 of ref g), there were 14 patients treated with
hydroxychloroquine alone, and 8/14 {57"1 percent} of them were virus-free at 6 days. There were six
patients keated with bot! hydroxychlorcquine plus azithromycin, and all six {100%i u€re virus-free at
6 days. ln a third group of patients with no hydroxychloroquine, there were I6 patients, of whom Z (12"i
percent) were virus-fee 1t 6 days. We propose a three*arm irial as foilows: 'n* i t*iA + g2), Arm
2 {Hca abne}, and fum 3 (derayed Hce}. with patients randomized 2:2;1.
The primary outcome is a comparison of Arm 1 ts Arm 3, with the airn of determining if the addition of
AZ is effective. Using the proportion of patients that are virus-fiee at I days as fre pinr,rry endpoint nf
the sludy, and assuming that the proportion of patients in *re hydroxychloroquineanfi who are virus
free at 6 days is a-571, the following table showsihe detiectable pioporrion ,irui+.* in it " 
cornbination
arm with S0% power. These samples sizes are wifr a SYo leveliwo-sided test of proportions.
For example, if we enroll 60 patients p€r irn, we could detect, with 80vo povrer, en increase in the
proportion of virus-fee patientsfrom 57.1% in the hydroxychloroquine arm to g0.S% in thecombination
arm.
The two-sided Type I enor probability associatied with this test is 0"05. tAte wig use an qnconecded chi-
squared statistic to evaluate this null hypothesis.
A semnd, independent goal of ttre study is to ensure that, in fact, hydroxychloroquine is effective in
reducing viral load. Thus, we plan a third, conbol arm, in which patients wiil receive s placabo for six
days, at whieh time lhey will switch to receiving HCQ. We plan to compare arms iaiia 3, wi& the
conbol (Arm 3) having half the sample siae of Arm !. Based on the Gauket et al. study, wE assums
the baseline proportion of patients who are virus-free at six days is 0.I2S. The followfnrg't"Ut" shows
the detectable difference with a variety of baseline rates:
Propcrlion virui-kee
HCQ onlv
Proportion virus-free
HCQ plus AZ
Proportion difference
Patients per rm
0.571
0.821
0.350
52
0.57{
0.805
0.l3tl
60
0.571
0"771
0.200
85
0.571
0.721
0.150
158
Proportion virus-fi'ee -
HCQ only
Proportion virusEe
HCQ plus AZ
Proportion difference
Palients pei rm
Pmtocol Versinn Date: 0&Mry-?0fr1
Page 12 ofl|8

Thus, for a range of plausible virus-free rates for the control arm, the detectahle rab for the l-tCQ arm
is wellwithin the range reported by Gautret et al. [9]" With this thrae-arm study, we will need 60 patientr
in each of the first twc arms and 30 in the confol arm, for 150 in total.
A key secondary endpoint will be the number of days *om initiation of therapy to
disease). Thia can he displayed graphically using Kaplan-Meier survival curves, and
l.S Etudy Variable*
A. hdependcnt Yariables, lnteryentions, or Predictor Variables
The followirg variables will be examined for treatment oulcomes of
outsmes:
r TrcatrnEfit
. 
Baseline temperature
o Baseline viral loads
. 
Baseline measuresof rytokines
r Baseline measure of inftammatory marlels
(virtually no
assessed
using a log-rank test. Otfrer secondary endpoints that can be assessed in this way are 'l) Time in days
to being afebrile far 48 hours, {2} time in days to resolution of symptoms (as
by a symptorn
questionnaire), (3) time in days to discharge {if hospitaliz*d}, and (4} time to reeovery
to refurn to
wsrk or schcol). Oher measurcs tretwlll be assessed via desoiptive stai*stics are
improvement over tlme in vital signs.
toxicity and
efficacy and/or predict
B. Dependent Variables or Outcome lileasureg
The following variables will bB examined for changed as result of treatrnent or as predictors
. Treatment Compliance
. 
Charge in the iever curve
r lmprwement in vital signs
r Time to discharge (ilhospitatiaed)
' 
ddverse Events (number/perc*ntage/grade)
" lnFatient versus Outpatient
. 
Mild b Moderate disease versus Severe disease
. 
Change hom haseline viral loads
' 
Change fom baseline inffammdory markers
{.7 DrugslDeviceslBiolcgics
Gensric neme: Aaithrnmyein
Commersial name: Zlhromax" Zrnax
For mmplete information please re&rto the package inserls at
htFs ://dailyrned 
" nlrn, n ih.gouldailymedlazittxBmycin
Psge 13 of{S
0"125
1
0 276
80
0.150
A 'it
0.280
60
0.200
0.497
0.290
60
0.250
0.554
0.304
60

cletllical name: {2R,3$,4R gl,sf,.IgR,11R 12s,1gs,14r}1&t(2,edideoxy-3-6-methyr-3-o,methyr-
l*:1*F,yfry:nosyt) oxyl-Z-ethyr-s,n,ro-trinyoroxy-3,!,(,r;6,lari+"pri.rr"nvrlii'-iii,l,a
tndeoxy-3-(dimethylamino)-$-O-xflo-hexopyranosy[oxy]-'!-oxa-6-azacyctoientadeian-t$-one
Aeithromycin Tablets USP eontain the aetive ingredient azithrornycin, USp, a macrolide antibacterial
drug, for oral administation. Aziftromycin" USP is derived nom iry*rromycin; rrowevii iioiners
chernically from ery{rromyein in that e methyl-subEtituted nitrogen lrtom ls lncorporated inh the
lacbne ring.
Source: Cornmersially available
Ctfil
"f
c38H72N2CI't2 M.W.74e
Azithromycin, USP, as he rnonohydra&, is a white crystalline powder with a molecular
fonnula of C38H72N2O1!*H2O and a molecular weig-ht of 767. Azithromycin Tablets USp
are supplbd for oral administration es tablets containing azi*rromycin monohydrate
equivalent to eittrer 250 rng or 500 mg azithromycln, Udp.
F4{qaqpk!ryetics: Follouing oral admini*tration of a singte 500 mg dose (two 250 mg tabteb}
tq l!-E]"d lrg*l*,y mate volunteers, the mean {$D} phinnacokinitic parameters wj;e
.AUc&72 =.a"!,f .2) mc.q.hrtmL;cmax= 0.s (0"2) rnc!/mL Tmax = 2.2 (0.9) trours. rwo
1$h.roqvcin!50 rng iablets are bioequivatent to-a siigle 800 rng tabtet.
Elimination: Plasma concenlations dazisrromycin foiiowing sirfiB S00 mg oral and lV
doses declined in a nofyphaslc pattem resultingin a mean a[parint plasmiclearanee of 6i0
mUmin and terminal elirnination half-life of 88 hr. The prolanl'ed tenninal half-life ir tf,oughito
u*".9u" to o$ensive uptake and subsequent release oiurug ilom tissues. Biliary excreti.i- of
azithrornycin, predominantly as unchanged drug, is a maloi route of elimination. Over the
coursecf a week, approximately 601o of the adminis{ered dose appears as unchanged drug in
urine. The mean cmax and AUC$-120 increased 6196 and 3s%,'respectively, ln;rbi**tr'
with.seveli.lfnal irnpairment {GFR < 10 mUmin} compared to sr,Sje{*s with normal renal
tunctian {GFR > 80 mUmin}.
Contraindications:
Page'14 of {8
ffi,J**
&*
t

hypersensitivity to aeithromycin, erythromycin, any macrolide ir ketolide drug.
{equtic Oysfunction: Aailhromycin tabhts are contraindicated in patien6 wi*r a history of
cholestatic jaundieelhepatic dysfunetion associated with prior use of aaithromycin-
UUarnings:
Hypers*nsitivity: seriaus,allergic reaciions, including angioedema, anaphylaxh, and
dermatologic reac{ions includingAcute Generalized Elanfhematous Fuslubsis (lCgp),
StevensJohnson syndrome,.and toxic epidermal necrolysis trave ueen reportedin patiilnts
9n qzithromycin therapy. Fatalilies have been reported.-Cases af nrug Reiction *iih -- -
Eosinophilia and $ystemic.Syr.nplom: (DRESS) liave also Ueen repodeO. tf an atbrtic
leaction occurs, the drug should be discontinued and appropriate tlerapy should be' 
-
institutied. Fhysicians should he aware that allergic symp'toms may rea$pearwhen
symptomatic therapy has been dlscontinued.
Hepatotoxicity: Ahnormalliverfunction, hepatitis, choiestatic jaundice, hepaticnecrosis. and
hepatic failure have been reported, some af whhh have resultid in death" bontact their
physician if vomiting or inikbilitywittr feeding omurc.
$T lrolongation: Prolon{ed cardiac repolarieation and eT interyal, imparting a risk of
developing cardiac anhythmia and torsades de pointes, have been seen with treatment with
maerolides, including azi&romycln" Cases of torsades de pointes have been spontaneouity
reported during post m3*g!ng surveillance in patients receiving azithromycin.'prcviders
should consider the risk gf QT prolonga$on wlrich can be fatsl itren weigfiing the risis anU
benefrts of a:ithromycin lor al-risk groups including:
r patients with known prolongadon of the QT interyal, a history of torsedes de pointes,
congenital long QT *yndrome. bradyanhythmia's or uncomfensated heart hiture
r patiefits on drugs known to prolong *re eT interval
r patientr with ongoing qroryhy$mic conditions such as unconected hypokalernia or
f,tVPolagnesemia, clinically significant bradycardia, and in patients releiving Class lA
{guinidine, procainamide) or Class lll {dofelilide, amiodarone, sotalol) antiaitryttrmic
agents.
Elderly patients may be more su$ceptible to dmg-asxociat*d effects on the eT interval.
Clostrldium dffiicltaAssociated Diarrhea {CDAD}: C}asindium dfrBfcfla-associated diarfiea
has been reported with rge of nearly all antibacteria'i agenb, including aaithlomycin, and may
range in sgyeri$ fiom mild dianhea to fatal colitis" frearnent with aniibacte*af iger;ts aiters
the normal flora of the colon, leading to overgrowth af C. diffieite.
Exacerbatio-n of Myasthenia Gravis: Exacerbation of symptoms of myasthenia gravis and
new onset of myasthenic syndrome have been reported in patients reciiving azidrornycin
therapy.
Develapment of Drug.Resistant Baeteria: Prescribing azithromycin in the absenee of a
proygn or strongly suspected bacterial in{ection is unlikely to provide benefit to the patient
and increases the risk of the development of drug-resislait blcteria.
Drug interactions: Nelflnavir, Warfarin.

Potential Drug0rug lnteraction with Macrolides: lnteractionswith digoxin, colchicine or
phenytoin have not been reported in clinicat triad tilh asthffitcin. rrr"-"i"iiin" aiiri"- -.
inleractiorl sfudies have bein performed to evaluate potenti"-r'oi'ig-d*g interaction. However,
drug interactions have been observed with other macrotid;il;;t. untilfurther data are
develoPed regarding drug inleractions when digoxin, corcrriiin* #fhenytoin are used wipr
azithromycin careful monitorfng of patients i* advised.
Availability.: FDA approved; conrmercially available azithromycin will be supplied *ee of
charge tro all patients enrolled.
Generic nalne: Hydroxvchloroquine sulfate
uommercaal name: plaquenil
For complete infornation prease refer to the package inserts at-
Chemical name: 7'chloru'4't4-tethyl-{2-hydrcxyethyl}arnino}-I-mefrgbutylarnino} 
quindone
$ourcs Comrnercially available
"llt 
H
\A_zN.,A.-A
t" il i*,Y T
* \,rl
c18H:6CtN30't-t2s04
" $3$*a
CX;
CIH
Molecular Weight 433.95
HydlolVchloroquine sulfatre tablets, USP contain 200 mg hydroxychloroquine sulfate,
equivalent to 155 mg base, and are for oral administrati6n."
Fh{.ma4inetics: Following.a single 200 mg oral dose of hydroxychloroquine sulfate to
healthy males, the mean peir nuoo concentiation of htdrdicrrroioquine ris reg.6'ng1111r,
reached in 3'36 hours wisr a half-life of 537 hours_{32.{dry"i. ln tt " 
same study. the plasma
peak concen8ation was 50.3 ng/rnl reaehed in 3"?4 noursivitn a irrnrife otzgff fiorrf,-- 
'
{123'5 9ayl), U.1ne hy{roxychloroquine levels were still detectable atur 3 months with
approximately 10% of &e dose excreted as the. parent arug. n;sulti rolro*ing " *infir uou*
of a 200 mg tablet versus LV. intusibn {155 mg), cemonstrliea i rtirruir" ot"lJ* aE urv"'
and a large volume of distribution.
Meclaniryn of Action: The precise mechanisrn by whichhydroxychloroquine exhibik activity
against Plasmodium is notknown" Hydroxychlorfuuine, rire crrriioquine, is a weak base and
may exert its etfqct by qfentrqtingin theacid-veiicles orure [aia]ite inu uy i-hi-bitd; -.
polymerization of herne. lt can alsolnhibit certain enzymes nv nt*o"tion with DNA.
Poge 16 of rl8

YYarnings:
Oculer: lnever3ible retinaldgmage has been observed in some patients who had received
lV{roxycryoroquine sulf-ate. Signtt*cant risk factors for ret}nal aamagi incrro" i"ifv-Jogr of
lVdroxfehloroquine sulfab greakr than 6.5 mg/kg {5 mg/kg nasejit actuaf oooy wEUfri
durations of u1e greater than five years, suun*mlt'gtorierilar filtration, use Ef some-
concomitant drug products such as tamoxifen citratJand coneunent mi*far Uiie"rl"
Cerdiec Ery"S, including Cardiomyapathy and QT pnrlongation: Post-rnarheting cases
grlfe+nryyiening and tukl cardiomyopafry hlve been ieportel with use of
hydroxycltlorqyine sulfate as well as with use of chloroquine. Hydruxychloroquine sulfate
proiongs the QT lnterval. Ven*icular anhythmies and toriEdes Uir poirites fravL Ueen
lengrted in patients taligg hydroxychloroquine sulfate {see OVER.DOSAGE}, Therefore,
hydroxycftloraquine suliate should not be administeredwitfr onE Orudt#llnve the
poientialto prolong the eT interval.
Woreening of psoriasis and pcrphyria
Proximat Myopathy and I'leuropathy
ileuropsychiatric errents, including suicidality
llypogfyc*mia: Hydroxychloroquine sulfate ha* been shown to cause Eevefe hypoglycernia
including lasl of eonsciousness that could be lifie threaiening in patients trea6U *tidr
withsut antidiabetic medications
General precautions: GEn*ral: Use wlttr caution in patients wi& gastrointestinal,
neurological, or blood disorders, and in those with a sensitivity io quinine.
HepaticlRenal Disease:.Anlirnalarial compounds should be used with caution in patients
with hepatic disease or alcoholism or in ccnjunction lvith known hapatotoxic drugd. *
reduction.in dosage may he netessary in patientrwith hepatic or renaldisease,ls wellas in
those taking medicines known to affeit these organs.
llematologic Effuctrllabor*tory Tests: Antimalarialcompounds should be ug€d with
puti9n in patients with hepatic disaase or alcshalism or in *onjunc{ion with tcntwn
hepatotoxic drugs. Periodic blood cell counts should be perfonireo if patients are tiven
prolonged therapy.
Hydroxychloroqqlne sulfate should be admlnistered with caution in patients having glucose-6-
phosphate dehydrogenase (G-6-pD) deficiency.
Oennatologic Effrcts:.Oermatologic reactions ta hydroxychlorsquine suliate rpay occur and,
therefiore, prope, care should be eiercised when it is administered to any prti"iiii"**iring t
drug with a significant tendency to produce dermatitis.
Drug lnleraclgn* {include}ut nor timited ro}: _Qi,sqIie, InAUlin_9;n$idigBlic d,{qgq" Druss
th* prololq or interual"and pther Sr{t"rvthmobenire d.rupsffi;Tn&n
1o low,el the pgnv$sivi ttrrilhatd,,Ati!
Antacids snd kao{in, Cirnetidine, Ampicillit!
PagelTof{8

AvailabiliU: FDA appnrved; commercially available hydroxychloroquine sulfate wilt be
supplied tee of charge to all patients enriiled.
9eneric name: Microcnntelline Cellulqse
Commercial name: Flaoebo---
Source: Comrnercially availabte
The placebo for tablet is fmnrulated fsr oral administration. Placebo tablets arE blue, film
coated tahletswi$r K20 debossed on one side tc rnatch he active formulation. Tablets will be
qrovided in polyvinyl chloride {PVC} / polyethylene {FE) polychtorotifluoroethytene (pCTFE}
film bllsiers with a paper-backed foil and a secondary wallei for diEtibution to'patients in -
dinicalbiak"
Compo*ition:
Rcmm'eil druitg prncc *ring"
Eitlur ftrri$ed trYanr fiJSP. Ep) or packaged turised $rrter ([JSp] may bt used dufira procesiuS
a.
b.
Opad$ II Blus caut*ittspolyviuyl clcr:hol {USP" FCC" Phf,ur, JfE}, ritflriuur dioxitls (U$p.
FCf" FhHnr"f), n*lqelrylene glycol [ruacrogolJ NF, FCC, plrErri" JnfFA, fp], i,ut" (ggp,
FCC' PhEur, Jp), FD&CBIut il} {irrdigo csnirin* alruninrun l*ke), FL}&C Bllre.#t ftiri-lliant hlue
FCF nlnruinun lake), n*d FD&c ycll*w #i (rnrrrnzine ahunir.nuri lnke)"
Componeut
Staudsrd
Strength {:0 rug)
Quartity prr
Lhlt (mg)
9{ (wlw)
Intrxgrnnrdrr
Microcrysfft lline Cellxlosc (Avicel pH l a)2)
NT
| 5J.2
9?.Orto
Cff$eanrxll$re Sixlirun (Ac-Di-$oli
NF- EP" JP
3.:00
?.oo9d
lvfagtesiuu Stearate {uuu Brr,Ire)
NT. EP
L600
1.009r
Totll
I60.0
l(Xloz'o
Top-*oat
Opadry II Blue
Profesred
,1.800
r:a. 3.Cto.ro
Ihritied !t'aref
u$p. tP
Nr"{,i
N,1A
hrified $taier (Packsged) b
tisp
F$,{.
NIA
* ca.. npprxinrarely; EF, Eru:o1.lc*n phnlititcopeint l\T, Nffi
rnnularl: JP,
DruglDevice Aceountabil ity and Siorage Methods
Foge 18 of 48

B. Treatrnent Compliance
The $udy medication will be given in accordane with the protocol and the inskuqtions of th.
treating investigator.. F.or those subjects who are teatad ai an outpatie.t, ttt* st,iAy drugs will be
proy$ed to petientsb be self-administered. Patients witt be asred to uring nerimainin! tnal
medication to each -visitfora complianee check. The remaining tablets wif re m,unteo U! pre
investigatorlsib staff and recorded at ihe investigalor eih. Di*irepancies Uitryeep $e numberof
tablets remaining and the calculated numberof i;b{ets the patients strouu rt"r* tal*n must be
docurnented and explained. A pilldiary will be provided anb must ue comeriro $y-r,* pxleni r
document keatnent couse.
{.8 $pecimen Collection
A. Primarv Specimen Collection
The research samples collected will be studied using standard labomtory assays for:
l. Viralload
2. Meesurements of inflamrnatory cybkines in blood such as lL-8, lL-8, ll-l, TNF, INF ueing
standard ELISA protocols.
3. $erobgy.for Pfllence of antihodies to SAR*-CoV-2 and appropriate conpols, mea*r*ring
lgG and lgM. We willalso assess for general antigens "piiin" 
ror iAR$c;V-r:;;;I
as neutralizing epitopes.
. Typqs of Specimens:
' 
Pedpheral blood for whole blood, plasmar serum and buffo coat will be mllected at
baseline. day 3 or 4 and day 6.
. 
oropharynx Ewabs r,uilr b€ cortrected at basefine, day 3 or 4 and day 6.
r Saliva will be collected al baseline, day I or4 and day6.
' @g 
The specimens will be d*'identified by ttre CINJ Biolepositrory and assigned a
Patient lD, specimen lD, and dste of colleetion" Assijned lD'swillonly'ue ablti to beassiciatea
with patient.$ata hy approved users in the On0ore& clinical trial tricking sy$tem. No olher
identifiers will accanrpany the specirnens to their respedive analysis laboiatories.
samples will be transported to the BR$ by trained personnel. Following
!!ood and*amples will be stored until shipped by BRS in patches to the RUCDfr
Biologics, 145 Bevier Road, Piscataway, NJ 0gBS4.
PlPc?ssinu; Please rehr to lhe Conelative Lab manual for sample eoltection, labeling, and
shipping instructions.
$Ioraqe: All samples will be processed by BRS and transported to RUCBR fur analysis and
storage.
gi$Sg$!!iot!: Analy*is will occur at the end of the stuSlaccrual period. Specimens wil be
banked lor future use as part of llre analysis process for future conelaiive ituCies related to
this project. Please review to Protocol section ?.0 Research Repository.
B. Secondarv Specirnen Collection
N/A
1.9 Oata Gollection
A. Primarv Oata Collection

Elec{ronic case report forms {eCRFs} have heen designed to colled the data points ou{ined in
section 1"3 {D}. Compldion of the eleqtronic CRFs (eCRFs} will be done in ainordance with the
instructions in a study specific data capture plan. All eCRFs will be oomplete by the research
slaff of the Office of *uman ResaErch'serylces (OHRS) at the Cancer tnstitute of d;;l;y.
The eCRFs will be maintained in a csnfidential format in S're On0ore@ database.
B. $econdary Oata Gollection
NIA
1. { 0 Timetablelschedule of Errents
Please refer to Appendix A. All shrdy procedures will be performed eccordirq to the schedule or"*lind in
the Study Flow Table
Itfi 
lillirirrl[. l]llffi
!.1 Research Staff and Qualifications
2.2 Resoarch Staff Training
AII researclr team members will mmplete the requind Human Suliect Protection training trrough Sre
Gollaborative lnstiftrtional Training hjtiative {ClTi) Program prior to being approved to ta[e partin
this study. All study will attend the site iniliation visit for training abqut the study specific protocol.
The Principal lnvestigator will provide oversight ard ensure lhat the shrdy is conducted aecording to
the investigational plan and applicable regulations in accordance wi*r 21 CFR 312.
3.3 Resourcee Arraiteble
,Aeithrornycin and trydrorychloroquine sulfate will be provided at no charge bthe study participants"
I.4 Research Site*
The Statewide Research Office oversees multi-eenter sludies. ACiiviiion me*injs are siluaied piil;
activation of each study. These meetings are conducted on-site via Webinar to review the protocol with
the local Principal lnvestigator ancllor his/her research staff. lnformation reviewed includes lhe pnrcedures
for centralized patient registration, completion ol the electronic case report forms, data submission
expectations, adverse event reporting requirements, and any other study-specific issues. lf investigational
drugs are provided, then proper drug accountabili$ procedures are reviewed with the pharmacist.
3.0 Multi.Center

clinical research administration and coordinatian to assistwith IRB compliance, patient enrcllmenl data
collectian, and toxicig reporting for the sites throuEh OnCoree.
The Qualfu Assurance and Data Monitoring Offce of the OHRS is responsible for monitoring visits and
audits of data at ihe system sites. Monitoring is based on level of risk tut occur at a minimum of an
annual basis or after enrollment of the fimt tuo patients, The monibring vistt* and audits occur with the
purpo$e of veri$ing that documentation in tre medical and research records support data recorded in the
electronic case report forms located in oncoreo. Adherence to the protocol eligibility, treatment plan,
response and toxicity evaluation, and SAE reporting sriteria are reviewed. The appropriate documentation
of informed consent and documentation of administration of protocol therapy for ali enrolled patients are
reviewed.
Allmanitoring visit and audit findings are reviewed with th* research staff and pl. Unacceptable
manitoring visit findings are immediately communicaled to HROC. Allwritten reports are prcsentred to the
HROC aM subsequently to the lRB.
4.{ Subiect $election and Enrollment Considerations
A. Method to ldentify Potential $ubiects
An IRB approved press releasewill be distibuted to RuQers physicians trrough tfre Rutgers
Communications-Office. The press release will include a tetefhdne numberfoipotuntidltudy
particlpants to call. The potenlial study participant* wtll bE indmcted to virit the'shrg sit* cblrert
to their home.
Potential study participants will also be identified by the treating physlcian-investigabr torn new
patient refenals.
Both locations have identified a segregaled location to screen potential sugects for the trial.
$creening at both locations will be conducted by to be named Advanced prlafue Nurse and
Research Nurse. All research personnelwillwear appropdale PPE as au$ined
B. Recruitrnent Details
The sublects will be adults age 18 years and older with a diaEnosis of COVID-l9 and a confirmed
positive testfor S,{R$-CoV-! my any aeeepted me{rad. Potential strdy participants will be
recruited by the treating physician*investigator and approached for stur.iy-participation during
consultation for treatment and management of their disease. The discuisicn wilt take place-ln a
private room. The patient will also meetwith the research tieam to reyiew each page oithe
informed cansent documenf
fhis study Ull be avallablE to all patients who meet the eligibility criterta" There will be no
limitation to access with regards to race or gender. PatienG will be required to sign an IRB-
approved informed consentform priortn cornmencing eny research related ac$&"
C. Subject Screening
Fatients that lack decision+naking capacity will not be approached to participate in this study. The
feating investigator ard researsh team will interview the patient and rivkw the chert to
Fage21 of{8

determine if the patient is a potentialcandidah forthe study. Screening tesb to contirm wtrether
subjects are eligible for inclusbn in this strdy will be conducted including SARS-CoV-! test if not
already confirrned to be positive. The Principal lnvestigator, or designee, will be responsible isr
reviewing and confirming subject eligibility prior to enrollrnent to the study.
Suhjeck who da not meet all inclusion criteria will be recorded as screen failures in OnCore6.
' 
lnclusion Criteria
1. Patients with proven SAR$-CoV-I infeclion by an accepted assay with sympbrns
consistent with COVID-I $
Ablllty te measure and quanti$ viral bad by quantitative PCR
Age 18 to 89
Abilityto swallow oral medicafCIns
Falients must read, understand and sign IRB approved informed consent
. Exclusion Crihria
1. Fregnancy orwanren who are breastfeed*ng
2. Turo oonseculilrc negative alrsays for SARS4oV-2 infecticn
3. Fatistts that lack deeision-mEking capaci$ will not be approached to partlcipate in tris
shJry
4. lnability ts tclerate oralmedications
5. Allergry or prior edverse rcaclion to either azithromycin or hydroxychloroquire sulfrh
0. QTc inbrval > 470 Msec
7. Condilions potenlially resulting in drupinduced prolongation of Sre QTc intervals:
a- Gonganital or acquired long QTc syndroma
b. Family history of sudden death
c. Hirtary of pevious drug-indr.$ed QTc prolongation
d. Cunent use of medicalions wfth possihly sr kno\tr rtsk of QTc prolongation (see
6ppendi,{ B Srugs associated with a knomr or possible rbk of QTc pralongntion}
8. Hisbry cf ongroing vmtiorlar cardiac dysrhythmias of grade 2 as described by N$ CTCAE
5.0 criteria
g. Histcry of serisrs venlricular anhghmia (W or VF > 3 beats in a row)
4,l Sesondary Subieets
NIA
4.3 Humber ol Subiec{r
!rt/A-
C. Feasibility
Given tlp curent incident rate" ir snt$cipated that enrollment will be com$eted within 3&40 days.
4.4 Gonsent Prccedures
e
3.
4.
5.
B.
A.

A. ConsentFroeesc
Provision of wrifien sr verbal lnformed consent will be obtained pricr to any study-related
procedures' The lnvestlgatorwill en$ure tr'aittle ituov-pirric,pailt ir giu;n tuti#u i&rr* oral
and written intormarion a-bor.rt the nalyre purpose, possibn,,*'k 
"na til;&,Ii# ,ilt. study
participants will also be notified that they are tree id cir.onrinu"irorn rhe study at any time. The
study participantwill begiven the opporiunry.to aii d;;iffi;;d arowed rime to considerthe
information provided. The original,;igd u,,ritten rnninnJcoisent Form w$t be given tro fie
study participant.
cunent FDA, oHRp, NlH, state and institutional regulalions conceming informed consent will be
followedr An IRB approved written intorneo crns*ni dilm;i fiat embodies the etements of
informed consent is required 45CFR46.116
1' The investigator shall explain participation.is votuntary and all aspects of the :*udy purpose
of the study, trearment plan, prncedirgl, 1is!s, r*n*i*, iGnatives, and the rightto refuse
and withdraw at any tirne wittrgul penany in rey ranguiil - '
? The investigaror wiri.a-n:we.l afl thi pati*t'. d,"rii,;n, TJgaraing rhe study.
3' The investigator shall qiyg th9 patleni aueq"rii" opport nfiV L reac ihe consent fonn and to
discuss with farnily anO ffends,
4' lf the patient decidesto particlpate in the study, he/she wilt be astced to sign the lnformed
consent Document. A copy of'the signed lnrairirea a;";;iDo"urnent will be given to the
patient and this wilr be documented i-n me patieni" *.Jl*i**rc.
4'1 Patients who are unable to read ilr*'mnreni l, i*piriilr wihess who is independent of
the trial will afiend the inbrmed consent process aird reaos the informed eonsent and
other wriften infonnation.supplied to the iaaidt" iiie impa*lat witn$;;[i,gi n*
infsnned cunsent form. A ciiy of the slgh&-rnid;'ionsent ooqmeni wiiihe given
to the suhiect and-this proceii willbE aicu*enno in G pauenrs medical record.
5" The investigatoishait *1"* ;i[d;;i- $3rr-r"J m" i6r,ito ,*n *e study parriciparion and
wi&draw ttrair participation at any time withJut n*nrrty ,iJ*in be treated lvithout prejudice.
. Location ofConsent process
The consent form will be reviewed by *m investigaiDr, or a delegated study member, in the
clinic or hospital roryn. pldy parti*fiant must sfin ttie sonsent inpersan at ttre participating
institution. lf the patient wisirds tc enrroll nn the -[rav, trl 
"r rt e will sign the infomred
consent in the presence sf a physician or nurse on tle s&dy-team.
' 
Ongoing Consent
lf there aI? any "I"F"t [!he Rrotocol, these changes will have to be first reviewed and
approved by the Rutgers IRB via an am.endment oerire iny'*rrrng* is implemented. once
approved, study participants will he noti{le-d otttre proiocoi'i,tr-"*gru and will be provided with
the updated infor.me! consent form (lcFlforthd-{E;;i;;;'ilnu"***ry. Stus participanrs
will also.he provided with a copy ortire upoated lcFitt}reir records whenever re,consent is
required.
' 
lndividual Rores for Researchers tnvorved in consent
only a treating investigatror or researsh nurse lisied wittrin the IRB applicatian will consent
study participants & this study.
Cons*nt [iscusrion Duration
It is anticipahd that the informed consent process will take 30-g0 minutes.
Coercion or Undue lnfluence

This sfudy requiresstudy participants to. provide &nsent" Adults unable to cansent or
cosnilivetv impair3.d adutrs wiil nor ue.ell$ian f* ff ir;ldy: 'ffiffiffi Ir,fi*.n and/or
research nurse will explain to the sludy 6y&ipant *rJp-aitolpa*on in frd'iidil?I Sffi",,
voluntary and the srrdy pariicipant cari;itil;;;t;i ti*r.
. lgbiectUnderstanding
The lreating invesiigators will eeek consent cnly under circumstances fiat proylde the
prospective. stttdy p-a$c{pant the apporhrniry to'oniuer whether t" particilffi ard that
minimizes the pmsibili$ of coercisrior unaue innuen.*._rn" information given to flre palient
lllill k in a language understandablq q tne patie*i."5um**nt tirne wil be agourcd for
questlons !o be as(ed and ansrvered, both 6t ilr* p"tl*t and the inuiyiarrat obd;iril consent
to ensure the patient mmprehends ttilcon#ni il,E#il**" - -'y " r-"'esq'. w
8. Ullaiver or Alteration of Consent process
N/A
C. Documentalion of Consent
. Documenting Consent
Written informed consent.is required. lntanned cnnsent n*ust be obtained nrior b
co".fT9$Ig31Uese3rch procedures" lniormEd consent *itI b;;;;;niJ;,I""*ro"n*"
t#itr z1cFRso.3r; il shail bi documenred by tu* Lr* *, ;fut", ;ir-slffiffi *;ffiff"
the trRB and signed e$ Ptgd by $re stuoy iartlcipani"i rtrr ti*" or il;;;i.'; copy shag be
given to &e person signing ttre iorm.
' 
$Xiver 
of Documentation Of Consent {i,e., will not obtain subiect,s signature}
4.5 Special Consenffpopulations
A. tlinors€ubiects Who Are llot yet Adults
t{lA
B. UUards of the $tate
IUA
C. llon-Engtish-$peaking Subjects
Eoth rnen and women ina mlmoers of all efrnic groups are eligible for *ris bial. No special
recruitrent wiil be performed based on gender or-minluity st"tus
where infonned csnsgnt is doeumented in sccordanse with 46 cFR117 (b) {1}, the urritten
ennsent document =9*!u embody, in lanquage unoerstanciable to ffle stltv p',irii*lpanl al the
elementc neessaryfor regaily efiLuive in"ionieu ccn;;:*'
' 
Process for Non-English€peaking $ubiects
1' An IRB approved short f6rm wrifen uosument shall be presenbd in a language
underctandable to the study participant-
?' The IRB approyea lplstr inrumel eonsent document may serue as a summary.
3' An interpreter fiuent in engush "$ qp p"d;i; ild;age shar present rhe Enstish InB
eonsent form.offered, read it and orally present ittoihe-patient.
4' Through the interpreter, the investio3l*-,iti"-rnliin earticipafion is voluntary and all
aspeck of the sludy' the purpose of the study, treatiient plan, proce&rrss, risks,
Page 24 of 48

benefik, altematives, and tha rightto refuse and withdraw at any time without penatg in
lay language"
5. Through the interprebr, the investlgator will *ns!i/€r eny questions Sre palient may have.
6. The lnvestisator s!{l g}ve lhe stud} participant aoqu*e';#ffiity d#; d;r'Ril'-'
approved English informed conseni document home tor reriil t d;it6;loiri"nu*
who are fluelt in.English and the language undemtandable to the patierit.
7. lf the patienl decides to participate in ttrJstudy, he/she wilt be asked to sign the short
form document
8. The lRHappnrved informed consent documenl will be signed by the per$on obtaining
consenl for authorized under the protocol.
9. The witten short form document and the English infiormed consent document will be
signed by the witneas.
10" When the percon obtaining conEent iE aseisted by a translator, *te lranslator may serve
as a witne$s.
11' A copyaf.*re signed IRB approved short fum document and the English informed
conselt document will be given tio the study participant and this will be documented in the
patienfs medieal record.
12. Through. the interprehr, the investigator shall inform all patients they have the right to
retuse $uAy qarfigipation and witMraw their participation at *ny tirnl without peirary anU
will be feaEd without prejudice.
. $hort Fonn Consent for f{on-English Speakers
Study participants who do not speak English will be presented with a short fonn emsent
docurnent witten $n a language undemtandable to them.
D. Adults Unable to Consentl Decisionally lrnpaired Adults
Patients that lack decision-making capac$ wifl not be approached to participate in this study.
N/A
4.6 Economic Burd*n andlor Compenration for $ugeetr
B.
G. trompensation Documentation
ll/A
4.7 Risks of Harm/Potentialfor Benefits to $ugects
A. Description of Risks of Harm to Subjects
. Reasonably Foreseeable Risks of Harm
Azithromvcin Adyerse Errent*:
Study participants will not reeeive eompensation for participation.

is uesc'roeo il ffiffifilffifi#::ffiil]ffi?,ffi the nve (5] dosing
planned,
&rrgc
Raglman
Dlenhca 96
Abdomlnrl Prln g6
Vomltlnt ?6
Naueca
%
Rcsh
v,
$day
1.8%
1.7*A
1.1%
0.5%
0.4o,&
Bomgc
Ragimcn
Dtrrrhea/loosr stool* %
Abdornlnal Prin g6
Vomitlng96
Naucca
,6
Rreh
%
5day
5.8%
1.9%
1.9%
1.9%
1.696
Dosagr
Rcgirnen
Oirrrhaa }l
Abdsmlnal Paln 9(
Vomlting %
Nrusca
?6
Raeh
,(
5-day
5.4%
3.49d
5.69o
1.896
4.7%
The incidence from three different regimens all based
r Cardiovascular: palpitations, chest pain.
Gestrointeslinsr: Dysprpsia, flatursnm" vornfiing, mer€na, and cftoresi.rcprnaioe.
G*nitcurinarf MoniliE, yaglnttiq and nepkilis"
t{enrous Syxtem: DEzineaq headsrfta, v6rtigo, and sernnolencB.
General: Faligue.
ANlergi* Ra*h, prur*hr, phobsensltivity, and Erryioedema.
' 
Laboratory Abnormalities: c-linically significant abnormalities (inespec,tive of drug
relationship) occuning during the ctin'icitiriais were reported as follows: witr an incidence
of greaterthan 1%: disreasid rremoglobir,, r,**rtoi*[lli"itoyt*", neutrophits, and
Page 20 o{l|t

blood glutose;elevet*d seruffi creatinina phosphokinase, potessium, ALT, GGT, AST,
E}UN, creatinine, blood glucose, platelet counl, Iynrphocytes, neulrophils, and eoslnophils;
wi& an incidence dless thnn 1%: leukopenia, neutropenia, decreased sodium,
potassium, platelet count, elevated monocyles, basophils, bicarbonate, sen m alkaline
phosphatase, bilirubin, LDH, and phosphate. Most subjects with elevated serum
creatinine also had abnormal values at baseline. When follaw-up was provided, changes
in laboralory tests appeared to he reyersible.
tlydrorynhloro[uine $ulfate Adyerse Events:
The package labeling does not provide ar clear a percent incidence as modem labels since
hydroxychloroquine is an old medication. The following Councilfor lnlemational
Organiaations cf Medical Sciences {CIOMS) tequency rating is used, when applicabl*: Very
coxrnon > 10 %; Common I 1 and <10 %; Uncomrnon e 0.1 and < 1 ,h; Rare:0.01 and
<0.1 %; Very rar* < 0.01 o/o; Not known (frequlency eannol be estimated frorn available data)"
. Blood and lyrnphatic system disorders
Nolknorn: Bone manow depression, anemia, aplastic anemia, agranuloc$osis,
leucopenia, and thrombocytcpenia (see Wamings and Precautions, Hematologic),
" Cardiec disorders
Nol l<npwn: Cardiomyopafty, wtrich may result in cardiac failure and in some ceses a
fatal outcome. Chronic toxicity should be considerad when condudion disorders {bundle
branch blccU atrioventricuNar heart blrck) as well as biventricular hypertrophy are found"
Drug discontinuation may lead to recovery (see Wamings and Preeautions,
Cardiovascular, Drug lnteractions, and $ymptoms and Treatnent of Over dosage).
Hydroxychloroquine prolongs the QT, PR and/or QRS inlervals which may lead to an
anhythmia. Venbicular anhythmias and torsade de pointes have been reported in
patients taking hydroxychhroquine {see Wamings and Precautions, CardiovaEcular, Drug
lnteractions, and Symptoms and Treatment of Over dosage)"
r Ear and labyrinth disorders
Uncommon; t 0.1 and < 1%: Vertigo, tinnitus.
Nof lrnown: Hearing loss, including ca$es of ineversible hearing loss.
. 
Eye disorders
Cornrnon: r t and <10 %: Blurring of vision due to a distu$ance of accomrfiodation
which is dose dependent and reversible {see WARNINGS AND FRESAUTIONS,
OFhthalmslogic).
Unwmrnon: e 0.1 and < 1 06; Maculopathiex, which may be inever*ible. Retinopathywith
changes in pigmentation and visualfield defects {see Wamings and Precautions,
Ophthalmologic). ln its early form it appears reversible upon discontinuation of the drug. If
allowed to develop however, there may be a risk of progression even afier treatment
withdrawal. Patients with retinal changes may be asymptomatic initially, or may have
smtomatous vision wifi paracentral, perteentral ring $pes" ternporal scotomas, abnormal
color visions, reduction in visual acuity, night blindness, difficulty reading and skipping
words. Cornealchange* including edema and opacilies. They are eithsr symptornlesr or
rnay cau$e dislurbances such as halos around llghts erpecially at nigh[ bluning of vision,

vlslofi disrurban*s, or pholophobia" They may be bansient or are rev*sibre rryon
dismnt*nua^tion of therapv {see warningsana brecart*i, op},tharmorogic}.
Nolfronm; MacularAegeneration, v&i&l *ry nr A***tf"
. Gastroinlestinaldisorders
Varv cornn!.an: z l0 %:Abdominal pain, nausea.
Oom mon: Dianhea, vomiting.
ffiffifrns 
usually reiotue immediatiely upon reducing the dose or upon stopp*q
r Hepatobiliarydixorder*
{lnmrnrnon: * 0.1 and < 1 %: Abnormar river funcrion teets.
Not known: Furminant hepatic fairure (see wamings aM precautions,
Hepatic/Biliarylpanereatic). '
r Imrnune system disordem
Nol j*nown: Urticaria, angiedema, bronc,frospasm.
r iitetebolism and nutrition dissrders
cammon: a f and <!0Yo:Anorexia (usuelly resolves immediately upon reducing sre
dose or upon stopping the teatment).
Nof lcnpu*'rn*yly:.rjr: yurl,tgr and precautions, Endocrineand Mehborism).
t'tvdrory.chroroquine may exaoerbab drphyria i;; d;id;; i;;il;Ew"r'|,
General).
. Musculoskeletal and connective tissue dicordss
Unwrnmon: l 0.1 and < 1 oloi Sensori motor disorders.
Noflnonrn: skeretd musde parsim or skeretar ***. *yopathy or neuronryrpatfry
leadirE t'o progressive weakness and atophy or proximaimuscle groups. Depression of
tendon reffexes' abnormal resulls of nerve "i"o,i*". r"rr. frvopatrry may be rcveruible
after drug discontinuation, but rccovery may rake **v *ontr,; iG h;id; ;-J' -'
Frecautions, Musculoskeletal).
r Hervous system disords:n
6anr*on: > I and <lA 16: Headache.
Uncprnmon: Dizziness.
Not knawn: convulsions. Exkapyramidar reac-tions sueh as: akathisia, dystonia,
dyskinesia, gait disfinbance, trimor.
r Fsychiatricdisordels
Conynon- a f snd <10 ?6:Afied lability.
Uncurnmon".E 0.1 and < 1 %: Nervmxness"
IVof *nonra: Psyehosis, suicidsl behavior.
r $kin and subcutanaous tissue disorders
Pelp 2l of{8

Gomman:a., and <t0?a: Skin rash, pruritus.
Uncornmon: e 0.1 and < 1 %r Figmentary changes in skin and mucous nembranes,
bleaehing of tuir, alopecia. These urually resolve readily upon ceosation of therapy.
fr/ol*norn: Bullous eruptionr {including urticarial, rnorbilliform, liehenoid, maculopapular,
purpuric, erythema annulare centrifugum), toxic epidermalnecrolysis, erythema
mullihrme, Stevens.rahnson syndrome, Drug Rash witr Eosinophilia an$ Systemic
Symptoms {DreEs syndrome}, photosensitivity, exfoliative dennatitis, acu{e generalized
exanthernatous pushlosis (ACEP) (see Wamings and Precaulions, Skin).
. 
Risk of Harm from an lntervention on a Subject with an Existing Conditipn
N/A
. Other Fore*eeable Rieks of llarm
One potential risk is loss of confidentiality. We have taken several steps to rninirnize ihe
prohahility of this risk-
. Observati*n and $ensitiye lnforrnation
N/A
B. Frocedures which Risk Harm to Embryo, Fetus, andlor Pregnant Subiects
Women who are pregnanl ar unwilling to stop breast feeding are excluded from thtis trial due b
the absence of data which demonstrates that this tfrerapy changes morbidity ar mbrtality"
The U$ FOA labelling torhydroxychlorcquine riEk states the following:
Teratoqenic Effects; Human pregnancies resulting in live births have been reporEd in the
literature and no increase in the rate of bir*r defec$ has been demonstrated. Embryonic deeths
and malfomrations of anophtralmia and mierophlhalmia in the offspring have beenr reported when
pregnant rats received large doses of chloroquine.
Nursing Mo&ers: Cautlon should be exercised when administering PLAQUENIL to nursing
womEn. lt has been demonstated that hydrorychloroquine administered to nursing wornen is
excreted in human milk and it is knoum that inhnts are extremely sensitive to the bxic effeds of
4-aminoquinolines."
All patients rnust be nrade fully aware of Sre information relating tc the potential for reproductive
toxiciiy as detailed in the lnbrm*d Gonsent Form. Patienh of childbaaring potential and treir
partterc, who are sexually ac,{ive, must agree b the use of lro highly effedive forms of
contraceplion throughout their participaton in the shrdy and for 4 weeks affer last flcse of study
drug(s).
Women of childbeadns pqtential
Females of childbearing potential should use reliable methods of contraceptbn *om the time of
screening until 4 weelts affer disconlinuing study tresknent. Acceptable methods df confaception
include abstinence, tubal ligation, combined oral, tansdermal or inlra-vaginal hormonal
contraceptives, medroxyprogesterone injections (e.g., Depo'Provera), eopper-banded inta-
uterine devices, hormone impregnated intra-trterine systeme and vasectomised p4rtners. All
rnethods of conlraceptlon (except fior total abstlnence) should be used in combinalion with lhe
use of a condom by their male sexual partner for intercourse.
Males

!-

r proteding pHl agalnstpublic viewing;
r Proper storage and disposar of documents that contain pHr;
' 
safeguarding computerwo*stations and dstabases that aecess pHr.
F. Potential Benefits to Subjects
There rnay be direct b:n*!t to ttre palient for participation in this study because tre s6y
parliclpant will receive hydroxychloroqulne sutrate *rh otwid;;i;id-,";rdilwr[icfr?]e rn*
approved and have been sho,vn to have ro.lentlal.gtiriry an'prGnts with covlD-lg, althouglr this
does not guerantee that each inuividuir iatient wifi u"ndni"' ----
CIata gathered h*$i* lpdr mav atlow uslo ioentiry an effective treaknent fior covlD-Ig that
could result rn beneFn to the iatient or society 
"u *h*e in uru trr.u.
5. { Health lnsurance portabirity and Accountabirity Act {r*rpAA}
It is necessary lhat Pt'il be r**ssed- tr aqplrf u{*gd"}ihi* sr,rdy" Ag researeh p$,*onner ar.
fralned in HIpAA ard routine protections qf pHi *ill ;ppfi.-" "'
The lnformed consent Form-will inmrporate.wording- thet corngies wi& relevant data pirotection end
PlvacY legislation. ln accordance witrr nn Fleallh rrr""fi""'bortability and AccounhhilityAct
{HIPAA}' the writbn lnformed consent Form rnusl ncruJe a suuiect *uthoriaation tra relgase rnedical
in&nnation to a regulatory auihority, or lnstitutioniiC;;ild;rd (lRB), to grant "*-S]i][#ffi
medical infurmation that includes ailhospitatrecords retevEnt L the study, induding supjec,*, medical
history.
The corc elemenb *ncluded in the HIpAA authorization are:
' Ifff:|jf,ffi1*;ffi*"* 
ro ue uieJ o, al-J"*Jtr'at $denh'fies *re infurnariqn in a srecifis
' 
The name or other speeific identification of the person{s}, or crass of persons, autherfaed to make
the reqtlested use oi disclosure; 
v' vrs" vr 
"Er-..lit' 
inutr
' 
The name or other *pecific identificatiol of the person(s), or class of persons, to whpm the
pyerq e!ftty Tav rnake the rcquested ,r* o, cir*orffia' -'-- v' rb''vr''' s w
' 
A desuiption of aacft purpose of the requesM ur. oi oiilouur.;
' *mln 
date or an expiration 
"u"ni 
ttratreraies tolrrJinoiviouat or the purpose of the use or
. 
Srgnature of the indivldual and dah.
5.3 Farnily Educationat Rights and Frivacy Act {FERpA}
N/A
5-3 code of Federar Regurarions Tiile 45 part 40 {vurnerabre popurations}
5.{ Beneral Batr protection Regul*tion (6DpR}
t{/A
5,5 iIJ Accesr to Medical Research Act {Surrogate Corcent}
N'A
Poge 31 of ,18
5.0 Special Considerations