Conditions: SARS-CoV-2 COVID-19
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 75
Healthy volunteers: no

Brief summary:
This is a three-arm randomized trial comparing the efficacy of single agent hydroxychloroquine to the combination of hydroxychloroquine and azithromycin, and to a delayed hydroxychloroquine regimen, which will serve as a contemporaneous Day 1-6 supportive care control, in eliminating detectable SARS-CoV-2 on day 6 following the initiation of treatment in order to determine which regimen is more effective.

Detailed description:
PRIMARY OBJECTIVE:

I. Determine change in viral load at day 6 compared to baseline between two regimens to treat COVID-19 and a contemporaneous control group.

SECONDARY OBJECTIVES:

I. Time to resolution of symptoms (symptom questionnaire)

II. Change in the fever curve resulting in shorter time to afebrile for 48 hours

III. Normalization of vital signs

IV. Time to discharge (if hospitalized)

V. Assessment of agent toxicity as measured by standard metrics

VI. Collection of throat swab and blood for viral load, presence of IgM or IgG antibodies

VII. If feasible on samples collected for quantitative PCR decrease in virus shedding (in oropharyngeal secretions)

VIII. Measures of cytokines in blood including IL6, IL-8, TNF, INF

IX. Routine standard of care labs obtained as part of the care of these patients such as differential white count, CRP, troponin and LFTs will be analyzed for correlative trends

Arms:
arm 1: * Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days
* Azithromycin 500 mg taken by mouth on Day 1, followed by
* Azithromycin 250 mg taken by mouth once (1) time a day for four (4) days. arm 2: • Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days arm 3: * Placebo pills Days 1-6.
* If you still have COVID-19 symptoms you will receive Hydroxychloroquine sulfate 200 mg by mouth three (3) times a day for 10 days

Interventions: intervention 1: Hydroxychloroquine Sulfate + Azithromycin intervention 2: Hydroxychloroquine Sulfate
Intervention descriptions: intervention 1: Given PO intervention 2: Given PO

Protocol document:
ICF_002.pdf: 
OfficialTitle:
Randomized Comparison of Combination lrithrory.in
and Hydroxychloroquine vs. Hydroxychloroquine Alone for
the Treatment of Confirmed COVID-19
NCT number:
04336332
Document Type:
Consent-Main
Date of the
Document:
04/2U2O2O


TITLE:
PROTOCOL NO.:
PRINICIPAL
INVESTIGATOR:
Randomized Comparison of Combination
Azithromycin and Hydroxychloroquine vs.
Hydroxychloroquine Alone for the Treatment of Confirmed
covtD-19
STUDY TITES
STUDY SUMMARY: This consent form is part of an informed consent process for a research
study and it will provide information that will help you decide whether you want to take part in this
study. lt is your choice to take part or not.
The purpose of the research is to determine if azithromycin combined with hydroxychloroquine is
better than hydroxychloroquine alone for treating patients with symptoms consistent with COVID-
19. Azithromycin is approved by the Food and Drug Administration (FDA) for the treatment of
infections. Hydroxychloroquine is approved by the FDA for the treatment of malaria and auto-
immune diseases (lupus, rheumatoid arthritis). The use of hydroxychloroquine and the
combination of azithromycin and hydroxychloroquine is experirnental and has not been approved
by FDA for the treatment of COVID-19. lf you take part in this research
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ffi,e?lApRIL2o?o


to take part in the study. lf you are eligible to take
undergo laboratory tests, and study procedures at specific time points during the study. After you
complete the study treatment, you will have end of study laboratory and medical tests.
As part of this study, you will receive one of the following treatments: 1) Azithromycin and
Hydroxychloroquine; 2) Hydroxychloroquine alone; or 3f placebo pill foi 6 days foilowed by
Hydroxychloroquine. Treatment will continue for 10 days.
Possible harms or burdens of taking part in the study may have side effects from the study
treatment such as nausea, vomiting, dianhea, stomach pain or inegutar or stow heart rate. you
may feel discomiort and/or pain during some of the tests or procedures in the study. your
condition may not improve and could even worsen if you take part in this study. Possible benefits
of taking part may be improvement in your condition. lnformation learned from the study may help
other people in the future. However, it is possible that you will not receive any direct peisonat
benefit fom taking part in this study.
Your altemative to taking part in the research study is not to take part in it and pursue other
available treatment options as described above afier talking with your physician.
The information in this consent form will provide more details about the research study and what
will be asked of you if you choose to take part in it. lf you have any questions now or during the
study, if you choose to take part, you should feel free to ask them and should expect to be given
answers you completely understand. After all of your questions have been answered and you
wish to take part in the research study, you willbe asked to sign this consent form. you are not
giving up any of your legal rights by agreeing to take part in lhis research or by signing this
consent forrn.
!t,HO IS CONDUCTING THIS STUOY?
nthePnncipallnvestigatorofthisresearchstudy.APrincipallnvestigator
nas the overall responsibility for the conduct of the research. However, ofien other individuils
are part of the research team.
I 
lnvestigator or another member of the study team will also be asked to sign this
,nformed consent. You will be given a copy of the signed consent form to keep.
GJlf,:#?L3ilNi,3-?JiT,".,",pi,"iory i*ness that can spread rrom person ro
person. The virus that causes COVID-19 is a novel coronavirus that was first identified during
an investigation into an outbreak in Wuhan, China.
There is no specific antiviral treatment for COVID-Ig.
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ftilre2rApRrl?o3o


The purpose of the research is to determine if hydroxychloroquine combined with azithromycin
is better for treating covlD-19 than hydroxyctrloroquiir* ,loni. rne stucy will alio'oetermine if
the combination of hydroxychloroquine and aaithromycin reduces the viral load when compared
to hydroxychloroquine alone after iaking the study trJatment ior six days. Viral toad is the total
amount of virus a person has inside of them.
The combination of hydroxychloroquine and azithromycin has not been approved by the FDA for
the treatment of coVlD-lg and is experimentar in this study.
Since we do not know which study treatment is better, we will compare the study anns. Arm 1
and Arm 2 will be compared to Arm 3, which receives placebo and hydroxychloroquine. The
use of a placebo will is being done to leam which of the two study treatment works better to
treat covlo-19 and reduces virat load afier six days of study treatment.
A computer will assign you to one of the arms (groups) in the study. This is called randomization
and is done by chance like the flipping of a coin. Neither you nor the study doctor will choose
what treatment you get. You will not be told if you have been assigned to Arm 2 or Arm 3;
however, your study doctor will know. The arms are:
Arm I
Arm 2
Arm 3
. Hydroxychloroquine 200 mg
taken by mouth three t3)
times a day for 10 days
r Azilhromycin 500 mg taken by
mouth on Day 1. followed by
r Azithromycin ZS0 mg taken by
mouth once a day for four (4)
days.
Hydroxychloroquine ?00 mg
taken by mouth three (3)
times a day for 10 days
r Placebo pill Days 1{.
r Hydroxychloroquine200
mg by mouth three (3)
times a day for 10 days
Hydrorychloroqulne is approved by the Food and Drug Administration (FDA) for either
prevention or treatment oJ certain types of malaria and dutoimmune disease, such as lupus and
rheumatoid arthritis. Hydroxychloroquine has not been approved for the treatment of COVID-
19. lt has been used experimentally to treat certain people'with COVID-1g, including
hospital2ed patients.
Azlthromycln is approved by the FDA for the keatrnent of many types of infections caused by
bacteria' such as respiratory infections, skin infec.tions, ear inreitions, eye inrections, anu
sexually kansmitted diseases.
Placebo if you are assigned to Arm 3 you will receive a placebo pill for Days 1-6. on Day 6,
you will have blood drawn to check your viral load. lf you still have symptoms, you will receive
the study drug hydroxychloroquine fbr 10 days. n p6ceno piti ooejnoi nave jrnv drug or
medicine in it. lt will look 11d taste like hydroxychloioquine. ' iesearchers use a ilacebo to see
if the study drug works better than not tafing dnything_
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WHO MAY TAKE PART IN THIS STI.}OY AHO U}IHO MAY NOT?
lf you decide to take part in this study and sign this consent form, you will heve some
procedures done io see if you are eligible. you may take part in this study if:
r You are 18 years of age or older.
o You have been diagnosed with SARS-CoV-2 infection and exhibiting COVID-1g
symptoms.
You may not take part in this study if:
r You are pregnant or breast-feeding.
r You are not able to tolerate oral medications.
I You have a known allergy or bad reactions to either azithromycin or hydroxychloroquine
sulfate.
I'I'HY HAVE I BEEN ASKEO TO TAKE PART IN THIS STUDY?
You are being asked to take part in this study because you have symptoms of COVID-1g.
HOW LONG WILL THE STUDY TAKE ANO HOW MANY SUBJECTS T'YILL TAKE
PART?
You will be one of about 160 su
to be enrolled in this s
at the
lnstitute
remaln on
days
WHAT WILL I BE ASKED TO DO IF I TAKE PART IN THIS STUDY?
lf you agree to take part in this study, you will first sign this consent form. Before you are
enrolled in the study, you will have 'screening Visit Procedure.s'to determine if you are eligible
for the study' These gxam-sl tests or procedules are being perfonned because you uru taliing
part in this research study. You or your health insurance p-rovider will not be bi16d for the costs
of these tests or procedures.
Screenino Visit Procedures will inelude:
' 
Read and if you agree to take part in this study, sign this informed consent and the member
of the study team will sign. You will receive a copy of the signed and dated consent for
your records.
. Physicalexamination
. Vital signs (blood pressure, heart rate, ternperature)
r Demographic data {age, gender, race and ethnicity}
r Questions about your past medicalhistory
r Review the medications you are cunenfly taking
o Review of your COVID-19 symptoms
r An Electrocardiogram (ECG) (An ECG is a test which measures the electrical activity of
your heart to show whether or not it is working normalty)
e Urine or blood {about 2 teaspoons) for a pregnancy test
r Blood will be drawn from a vein in your arm:
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o About ? teaspoons will be drawn fiom a vein in your aml to check how your body
stores iron, eheck for brood crots and check your heart function
o About 3 teaspoons wiil be milected for this research study.
o You wil! be asked to complete a questionnaire about covlD,lg symptoms
r You will be given education on how to complete the pilldiary, and temperature log.
lf you are an lnpatient, the following will occur:
o Read and if you agree to take part in this study, sign this informed consent and the mernber
of the study tearn will sign. You will receive a copy or the signed and dated consent for
your records.
r Your rnedical record will be reviewed by a member of the research team and the following
information will be collected for the research study;
o The results of the physical examination
a Vi&al signs (blood pressure, heart rate, ternperature)
o Demographic data (age, gender, race and ethnicity)
o lniormaUon about your past medicalhistory
o The rnedications you are curenily taking
r) A Review of your COVID-Ig symptoms
r The following procedures will be performed:
o An Electrocardiogram (ECG) (An ECG is a test whieh measures the electrical
activity of your heart to show whether or not it is working nonnally)
{f, $aliva and throat swab will be mllected for the research study
o auoj Yffi,iffiffi:;ffHJ:il?H a vein in your arm to check how your
body siores iron, check for blood clots and crrecx your heart function
' About 3 teaspoons will be collected for this research study.
' 
lf you are a woman who could become pregnant, your doctor will perform
a blood pregnancy test.
r You will be asked to cornplete a questionnaire about covlD-lg symptoms
Treatment Period
lf the "Screening Visit Procedures" show you are eligible to enter this study and you agree to
take part you will be randomieed (like the flipping ofl coin) to one of three of the Arms (groups).
Neither you nor the study doctor willchoose whit treatrnent you willget. you will not be told
which arm you have been assigned to the Arm 3, however, your stuCy doctor will know.
The research nurse will review the study dnug instruefions with you.
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r
ICr l'ersron date 21APRIL2020


I Hydroxychloroquine 200 mg
taken by mouth three (3)
times a day for 10 days
r Azithromycin S00 mg taken by
mouth on Day 1, followed by
r Aaithromycin 2S0 mg taken by
mouth once a day for four (4)
days.
Hydroxychloroquine 200 mg
taken by mouth three (3)
times a day for 10 days
r Placebo pill Days 1-6.
r Hydroxychloroquine 200
mg by mouth three (3)
times a day for 10 days
Treatment Perlod - For study partielpants randomlzed to Arm I end Arm 2:
Davs 1 - 10
. Iake your sfudy drug as prescribed.
o A research nurse will collect the following information by phone or in person:
cl complete follow-up covlD signs and symptoms questionnaire
o Review your temperature log
0 Review of your pill diary
o Review of any side-efiects you msy have had
$ Record standard of care treatrnents andlor procedures prescribed
r lf you ars 1I Inpatlent, you wlll ba as*ed to complete the questionnalre. The
hospltal staff wlll glve you the study medlcatlon. A member of the research team
will review your medlcal record and lollect the followlng lnformation:
o Your daily temperatures
o The times you received the study drug
o Review of any side-efiects you may have had
o Record standard of care treatrnents and/or procedures prescribed
Arm I and Arm 2: Durlng the study treatment perlod, the followlng tests and
procedures wlll be done on the days listed below:
Dav 3. Oav 6 and Dav 10
You willretum to the study site and the follow tests and procedures willbe done:
o Repeatphysicalexamination
o Blood (about 2 teaspoons) will be drawn from a vein in your arm to check how your
body stores iron, check for blood ctrots and check your hlart function (Day 5 only)
o Blood (about 3-1/2 teaspoons) will be drawn for the research study (Day 3 and Day 6
only)
r saliva and throat swab will be collected for the research study
. Review your temperature log
r Review of your pill diary
. complete follow-up covlD-19 signs and symptoms questionnaire
Page 6 of20
r
ICF version dare 2lApRIL2020
Arm'l
Arm 2
Arm 3


r lf you are an lnpatlent, the hospltal staff wlll draur blood frorn a yeln for the blood
tests and the rBeearch study and swab your nos6 and throat to collect the
specimen for ths research study. You will bs asked to complete the COVID-1g
symptom questionnalre. A membar of the research team will revlew your medical
record and collect the followlng lnformation:
, Your daily temperafures
. The times you received the study medication
. Review of any side-effects you may have had
' 
Record standard of care treatrnents andior procedures prescribed
Dav 11-20 - Dallv Follow-up
r A research nurse will collect the following infonnation by phone or in person:
0 Review of symptoms
o Review your tempera&re log
0 Review of your pill diary
o Adverse events
s Record standard of care treatrnents and/or procedures prescribed
Treatrnent Perlod - For studv parficlnants randomlzed to,{rrn 3:
Davs 1-5
-
e Take the placebo pill
r complete follow-up covlD-19 signs and symptorns questionnaire
o A research nurse will collect the following information by phone or in person:
(:, Review your temperature log
o Review of any side-efiects you may have had
r: Record standard of care treatments and/or procedures prescribed
. You will be asked to complete the COVID-19 symptom questionnaire. A rnember of
the ressarch team wlll revlew your medlcal record and collect the followlng
lnformatlon:
0 Your daily temperatures
() Review of any side-eflects you m6y have had
s Record standard of care treatments andlor procedures prescribed
Dav 3
You will rsturn to tha study site and havs the following tests and procedures:
. complete follow-up covlo-ig signs and symptoms guestionnaire
e A research nurse will collec{ the following information by phone or in person:
0 Review your temperature log
a Review of any side-effects you may have had
* 
Record standard of care treatments and/or procedures prescribed
o Blood (about 3-1/2 teaspoons) wifl be drawn for the research study
r saliva and throat swab will be collected for the research study
2IAPRILzOSO


r lf you are an lnpatlent, the hospital staff wlll draw blood frorn a veln for the blood
tests and the resaarch study and swab your noss and throat to collect the
specimen for ths research study. you wltl be asked to cornpleto ttre COVIO-1g
symptom questionnalre. A membgr of the research team rrill revlew your medical
record and collect ths followlng inforrnafion:
0 your daily temperatures
o Review of any side-effects you may have had
o Record standard of care trealrnents and/or procedures prescribed
Dav 6
You will retum to the study site. lf you continue to have sympbms of COVID-1g, you will
receive the study treatment Flydroxychloroquine sulfate to ntigin at horne. rhe iesearch nurse
will review with you how to take the medication. You will re"Jv* a pill diary to write down the
times you take the study medication.
You will also have the following tests and procedures:
. complete follow-up covlD-19 signs and symptoms questionnaire
r Review your temperature log
r Review of any side-efiects you may have had
o Record standard of care treatrnents andlor procedures prescribed
e Blood will be dravm from a vein in your arm:
o About 2 teaspoons will be drawn from a vein in your arm to check how your body
stores iron, check for blood clots and check your heart function
o Blood (about &1/2 teaspoons) will be drawn for the research study
r saliva and throst swab will be collected for the research study
r lf you ars an lnpatlent, the hospltal staff will glve you the study msdicafion and
draw blood from a veln for the blood tests and th6 research stiroy and swab your
nose and thr-oat P-99!!*"t the specimen for the research study. you will be askod
to complete the C0VID-19 symptom questionnalre. A membei of the rssearch
team wlll review your medlcat record and collect the followlng tnformation:
o Your daily temperatures
D Review of any side-etrects you may have had
s Record standard of care treatments and/or procedures prescribed
Dav 10
You willretum to the study site and the following tests and procedures will be done:
. Take the study medication as prescribed.
r Repeat physicalexam
r Blood will (about 2 teaspoons) will be drawn from a vein in your arm to check how your
body stores iron, check for blood clots and checlt your heart function
' complete follow-up covlD-19 signs and symptoms questionnaire
r Review your temperature log
. Review of your pill diary
PaEe I of20
I
lc.h versron dare 2lAPRIL2O2O


. 
Review of any side-effects you may have had
. 
Record standard of care treatments and/or procedures prescribed
o lf you are an inpatient, the hospital staff will give you the study medicatlon and
draw blood from a vein for the blood tests. You will be asked to complete the
COVID-I9 symptom questlonnalre. A member of the research team wlll revlgw
your medlcal record and collect the followlng lnformafion:
c1 Your daily temperatures
t, The tirnes you received the study medication
o Review of any side-effects you may have had
o Record standard of care treatments and/or procedures prescribed
Oav 11-{5
r Take the sfudy medication as prescribed.
r Complete follow-up COVID-19 signs and symptoms questionnaire
r A research nurse will collect the following information by phone or in person:
D Review your temperature log
o Review of your pill diary
() Review af any side-effects yCIu may have had
s Record standard of care treatments and/or procedures prescribed
r Record standard of care keatrnents and/or procedures prescribed
r lf you are an lnpatlent, the hospltal staff wlll draw blood from a vein for the blood
tests and the research study and swab your nose and throat to collect the
speclmen for the research study. You will be asked to complete the COVIO-19
symptom questlonnalre. A msmber of the research team wlll revlew your medlcal
record and collect the following information:
o Your daily temperatures
o The times you received the study medication
a Review of any side-effects you may have had
o Record standard of care treatments andlor procedures prescribed
Day 16-20 - Dally Follow-up
r A research nurse will collect the following infornration by phone or in person:
r: Review your temperature log
cl Review of your pill diary
o Review of any side-effects you may have had
o Record standard of care treatments and/or procedures prescribed
Follow-up Perlod
The research nurse will call weekly for four (4) weeks afier the last dose of the study medication
b collect the following assessrnents:
. Review of symptorns
r Reyiew of daily ternperatures
r Adverse events
2IA}RIL3O?O


Monthly Follow-up for Stx (8) Monthe
The next five (5) months the research nurse will call you once monthly after the last dose of the
medication to colleet the following assessrnents:
. Review of symptoms
r Fleview of daily temperatures
r Adverse events
r Record standard of care treetnents andlor procedures prescribed
TIUHAT ARE THE RISKS OF HARM OR DISCOMFORTS I i,lIGHT EXPERIENCE IF I
TAKE PART IN THIS STUDY?
You may have side effects while on this study. Everyone taking part in the study will be watched
carefully for any side effects- However, doctors do not know all the side eftect that may happen"
Side efiects may be mild or very serious. Your strdy doctor may give you medicines to help
lessen side effects. Your study doctor may also decide that it is necessary to delay or stop the
study teatmenl Many side effects go away sson ater you stop taking the drugs. ln sorne
cases, side effects can be serious, long lasting, or never go away. You should talk with your
study doctor about any side efiects you may have while taking part in the study.
Posslble Slde Effects of Azlthrornycln
Common
o Nausea
. 
Vcmiting
o Dianhea
r 
Loss of appetite
r 
Stomach pain, indigestion
r 
ltching or rash
Rare but serlous
r 
lnegular or slow heart rate
o Fluttering in your chest
r 
$hortness of breath
o Sudden dizziness (like you might pass out)
. 
Muscle aches and pains
Posslble SNde Effects of Hydroxychloroquine
Common
. $kin changes, including a bleaching of hair, changes in skin pigment
r NauseE
r Vomiting
r Dianhea
r Muscle weakness (lack of strength)
. Low red blood cell counts (which make you feet tired or weak)
. Low platelet counk (which may make you more likely to bruise or bleed)
r Headaches
2IAPRIL2OSO


. Dizziness
r Eye problems, including abnormal color vision
Rare but serious
' 
Eye problems, including bluned vision, double vision, problems to the retina {flashing
lights, reading difiicutties)
r Pruritus {itching)
r Rash
r Heart rhythm change (your hear beat may be inegular or beat to fast or too slow)
Rlsks of BlEod Draws
lf.a blood sarnple is taken from you, there are few risks of harm. Possible effects from drawing a
blood sample include mild p,ain, bruising and infection at the site of needle insertion. Faintingir
lightheadedness can sometimes occur, but usually last only a few rninutes. lnfection is rare
Reproductlye Rlsks of Harm
Women of childbearinq potential
Females of childbearing potential should use reliable methods of contraception from the time of
screening until4 weeks afier discontinuing study treatment. Acceptable methods of
contraception include abstinence, tubal ligation, eombined oral, transdermal or intra-vaginal
hormonalcontraceptives, medroxyprogesterone injections (e.g., Depo*Provera), copper-banded
intra-uterine devices, hormone impregnated intra-uterine systims and vasectomised'partners.
All methods of contraception (with the exception of tiotal abstinence) should be used in
combination with the use of a condom by their male sexual partner for intercourse.
Males
Male patients rnust use a condom during sexual intercourse with all sexual partners including a
pregnant female partner during the study and for 4 weeks after discontinuing study treatmeni-
However, where a sexual partner of a male participant is a woman of childbearingpotential who
is not using effective contraception, men must use a condom during sexual intercourse during
the study and for 6 months after discontinuing study treatrnent. Male patients should avoid
procreation during the trial and for 6 months after discontinuing study treatment.
ARE THERE ANY BENEFITS TO ilIE IF I CHOOSE TO TAKE PART IN THIS STUOY?
The benefits of taking part in this study may be an improvement of your condition. However, it is
possible that you will not receive any direct benefit from taking part in this sludy. lnformation
learned from this study may help other people in the future.
WHAT ARE MY ALTERNATIVES IF I DO NOT WANT TO TAKE PART IN THIS
STUDY?
Your altemative is not to take part in this study. You may receive supportive care outside of this
sludy.
HOW WILL I KNOW IF NEW INFORMATION IS LEARI{ED THAT MAY AFFECT
WHETHER I AM WILLING TO STAY IN THE STUDY?
During the study, your study doctor will update you on if your disease is progressing, stable or
getting better. During the course of the study, you will be updated aboui any other new
information that may affecrt whether you are willing to continue taking part inthe study. lf new
information is learned that may affect you after the study or your follow-up is compleied, you will
be contacted.
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WILL I RECEIVE THE RESULTS OF THE RESEARCH?
ln general, we will not give you any individual results from the study except the details that
pertain to your condition. You will receive the COVID-19 results. lf we find something of urgent
medical importance to you, we will inform you, although we expect that this will be a very rare
occurence. For example, 'unusual findings on the blood test that we think you should discuss
with your doctor.
WILL THERE BE ANY COST TO illE TO TAKE PART IT{ THIS STUCIY?
The drugs used in this study are @mrnercially available. The study drugs will be provided at no
charge by the Rutgers Cancer lnstitute of New Jersey. You and/or your health insurance
company will not be billed f,or the cost of any research procedures, which are conducted as part
of this study.
lf you are hospitalized and being treated for COVID-19 symptoms, this is standard of care. You
andlor your health insurance will be responsible for the cost of the hospitalization, standard of
care tests andlor procedures and any co-pays related to your hospitalization or emergency
depafiment visit.
You willbe responsible for any co-payments due for office visits, co-insurances and deductibles
due on any tests and/or procedures that are required and considered standard care for the
treatment of COVID-19 symptoms.
WILL I BE PAID TO TAKE PART IN THI$ STUDY?
You will not be paid to take part in this study.
HOW YVILL INFORMATION ABOUT ME BE KEPT PRIVATE OR CONFIDENTIAL?
All efforts will be made to keep your personal information in your research record conftdential,
but total confidentiality cannot be guaranteed.
lnformation about your condition and treatment will be collected from your medical record for the
study. The infonnation will be with a study identification number and stored in a secured
electronic file. The electronic file is password protected and accessible only to authorized study
personnel.
lf information from this study is published or presented at scientific meetings, your name and
other personal information will not be used.
lf you agree to be in this study, health data that identifies you will be kept confidential. Unless
required by law, only those listed below will have direct access to your medical and study
records to check the study information:
o the
doctor and stafi
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ttltf,e2lAPRILso?o


. Government regulatory agencies throughout the world (such as the FDA).
A description of this clinical trial will be available on ClinicalTrials.oov, as required by U.$. law.
This website will not include information that can identify you. At most, the website will include a
summary of the rffiults. You can search this website at any time.
WHAT TTI'ILL HAPPEN TO MY INFORMATION OR BIOSPECIMENS COLLECTED
FOR THIS RESEARCH AFTER THE STUDY IS OVER?
The information or biospecimens cotlected for this research may be used by or distributed to
investigators for other research after obtaining additional informed consent from you" Please
referto'CONSENTADDENDA: Request to Store Tissue andlor Health lnformation for Future
Research Use".
WHAT WILL HAPPEN IF I AM INJURED DURING THIS STUDY?
Subjects in this study will be exposed to certain risks of personal injury in addition to those
associated with standard forms of treatment as described under "What risks can I expect from
taking part in this study?" ln addition, it is possible that during the course of this study, new
adverse effects that result in personal injury may be discovered. fhe University RWJ Barnabas
Health will make appropriate referrals for medical andlor dentaltreatment for subjects who
sustain personal injuries or illnesses as a direct consequence of participation in the research.
The subject's health insurance canier or other third-pafi payer will be billed for the cost of this
treatment; provided that lhe University shall not submit to federally funded programs, e.9.,
Medicare, Medicaid or CHAMPU$, for reimbursernent first if sr^rbmission to such programs is
prohibited by law. No financial conrpensation will be provided by the
Health and no other type of assistance is available from the Universi$
However, by signing this form, you are not giving up any legal rights toEl
compensation.
WHAT IAIILL HAPPEN IF I DO NOT WISH TO TAKE PART IN THE STUDY OR IF I
LATER DECIDE NOT TO STAY IN THE $TUDY?
It is your choice whether to take part in the research. You may choose to take part, not to take
part or you may change your mind and withdraw ftom the study at any tirne.
lf you do not want to enter the study or decide to stop taking part, your relationship with the
study staff will not change, and you may do so without penalty and without loss of benefits to
which you are otherwise entitled.
At the conclusion of the trial
Page l3 of30
. 
e 2IAPRIL3020


Any data that has already been sent for analysis cannot be withdrawn because there may not
be any identifiers with the data.
At any time, the study doctor can take you out of this study if it would not be in your best interest
to stay in it. Your study doctor can stop treatment even if you are willing to stay in the study if
medically indicated.
lf you decide to withdraw fom the study ior any reason, you may be asked to retum for at least
one additional visit for safety reasons.
WHO CAN I COTIIT,ICT IF I HAVE QUESTIOIII$?
PERMISSION (Authorizatlon) TO USE OR SHARE HEALTH INFORMATTON THAT
IDENTIFIES YOU FOR A RESEARCH STUDY
lnformation about you and your health is personaland private, so this information generally
cannot be used in research without your written permission. The next few paragraphs tell you
about how researchers want to use and share your health information in this research study.
Your information willonly be used as described here or as allowed or required by law. Ask
questions if you do not understand any part of the research or. the use of your health
inforrnation, lf you sign this consent form, you agree to let the researchers use your information
in the research and share it with others as described below.
What ls the purpose of the research and how wlll my lnformatlon be used?
You are being invited to take part in this research study, which is described at the beginning of
this fonn. The purpose of collecting and using your health information for this study is to help
researchers answer the questions that are being asked in the research.
What lnformatlon about me wlll be used?
r Allinformation in your medical record
r Hospitaldischargesummaries
r Laboratory, x-rays, CT scans and test results
r Medical history or treatment
r Medications
Page l4 of20
m;e2rAlRrl2o2o


r Laboratoryldiagnosile tests or imaging
. Operative reports (ahout a surgery)
r Emergency Medicine reports
tlYho wlll s€6 rny medical information?
Your privacy is very important to us and the researchers will make every effort to protect it. Your
information may be given out it required by law. For example, certain states require doctors to
report to health boards if they find a disease like tuberculosis. However, the researchers will do
their best to make sure that any infonnation that is released will not identify you. Some of your
health infonnation, and/or information abaut your specimen, ftom this study will be kept in a
central database for research. Your name or contact information will not be put in the database.
There are organi:ations that may inspect your records. These organizations are required tro
make sure your information is kept private, unless required by law to provide information. Some
of these organizations are:
r The Office for Human Research Protections in the U.S. Dept. of Health and Human Services
o The Food and Drug Administration
l/Vho ttlay Ure, Share or Receive [t{y Information?
The research team may use or share your information collected or created for this study with the
that receive your information may not be required by Federal
share your information with others without your permission, if
permitted by the laws goveming them.
l{fill I Be Able To Revlew My Research Record Ytlhlle The Research ls Ongolng?
No" We are not able to share information in the research records with you untilthe study is over"
To ask for this information, please contact the Principal lnvestigator, the person in charge of this
research study.
Do I Have To Glvs My Permlsslon?
No. You do not have to pernrit use of yor.rr infonnation. But, if you do not give permission. you
cannot take part in this study. (Saying no does not stop you frorn getting medical care or other
benefits you are eligible for outside of this study.)
Page l5 of20
ttlH,e2lAlRIL?o?o

ICF_003.pdf: 
Official Title:
Ra ndom ized Compa rison of Com bination Azith romyci n
and Hydroxychloroquine vs. Hydroxychloroquine Alone for
the Treatment of Confirmed COVID-19
NCT number:
04336332
Document Type:
Consent-Main
Date of the
Document:
04/21./2020


longer be used or shared in the study, but we will not Ue itite to take back information that has
been used or shared with others. lf
now but
mind later for use
How Long Will My Permlssion Last?
There is no set date when your perrnission will end. Your health information may be studied for
many years unless you have not agreed to allow your data and leftover specimens to be utilized
for future use.
!t ls?y Yes Now, can I chango My Mind And rake Away My permisslon Later?
Yes' You may change your mind and not allow the continued uie of your information (and to
stop taking part in the study) at any time. lf you take away permission, your infonrration will no
AGREEMENT TO PARTICIPATE
Subiect Consent:
-
I have read this entire consent form, or it has been read to me, and I believe that I understand
what has been discussed. All of my questions about this form and this study have been
answered. I agree to take part in this study.
Subject Name (Print):
Subject Signature:
Date:
Sionature of lnvestiEator/lndlvidual Obtaininq Consent:
To the best of my ability, I have explained and discussed all the important details about the
study including all of the information contained in this consent form.
lnvestigatorlPerson Obtaining Consent Name (print):
Signature:
Date:
Page 16 of?0
ffi*?lApRrL2o?o


CONSENT ADDENDA:
Request to $tore Tlssue andlor Health lnforrnatlon for Future Research Use
This section of the informed consent form is about additional research that is being done with
people who are taking part in the main study. You may take part in this additional iesearch if
you want to. You can still be a part of the main study even if you say 'no' to taking part in this
additional research.
We ask your permission to store samples and health information collected from you during the
main study "Randsmlzed cornparison of combinatlon Azlthromycln and
Hydrcrychloroqulne vs. Hydroxychloroqulne Alone tar the lreatmenf of Conflnned
COVID'1fl for future research. You may still participate in the main study even if you say no to
this request to store your samples and information for future research.
The types of research that may be performed on specirnens obtained from this include analysis
of genetic information (DNA or genes), proteins, and/or cell behavior in a test tube.
Observations made on genes, proteins, or cells will be linked to clinical information to make
associations with risk of developing cancer, response to therapy, side effects of therapy, or with
specific cancer outcomes. DNA is the material that makes up your genes or genetic information
that you inherit from your parents. Genes are also important in determining the occurrence of
cancer and how they respond to cancer treatments. Other types of analyses done on specimens
may include measuring the levels of proteins or RNA (a rnaterial that helps form the ternplate
from which proteins are made) in cells, in body fluids or in tissues. Cells may be processed so
that they can be kept in culture short term, injected into animals to observe cell behavior, or kept
in culture indefinitely. Cells kept in culture allow for a renewable source of DNA, RNA, proteins
and cells that can be used to test response to therapies in a test tube_
HOW AND WHERE wlLL MY BIOSPECIMENS BE STORED A}ID BY WHOM?
is to better understand and develop better means to
prevent, diaEnose and treat disease.
All of the subjects in this study will be asked to allow leftover blood to be stored and used for
future use in the repository.
There is no set limit to the number of individuals that may provide samples and information to
the repository. The more samples and health information available in storage, the more useful
the repository will be for medical research.
HOW WILL TISSUE SAMPLES A,ND INFORMATION BE COLLECTED?
We use the terrn "tissue" to refer to specimens such as blood, saliva and throat specirnens that
were collected as part of this research study. We ask your permission to store left over tissue
samples and health information that was colleeted during this research study for future
research.
Please know that you rnay still participate in the main study even if you
store tissue for future research. we will also coffect information about
reports for future research. only the leftover tissue that was collected
Page l7 of20
ilt*2rAlRr,.?o,o
say no to this request to


study for future research would be stored and used for future use.
i111c!.ologlcal or social Rtsks AssociatEd wlth Loss of privacy:
While the databases developed for this project will be coded to protect y6ur personal
infonnation, people may develop ways in the future that would allow someone to link your
medical information back to you. lt is also possible that there could be violations to thi security
of the computer systems.
Although your genetic information is unique to you, you do share some genetic information with
your children, parents, brothers, sisters, and other blood relatives. Conslquenfly, it may be
possible that genetic information from them could be used to identify you. bimitirly, it may be
possible that genetic information from you could be used to help identiff them. Further, pattems
of genetic variation also can be used by agencies to identify a person or nisffrer blood relatives
{for example, to establish relationships between parents and thear children}.
There also may be other privacy risks that we have not foreseen.
Economic Risks of Harm
$ince some genetic variations can help to predict the future health problems of you and your
relatives, this information might be of interest to health providers, liie insurance tompanies, and
others. Therefore, your genetic information potentially could be used in ways that could cause
you or your family eeonomic distress.
There are state and federal laws that protect against genetic discrimination:
There is a federal law called the Genetic lnformation Nondiscrimination Act (GINA). ln general,
this law makes it illegalfor health insurance companies, group health plans,'and most
employers to discriminate against you based on your genetic information. This law generally will
protect you in the following ways: (1) health insurance companies and group health plans may
not request your genetic information that we get from this research; (2) heaith insurance
companies and group health plans may not use your genetic information when making
decisions regarding your eligibility or premiums; and (3) ernployers with 15 or more employees
may not use your genetic information that we get from this research when making a decision to
hire, promote, or fire you or when setting the terms of your employment. Howevei, it does not
protect you against discrimination by companies that sell life insurance, disability insurance, or
Iong{erm care insurance.
WHAT ARE THE BENEFITS OF PARTICIPATION?
You will not benefit personally from providing biospecimens and health information for this
Repository because research usually takes a long time to produce meaningful results. However,
your participation may help investigators undersiand, prevent, or treat the diseases and
conditions studied in the future.
HOWWILL INFORiilATloil ABOUT ME BE KEPT PRIVATE ANO CONFIDENTIAL?
IS THERE OTHER IMPORTANT INFORMATIOH TO CONSIDER?
Page l8 of30
t!t;e2rApRr,-?o?o
KEPT PRIVATE ANCI CONFIDENTIAL?


Yes. There is no cost to you to take part in the Research Repository. Nor will you be paid to
take part in the Repository. lt is possible that future research using your biospecimens may
lead to the development of new tests, techniques, drugs or other commercial products. Should
any products or services result from future research, there is no plan to share any of the profits
with you.
I 
Your Rights lf I Agree To Take part ln The Research Reposttory?
You havEthe right to ask questions about any part of our storage and future research at any
time. You should not sign this form unless you have a chance to ask questions and have been
given answers to all of your questions. Your participation in the Research Repository is
voluntary. You do not have to participate. lf you do, you can change your mind at any time.
Yes }{ow. Can I Ch
Mlnd And Take
Permlssion Later?
Please tell us if and how you wish your lbiospecimens and information to be used for future
research. Please add your lnltials to indicate the ways you permit your samples and information
to be used:
My blood specimen and health information may be used for future research as follows:
only on Disease related to cancer, infectious diseases, cardiology
on any research topic important to researchers
WHO CAH I CONTACT IF I HAVE OUESTION$?
Page 19 of?0
H;.2rApRrl2o2o


AGREEMENT TO PARTICIPATE
Sublect Consent:
ry
I have read this entire consent form, or it has been read to me, and I believe that I understand
what has been discussed. All of my questions about this form and this study have been
answered. I agree to take part in this Research Repository.
Subject Name (Print):
Subject Signature:
CIate:
Slqnature of lnvestlqator/lndlvidual Obtalnlno Consent:
To the best of my ability, I have explained and discussed all the important details about the
study including all of the information contained in this consent form.
lnvestigatorlPerson Obtaining Consent Name (print):
Signature:
Date:
Page 30 of10
me2lAlRIL2o?o

Prot_000.pdf: 
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

SAP_001.pdf: 
OfficialTitle:
Randomized Comparison of Combination Azithromycin
and Hydroxychloroquine vs. Hydroxychloroquine Alone for
the Treatment of Confirmed COVID-19
NCT number:
04336332
Document Type:
SAP
Date of the
Document:
0s/0812020


6.{ Data Analysis
Statistical considerations
We follaw Gautret et al. {20?0} in using, as a primary endpoint, absence of viral evidence of disease
six days folloring start of teatrnenl. ln that study {Table 3}, there were 14 patients feated witfr
hydroxychloroquine alone, and 8114 (57.1 percent) of Srem were virus-fiee at 6 day*. There were six
patients Seated with bcth hydroxydrloroquine plur aai&rorny*in, and all six {100%}were virus-tree at
6 days. ln a lhird group cf patienk wi*r no hydroxychforoquine, *rere were 1 G patients, of whorn 2
{12.5 percent} were virus-*ee at 6 days.
We propose a three-arrn trial as follows: Arm 1 (HCQ + AZ), Arm 2 (HCQ alone), and Arm 3 (delayed
HCQ), with patienb randornized 2:2:1. Ann 1 will be compared to Arm 2, and *rm Z to Ann 3. A toial
of 160 patients will be accrued, with 60 patients in Armr 1 and ! and 30 patients in Arm 3. The
additional 10 patients accrued are to acsunt br potential drop out of subjects. An interim analysis
forfulilitywill be canied out et the 50% target accrual point, which is after 75 patients have been
enrolled. Randomization will be stratlfred on {A) ingatient vs out-patient, and {B) severe vs not
s€verB, as defined in $ection 1,3 to ensure that these factor* are balanced arnong all three anns.
l{ce + AZversus HCe alone
The primary outcome is a comparison of fum 1 to Arm 2, with Sre aim of determining if the addition of
AZ to HCQ is effective. The primary endpoint is the propofiion of patients that are virus-free at 6 days-
We assume that tha proportion of patients in the hydroxychloroquine arm who are virus-fiee at 6 days
is 0.571, and that the trial is stopped frr &rtilig at the 50% accrual point if the conditianal power at *rat
time is belcw 0.15. The following table shows the power of detecting an improvement in the outcorne
for a range of proporlions vlrus-tee in the combination arm.
For example, with 60 patienis per annr we could detect, with 80 percent power, an increase in the
puportion of virus-fiee patien6 from 57,1 percent in the hydroxychloroquine arm to 80.5 perc*nt in
the combinalion arm. The loss of power associated with using futilig stopping ls only 0.19 percent.
The two-sided Type I enor probability associated wifr this test is 0.05. We will use an unwnected
chi-squared statistic to evaluate this null hypothesis.
HCfi versus placebo and delayed FIGQ
A second, independent goal of the shrdy is to ensure that, in fact, hydroxychloroquine is efiectivE in
reducing viral load" Thus, we plan a &ird, sontrolarm, in which patients will receive a placebo for six
days, at whlch time they will switsh to receiving HCQ. We ptan to compare Arms 2 and 3, with lhe
Proportion virus-fee
(HCQ only)
Proportion virus-
tee HCO plus
Proportion
differense
Power no
futility
stopping
Loss of power with
futility stopping
(simulation)
0.571
0.805
0.234
0.800
0.0019
CI.571
0,820
0.249
0.851
0.0016
4.571
0.820
0.349
0.882
0.0013


having 30 patients and the HCQ arm having 60 patients, as above. Based on the
Gautret et al" study [9J, we assume the ba*eline proportion of patients who are virus-free at six days
is 0.125. The following table shows the detectable difference with a varlety of baseline rates:
Thus, for a range of plauslble virus.tree rates for the HCQ arm, the detectable rate fur the HBQ arm is
well wi*rin the range reported by Gautret et al {91" The futili$ analysis has a negligible effec't on
power.
Futility rtopping rule
This clinicaltialwill use a non-binding futility $topping rule based on conditional power [301" Atthe
509& accrual point (75 patients), an inEriln analysis will be canied out and the conditional power of
the prirnary Fnn I vs Arm 2) and secondary (,qrm 2 vs Arm 3I calculated. A dala msnitodr{l
committee will review *re analy*is tn dete*xlne lf accrual to any of the arms should be sbpped for
tutility.
Other analyses
A key secondary endpoinl will be the number of days ftom initiation of therapy to VNO {virtually no
disease). This can he displayed graphically using Kaplan-Meier survivalcurves, and fonnally
assessed usilg a log,'rank test. Other semndary endpoints that can be a$essed in this way are {1}
Time in daye to being afebrile for 48 hours, (2) time in days to resolution of symptoms {as assessed
by a symptom questionnalre), (3) time in days to discharge (if hospitalized), {4} time to recovery {able
to retrm lio work or school), and (5) time to deatr from COUD-19. Other measureE that will be
a*sessed via deseriptive statistice are agent ioxicity, adverse evenE, and improverfient over tirne in
vitalsigns.
The effects of additional clinical variables on the pnmary outcome and other binary outcomes will be
assessed via logistic regression. The efieets of tfrese variables on survival endpoints will be assessed
via the Cox proportionalhaeards model. Numbers of patient death* due to COVID-19 in the thrae
arms will be compared using tests cf proportions, and via log-rank test comparison of Kaplan-Meier
survivalcurves.
Porvgr calculation methods
Porer calculations were canied out using the PS sample rize program [21]. Conditional power at the
interim analysiswas computed using *re method described in Jitlal et al" [20]. Estimates of loss of
power due to fte use of a non-binding conditional po,ver futility boundarywere computed via a
simulatbn of 10,000 replications of a clinieal trialwith the null and altemative hypotheses as specffied
in the above power tables. For *re simulated p{rwer calculations lve assurne an int€rim analysis at tie
50% accrual time, and stopping if the probabili$ of a statistically significant result (two-sided p-value
< 0.05) is below 15%, based sn a conditional power calculation [20]"
6.2 Data Seeurity
Proportion virus-fee
Control(delayed HCQ)
Proportion virus-
ftee l'lCQ
Proporlion
differenee
Power no
futility
stoooino
Loss of power with
futility stopping
(simulation)
0.r25
0.401
0.276
0.800
0.0005
0.125
0.420
0.24S
0.848
0.0003
0.125
0.430
0.349
0.870
0.0005


Oata will be entered into eleckonic case report forms {eCRFs} through Ongore6 which ie the Cancer
lnstihrte's clinicalkials.management systern. Thesa *CRFs aie used-to record subjecf data generated
by subject events: t!,pically labs, study medica$on adminlssatiqn or procedures of the piotcioi. eacfi
user acce$ses the soflr,vare using-his/her Rutgers Net lD and password. users are given e#ss or
permission to various areas of onCore& based an their rol* withln the Cancer lnsttutefl.e., d;ta &q/,
reUglalcry, stu{ coordination}. Audit trails are built into lhe sofruare to track when data entry wjd
started' when the fonn was declared complete, when the form was rnonitoredlqueried, amende6, and
then finalized. On6ore& also funclions as an honest broker and has the cababilry to providi de-
identifted datia reports to the prineipal investigator or designee for analysis.
6.3 Oata and Safety ltlonitoring
A. Datrl$afety Monitoring ptan
The Frincipal lnvestigator will be responsible icr manitaring the data, assuring protocol compliance,
and conducting *re safety reviews at the specified frequency, whieh must be conducted al a
minimum of onee a month {including when re-approval of Sre protoml is sought}. The Ruegr
Caneer lnstitute of New Jersey's Human Researeh Oversight Committee (HROC) will be the DSMB
of record. During the review process, the principal invest(ators (serving as monibrlwill evaluate
whether the study should continue unchanged, require modification/amendmenl, or close to
enrollment. Eifter principal investigator, IRB or eilher Data or Safeg Monitoring Committee have
the authority to stop or suspend the study or require modifications at each instiMion. The pls will
be responsible for sharing this informalion in a timely fashion and mordinating appropriate parallel
actions at the other in*titution.
An auditwillbe conducted following enrollmentof the firsttwo {2) orthree (3} patienis. Subsequent
audits will occur dependent on the rate of enrollment by each participating site. More freguent
audits of patient data and study conduct will occur if necessary. Prior audit findings and/or
situations that may arise during the study will determine the need for more frequent auditing" All
audit findings will be discussed with the principal investigator and report the HROC and the Rutgers
Universig lRB.
B. Satal$afety Monitoring Baard Details
6.4 Reporting Results
A. lndividual Subiects' Results


Hffil"dividual patient as$essments will be shared wtth the individual patient as these are
-- -,r 
^t --. .r:-- 
^^-^ 
Ja*lallr
;fi:?ir:J ;[ffiffilI;io anc i*pa"t me.oicat *uti. tr"r" resuhs are part oi routine care (sarery
Lbs, routine radiology procedures, and physical examinations)'
B. Aggregate Results
nI[red'ate research results will not he shared with the study participants.
C. Professional
S.5 Secondary Use of the Data
N/A
D. ClinicalTrial" Rsgistiition, Results Reporting and Consent Posting
Cii*"iffriafr.Ccv Registration and Data Reporting: Under the terms"of the Food and Drug
lUminis*aUon fufoOernBition Act (FDAMA)'and ttie Food and DrugAdrniniskation Amendmenk
A;i iFuRli,-trre Sponsor ;t th; triil is soteiy responslble ftr qqleJmiryng y[ethelthe trial and its
i"",]tr "i.iubjeci 
to the requirements for iubmission to the clinical Trials Data Bank,
i,ttpii*r*."flni,*ft i"f*.gor.'information posted will allow subjects to identi$, potentially .
;iffiiseaseconditionsandpursueparticipationbycalling'acentral,contiact
nllnulr, tor turther intormaiion on appropriate trial"locations and trial site contact infonnation'
This is a research study which prospectively assigns hurnan farticipants to health relatad
interventions. The stug *iii U* r.E*t red on cfinLaftr:ials.gov per FDA Regulations wiihin ?1
Uiyu'of .ntollment of the first participant and updated at laast every 6 rnonth'
;i,,i iiiiii,'ui l:+,s\ int,,rr1iffi|l|i:
TT''ffi'ffi]gi{ffi'frffiio wc, rans HJ, Hsueii R."3ieviiie acute &rraio.y- av"1t3Tl coionivirus 2
BnnS-CoV-e1 anA oronavinfi disease-2019 (COVID-19]: Tha epidemic,lE !h9 -challenges. lnt J
A,ntimicrob Agents. n020 Feb 17:105924. Uoi: iO"tOtg/j"ijantimicag.2020.105924. [Epub ahead of
printl.
8.0 ApprovalslAuthorizations


4.
Wang LS, Wang YR, Ye DW, Liu QQ. A review of the !019 Novel Coronavirus (COVID-I S) based on
cunent evidence" lnt J Antimicrob Agents. 2020 [Epub ahead of printl.
WHO Director-General's opening remarks at media briefing on GOVID-19 * 11 March 2020,
[httpslfu*+w.who.inUdgr/speeches/detaillwho"directorgeneral-s-opening-remarks-at-the media-
briefing-on-oovid-1 9-1 1-march-303{t
Wu Z, McGoogan JM. Characteristics of an imprtant leslon fiom the coronavirus disease?019
{SOVID-I9} ouhreak in China: summanf of a report o172,314 cases from fre Chinese Genter for
Oisease 6on*ol and Prevention. JAMA. 2020 Feb 74- CIoi: 10.1001/jama-V.fr20.2M8. [Epub ahead
of pnlll.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al" Remdesivir and chloroquine effectively inhibit
the recentty ernerged novel coronavirus {2019-nCoV} in v}tro. Cell Res 2020; 1&0292.
Gao J, Tian Z, Yang X. Breakthrough: Chbroquine phcsphate has shor,,m apparent etrtcary in
treatnrent of COVIO-l9 asssiated pneurnonia in clinical stxdie*. EioEci TrendE 2020 Feb 19" Doi:
10.558t/bst20202.0147. lEpub ahead of pfint].
Chinese Clinical Trial Registry. httpfArww.chluk.org.sn"
Zhonghua Jie He Hu X Za Zhi. Multicenter collaboration group of Deparfinent of $cience and
Technology of Guangdong Province and Health Commission of Guangdong Frovine for chlonrqulne
in the keJtinent of n&el coronavtrus pneumonia. Expert consensuE on chloroquine pho*phate ior&e
treatmentof novelcoronavirus pneumonial. 2020 Mar 12;43 {3}:18S188.
doi:1 0.3760icma j-issn. 1 00 I -0939"2020.03.009.
Gaufet P, LagierJ-C, Parola P. et al. Hydrorychloroquine and azithromycin as a beatmenl of
COVID-1$: results 6f an apen-lahel non-randornized clinical trial. lnt J Anfimicrob Agenfs 105S49
t!0201 doi: 1 0. 1 01 6lj. ijantirnicag.!020. t 05949.
10. Bbt C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, et al. Designandsynlhesisof
hydroxyfenoquinederivatives with antimalarial and antiviml activities. J Med Chem 2006; 49:2&{&
2849.
11. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. Annerican Acaderny of Ophthalmology.
Remmmendations on Screening for Chl*roquine and Hydroxychloroquine Retinopatht PO16-
Revision). Ophthelmology. 2016 Jun; 123(0):1386-94. dni: '10.10161j.ophtha.2016.01.0S8. Epub 2016
MarIS.
1?. Yao X, Ye F, Zhang M, Cr,li C, Huang B, Niu P, et al. ln Vito A,nfiviral Activi$ and Proiection of
Optimized Dosing Oesign of Hydroxychloroquine ior the Treatment of Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-CoV-2). Clin lnfect Dis. 2020 Mar 0. pii: ciaa237. doi:
10.1093/cideiaa?37. [Epub ahead of print].
13. Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Ojiane J, BrouquiP. Treatmentof Q
kver endocarditis: comparison of 2 reglmens containing doxycycline and ofloxacin or
hydro{fchloroquine. Arch lntem Med. 1999 Jan25; 159 (3):167-73.
Protocn{ Ti[e: Cll.il 002011: Azittuu*ycir md
Hydroxychkroquine vs. Hydroxyd{oroqulne lor Trsatment of
Contumod COVID-IS
Prolocal Vershn Oate: 0&May-20fl)
Page 36 of '18
5.
6.
7.
8.
L


14. Lagbr JC, F,aoult D" lr\lhipple's disease end Tropheryrna urhippiei infedigns:,wfrEn to su$pectthffl
ani how to diagnosa and ireat thenr. Cun Opin lnfect Dis. 2018Bec; 31{6}:463470' {oi:
10.1W?/QCO.OOOOOOOOAO000489. 
[x] Expert consensu$ on chloroquine phoxphate for the teatrnEnt
of novel coronavirus pneumonia.
15. Amrskong N, Richez M, Raqrlt D, Chabriere E. Simultaneous UHPI-C-UV analysis of
hydrorychhroquine, minocyeline and dorycycline from serum ramples fortlre therapeuticdrug
rnonilorfng of Q fever and Whipple's disease. J. Chromatogr. B Analyt. Technol" Biomed. Life Sci.
2017: 1060,18&172.
16. Ztrou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical sourse and risk iactors for mortellty of adutt
inpatients with COVI&19 in Wuhan, China: a rehospec{ive colrort study..Langt 2Q2p Mar 11" pii:
50140{738{20}30586-3. doi: 10.10161S0140.6736(20}30566-3. lEpub ahead of printl.
17. Retallack H, Di Lullo E, fuias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, et al. ?ika virus cell
tropism in the developing human brain and inhibition by aeithromycin. Froc NaS Acad $ci USA. 201S
Dec 13; 113 (50): 144CI8-14413. Eptrb 2016 Nov 29.
ls.Booseboeuf E, Aubry M, Nhan T, de Pina, JJ, Rolain JM, Raouh D, et al. *=inryryygl.-
inhibits ttr* replication of Zika virus. J Antivirel* Antiretrovirals. 2018 10(1):&11" doi: 10.417?1948-
5964.1000173.
1g. Bacharter LB, Guilbert TW, Mauger DT, Boehmer $, Beigelman A, Fitrpatriek AM, et al.
Early adminisbation of azithromycin and preveniion of severe lower respiratonT tract_illnesses in
preschool children with a history of such illnesses: A randomized clinicaleial. JAMA. ?015 Nov 17;
314(1 9):2034-!044. doi:1 0. 1 00 1{ama.?01 5. 1 389€.
30. Jitlal M, Khan I, Lee SM, & Hackshaw, A. &pping clinical trials early forfutility: retospec-tive
analysis of seyeral random*aed clinical sMies. Bl'. J Cancer 107, 910-917 {20f 2}.
http://dx.doi"orc/1 0/1 038%Fbic.201 ?.M4.
21. Dupont, WD & Plummer Jr., WS. Pcwer and sarnple size calarlalions: A *i9y 1S *mputel -
program. ControtClin Triats 11,'t16-128 {f990). http:l/dx.doi.orol10.1016%2F0197-245S(90F0005'
M
23. Woosley, R. L., Heise, C.W., G*llo, T., Tate, J., Woosley, D., & Rornero, K. A. {i013}" QTdrugs List.
Retieved May 7, 2020, from vrunr.CredibleMeds.org


CBCD, CfiP, Ferritin,
0-Oimer, LSH and
Azithrornycin (Arm
1I
1.
2.
3.
4.
Trrstrnent will be edrfiinister€d Dey 6 to 015 for Arm 3'
Plrone *srersments - weetty x rt week t+/- one day).
phone e!s*{*rn*nt! * mofithly x 6 monthr (+/' one rreek}'
Scprning and Say 1 vi*itr rnay bc wnrhined, All Froc*durcr may be romptreted wi&in 24 hu$s of rw*ning virit
Saliva, Oropharynx
swebs
0aily Temperature
Review
Record other SOC
Frocedures


Appendix B
a known or
risk of QT
Drug class
Knonrn risk
Possible risk
ADHD
Atornoxetine
Alpha-blocker
Atfuzosin
Analgesic
Hydrocodone-ER
Tramadol
Anesthetic, general
Propofol
Sevoflurane
Anti-androgen
Degarelix
Leuprolide
Antianginal
Eepridil
AnUanhythmic
Amiodarone
Disopyramide
Dofetilide
Dronedarone
Flecainide
lbutilide
Procainamide
Quinidine
Sotalol
Antibiotic
A,zithromycin
Clarithromycin
Erythromycin
Ciprofloxacin
Levofloxacin
Moxifloxacin
Bedaquiline
Gemifloxacin
Norfloxacin
Ofloxacin
Telavancin
Telithrornycin
Lefamulin
Anticancer
Arsenic trioxide
Vandetanib
Cesium Chloride
Encorafenih
Toremifene
Dpirubicin
Fluorouracil (5-fU)
Oxaliplatin
lnotuaumab ozogamicin
Sasde$b
Midostaurin
Ribocictrib
Tarnoxifen
Eribulin m*sylate
Lepatinib
Osirnertinib
Capecitabine
Sunitinib
Bosulinih
Dasatinih
Nilotinib
Bendamustine


Drug class
Known risk
Possible risk
$orafenib
Ceritinib
Entreetinib
Necitumumab
Cobimetinib
Dabrafenib
Vemurafenib
TipiracillTrifiuildine
Crizotinib
Caborantinib
Faaopanib
Lenvatinib
Vorinostat
Tazemetosbt
Romidepsin
Vorinostat
Fanobinostat
lvosidenib
Apalutamide
Bortezomib
Anticoagulant
Betrixaban
Anticonvulsant
Eaogabine
Felbamate
Antidepressant, SNRI
Venlafaxine
Antidepressant, $SRl
Citalopram
Escitalopram
Clomipramine
l-ilhium
,Antidepressant, Tetracyclic
Meprotiline
Mirtazapine
Desipramine
lmipramine
Nortriptyline
Trimipramine
,Antiemetic
Ondansetron
Droperidol
Chlorpromazine
Dolasetron
Granisteron
Palonosetron
Promethaeine
Antitungal
Flueonazole
Pentamidine
Antihypertensive
lsradipine
Moexiprillhydroshlorothiazide
Nicardipine
Anlimalarial
Chloroquine
Hydroxycholcrquine
Artenimoypiperaquine
Artemetherllum efantri ne
Antimanic
Lithiurn


Drug cla*s
Knourn risk
Possible risk
Antineoplastic
Giltertinib
Antipsyehotics
Droperidol
Chlonpromazine
Haloperidol
Pimoaide
Thioridazine
Perphenazine
Promethaeine
Pimavanserin
Asenapine
Cloeapine
lloperidone
Lumateperone
Paliperidone
Lurasidone
Aripiprazole
Antisense oligonucleotide
Nusinersen
Anlitubercular
Pretornanid
Antiviral
Efayirenz
Lopinavi#Ritonavir
Rilpivirine
Saquinavir
Antispasmodic
Mirabegron
Cholinesterase inhibitor
Donepezil
Dopamine aEonist
Apomorphine
Estrogen agonisUantagonist
Toremifene
Glucosylceramide synthase inhibitor
Eliglustat
Gonadotropin receptor
agonisUantagonist
Leuprolide
Gonadofopin-releasing hormone
agonistlantagonist
Degarelix
Histamine H2 receptor antagonist
Famotidine
Histamine 3 antagonisUinverse
Pitol isant (Tiprolisant)
lmmunosuppressant
Tacrolimus
lrnaging mntrast agent
Perfl utren lipid microspheres
lllieit druEs
Cocaine
Muscle relaxants
Tieanidine
Tolterodine
N MDA receptor antagonist
Memantine
CNS $timulant
Atomoxetine
Oxytocic
Oxytoein
Opiates
Methadone
Buprenorphine
Phosphodiesterase 3 inhibitors
Anagrelide
Cilostazol


Drug class
Known risk
Possible risk
Fhosphodiesterase 5 inhibitors
Vardenafil
Progesterone antagonist
Mifepristone
Sedative
Dexmedetomidine
Somatostatin analog
Pasireotide
Sphingosine phosphate recepior
modulator
Fingolimod
tJnknovyn
Dextromethorphan/Qui nidine
Vasodilator, Coronary
Papaverine HCL
(lntracoronary)
Vesicular monamine tansporter 3
inhibitor
Deutetrabenazine
Vesicular monamine tansporter 2
inhibitor
Valbenazine
Vesicular monamine fansportrar 2
inhibitor
Telrabenazine


Appendix C
CINJ 002011 COVID-l9 Baseline Questionnaire
Your Madlcal Hlrtory
Are you complating thir Bassline Questiannaira online or in person at E
a study site? 
tl
indicata
EIn
nn
trn
trn
fIn
ntrn
Medicine I
Medicine 2
Medicine 3
Medicine 4
Medicine 5
Medicine 6
MedicinE 7
if you heva been diagnosed with ortrsetBd forone or mors of the following conditions:
Fitbeter mallitus
High blood prsseure or hypertansion
Asthma
Chronic bronchitis, amphysema. or chronic obstructiva pulmonary disaese {COPB}
Anot*rer chronic lung disease (spacifu ):
coronary artery disease, peripharal artery disease, angina, or heart attack (myocardial
infrrction)
Cnngestive heart failurp
Itrska or transiant i*clrsmic atttck {TlA}
Akialfibrillation
Cancer oth*thsn non-melanoms skin cancsr
Chronir *idney disease {fl(D}
Crohn's di**asa, ulcerativa colitir, nr infitmmatory bowel diseasa {lBD}
Rhaumatoid arthritis {RA}, psoriasis, systemic lupus, multiple sclerosis, or anothar disordEr
farurhich yuu tak* medicina to lower your imrnune syetem {immunorupprsssent}
Flsase write the nartes of alltha msdicinss you have taken in ths last wea( including ouar-the-counter medicines,
supplements, probiotics:
Online
ln person at rtudy sita
Medicine I
Medicine I
Medicine 10
Msdicine 11
Medicinp 12
Medicine 13
MedicinB 14
List any other medicines you take here, separated by commas.
Pags 6 of48


Doyou avertrka r probiotic? tr 
0, Never
n 
!., Occaoionally, such as whan I take entibioticr ur have disrrtree
n 
2, Ysr, ragulerly
Hava you ever received pnaum$coccal vsccin* {Provnar-13 or Fneumovax-23}?
nun
ln the last week, have you had a new fever > 100" F?
ln the last week, have you had a new cough?
n o,Nc
n l,Yas
ln the last week, have you felt new shErtness of breath or had new difficulty breathing?
ln the last week, have you had new vomiting?
U ono
tr l,Yes
ln the last week, have you had new diarrhea (multiple watary stools)?
lnths last week, have you had a nsw lo*e of smellor t.st6?
lndicste when you have lost yaur eense sf rmall, teste, or botlr"
Did you receive the influenza veccin* this past season?
ln the last week, have you received c€re or bean tasted
for coronavirus in sn office or clinic?
What diagnosis (or diagnoses) were you given?
0, No
1, Yes
2, I don't know
0, No
t, Yes
1, I felt feverish but did not take my
tamperature.
untr
nn
tr
0, No
I", Yoa
2,ldon'tknow
n o,No
n 
l,Yas
n o,No
n l,Yeo
n qno
n x,, Yes
tr 0,Srnall
n l,Teuta
n 
2, Brrth rmellandtasta
u
n
tr
0,llo
1, Yei, for ons or mors of the ebnve symptomc
2, Yae, for snother ro{ion


Name of emergency contact:
Relationship of emergency contact:
n $ SpoumlPartner
n ,., child
n Z,Parent
tr 3,Sibling
tr 4,6randparant
n 5,Aunt
n 6, Uncla
tr 7, Courin
tr 8, Unrelated Adult/Roornmrte
EI 9, Friend
n 
1Q Naighbor
n 
11, Othar {specrfy below}
Mobile phone number of emergency contact:
Name sf stscond emergency contact:
fielationship of second emerE€ncy contact:
tr Q$pou*rlFrrtner
tr r, child
n 
?, Parant
n 
3, Sibling
tr dGrandp*rsnt
tr S,Aunt
tr I uncle
tr 7, Cousin
n 
8, Unrelated Aduh/fiaommate
n 
9, Frisnd
n 
lO, Naighbor
n 
11" 0ther (spacify below)
PaSs 7 of ll8


I 
fvfoUlte phone number af second emergency contact:
How would you describe your ethnicity?
How would you describe your race?
tr 1, Hispanlc, Latino, Latina, sr Latinx
E 2. Middle fastern or North African descent
tl 
S. NEnaoftheabove
tr 3,Prefernottoreport
n 
1, Arnerican lndian orAlaskan Native
El 2, Asian
tr 3, Black or African American
n 4, First Nations, lnuit, or Mdtis
n 5, Native Hawaiian or other Pacific lslander
n o, white
n 6, Other
tl 
7, Prefernotto report


Appendix O
Day:
Updete on how you are feellng
ln tha last day, have you had a new fever > 10O" F?
ln the last dry, hava you had a nelv cough?
n o,No
tl 
1, Yes
ln the last day, have you felt new shortness of breath or had new difficulty breathing?
ln tha last day, have you had new vorniting?
0, No
tr l,Ys*
ln tho laat day, have you had new diarrhea {multiple watery stoo}r}?
ln ths hEt dry, hava you hsd . reur lors of Emdl or te*ts?
lndicate whan you hava lost yo{rr ssnse of smell, taste, or both.
ln the laEt day, have you had eny additional rymptoms?
ln the la$ day, have $,u tekrn eny naw medicrtions?
lf *o plaase list bslow
4No
1, Yes
1, I felt feverirh but did not trke my
tsrmperahrra.
tr
n
0, No
l, Yas
n
tr
tr
n
n
tr
tr
tr
n
n
tr
0, No
1, Yes
0, No
1, Yes
0,Smell
1, Taste
2, Both smell and taste
0, No
1, Yes
0, No
L, Yes
CINJ 002011 COVID-19 Follow-up Questionnaire
Patlent:
tr
n
tr
Page 9 of48


In the last day, lravr you rec*iva car6 or hed tasts in an
offlce orclinic?
Dacumsnt hst or procadur*s
n
ONs
1, Yes
Plessa provide all temperatures
recorded on your log in the last
24 hours.
AM:
Mid-dny
Aftarnoun:
Night:
ln tha last day, hava you taken your study medication
as prescribed?
ONo
1, Yes
Page 10 of 68