Clinical trial NCT04372017
Conditions: COVID-19 SARS-CoV 2
Sponsor: Sanford Health
Start date: 2020-05-14; Completion date: 2021-06-04
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a prospective, double-blind, randomized, placebo-controlled study in two distinct cohorts to evaluate the efficacy and safety of hydroxychloroquine in the prevention of COVID-19 infection.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None arm 4: None
Interventions: intervention 1: Hydroxychloroquine intervention 2: Vitamin D
Intervention descriptions: intervention 1: Participants randomized to hydroxychloroquine will take 800mg on day 1 followed by 400mg on days 2-5. intervention 2: Participants randomized to placebo will take IU1600 on day 1 and IU 800 on days 2-5.

Protocol documents:
Prot_SAP_002.pdf: 
Hydroxychloroquine as Post-Exposure 
Prophylaxis Against COVID-19 Infection 
(PEPCOH) 
 
 
 
NCT04372017 
 
 
Protocol Document including SAP 
 
Continuing Review Date 03.11.2021 


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Protocol Title 
Post-Exposure Prophylaxis for COVID-19 with 
Hydroxychloroquine  
 
 
Protocol Number:  PEPCOH 
Lead site Name:  Sanford Health  
 
Study Chair:  Susan Hoover, MD   
 
Version:  1.0   (2020.05.15) 
 
NCT: 04372017 
 
 
 


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Responsibility Acknowledgement:  
I have read this study protocol and agree to adhere to the requirements.  I will provide copies of 
this study protocol and all pertinent information to the study personnel.  I will discuss this 
material with them and ensure they are fully informed regarding the study interventions and the 
conduct of the study according to the Food and Drug Administration (FDA) Guidelines for Good 
Clinical Practices (GCP), the institutional policies and procedures, and pertinent individual 
country laws/regulations. 
 
 
 
Site Principal Investigator 
 
Date 
 
 
 
 


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Table of Contents 
1.0 
Protocol Summary ............................................................................................................................ 6 
1.1 
Synopsis ........................................................................................................................................ 6 
1.2 
Schema .......................................................................................................................................... 9 
1.3 
Schedule of Activities (SoA) Cohort A & B ............................................................................... 10 
2.0 
Introduction ..................................................................................................................................... 11 
2.1 
Study Rationale ........................................................................................................................... 11 
2.2 
Background ................................................................................................................................. 11 
3.0 
Objectives and Endpoints................................................................................................................ 11 
3.1 
Primary Objectives ...................................................................................................................... 11 
3.2 
Primary Hypothesis: .................................................................................................................... 11 
4.0 
Study Design ................................................................................................................................... 12 
4.1 
Overall study design ................................................................................................................... 12 
4.2 
End of Study Definition .............................................................................................................. 12 
5.0 
Study Population ............................................................................................................................. 12 
5.1 
Inclusion Criteria ........................................................................................................................ 12 
5.2 
Exclusion..................................................................................................................................... 12 
5.2 
Screen Failures ............................................................................................................................ 12 
6.0 
Study Intervention ........................................................................................................................... 12 
6.1 
Study Intervention(s) Administered: ........................................................................................... 12 
6.2 
Hydroxychloroquine Sulfate (See Appendix C for more information) ....................................... 13 
6.3 
Vitamin D with calcium (Cholecalciferol) .................................................................................. 16 
6.4 
Participant Implications .............................................................................................................. 17 
6.5 
Drug Inventory Records .............................................................................................................. 18 
6.6 
Measures to Minimize Bias: Randomization and Blinding ........................................................ 18 
6.7 
Study Intervention Compliance .................................................................................................. 18 
6.8 
Concomitant Therapy .................................................................................................................. 18 
6.9 
Intervention after the End of the Study ....................................................................................... 18 
7.0 
Participant Discontinuation/Withdrawal ......................................................................................... 18 


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7.1 
Discontinuation of Study Intervention: ....................................................................................... 19 
7.2 
Participant Withdrawal from the Study ...................................................................................... 19 
7.3 
Lost To Follow Up ...................................................................................................................... 19 
8.0 
Study Procedures and Safety Assessments ..................................................................................... 20 
8.1 
Administrative Procedures .......................................................................................................... 20 
8.1.1 
Screening Procedures .......................................................................................................... 20 
8.1.2 
Informed Consent ................................................................................................................ 20 
8.1.3 
Inclusion/Exclusion Criteria ............................................................................................... 21 
8.1.4 
Assignment of Screening Number ...................................................................................... 21 
8.1.5 
Enrollment ........................................................................................................................... 21 
8.1.6 
Assignment of Study Participant Number........................................................................... 21 
8.2 
Clinical Procedures/Assessments ................................................................................................ 21 
8.2.1 
Participant Reported Outcomes .......................................................................................... 21 
8.2.2 
Adverse Event (AE) Monitoring ......................................................................................... 22 
8.3 
Adverse events and Serious Adverse Events: ............................................................................. 22 
8.3.1 
AE and SAE Collection and Reporting ............................................................................... 23 
8.3.2 
AE/SAE Assessments ......................................................................................................... 23 
8.3.3 
Safety Review Committee (SRC) ....................................................................................... 24 
9.0 
Statistical Considerations ................................................................................................................ 24 
9.1 
Statistical Hypothesis .................................................................................................................. 24 
9.2 
Sample Size Determination ......................................................................................................... 24 
9.3 
Statistical Analyses ..................................................................................................................... 25 
9.4 
Interim Analysis .......................................................................................................................... 25 
10.0 
Regulatory, Ethical, and Study Oversight ....................................................................................... 26 
10.1 
Statement of Compliance ............................................................................................................ 26 
10.2 
Informed Consent ........................................................................................................................ 26 
10.3 
Study Participant Confidentiality ................................................................................................ 27 
10.4 
Risks and Benefits ....................................................................................................................... 27 
10.5 
Ethics........................................................................................................................................... 27 


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10.6 
Study Documentation and Case Report Forms (CRFs) .............................................................. 27 
10.7 
Document and Data Retention .................................................................................................... 28 
10.8 
Direct Access to Source Data/Documents .................................................................................. 28 
10.9 
Protocol Compliance ................................................................................................................... 28 
10.10 Publication Policy ....................................................................................................................... 28 
Appendix A: Abbreviations ........................................................................................................................ 29 
Appendix B:  Protocol Amendment History ............................................................................................... 30 
Appendix C:  Hydroxychloroquine Drug Information................................................................................ 31 
Appendix D:  Exclusion Medication List ................................................................................................... 33 
Appendix E: References ............................................................................................................................. 50 
 
 
 


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1.0 
Protocol Summary 
1.1 
Synopsis 
Title of Study 
Post-Exposure Prophylaxis for COVID-19 with Hydroxychloroquine 
(PEPCOH) 
 
Study Objectives 
Primary:  
 
Cohort A: Determine whether post-exposure prophylaxis with hydroxychloroquine 
can prevent COVID-19 in healthcare workers who have been exposed to a known 
case of COVID-19. 
 
Cohort B: Determine whether post-exposure prophylaxis with hydroxychloroquine 
can prevent COVID-19 in high-risk individuals who have been exposed to a known 
case of COVID-19. 
Primary Hypothesis: 
 
Cohort A: Primary Hypothesis:  Hydroxychloroquine will reduce the number of 
healthcare workers that convert to infected status post-exposure compared with 
placebo. 
 
Cohort B:  Primary Hypothesis: Hydroxychloroquine will reduce the number of 
high-risk individuals that convert to infected status post-exposure compared with 
placebo. 
Study Design 
A multi-cohort, prospective, double-blind, randomized, placebo controlled study  
Study 
Population 
Inclusion Criteria: 
Inclusion Criteria Cohort A: 
 
≥ 18 years old 
 
Employee of healthcare organization in South Dakota or  Sanford Health employee in 
any location and with exposure to a person with COVID-19 within the last 5 days 
o 
Occupational exposure as determined by the participant’s  employee health 
department (i.e. not wearing the proper Personal Protective Equipment (PPE)) 
o 
Criteria according to Center for Disease Control (CDC) guidelines 
o 
Community exposure (within 6 feet for at least 15 minutes) 
 
No current symptoms attributable to COVID-19, per HCW report (fever, cough, 
difficulty breathing, sore throat)  
 
No prior COVID-19 positive diagnosis (eligible if previous testing is negative and meets 
all other inclusion and exclusion) 
 
Ability to provide informed consent 
 
 
Inclusion Criteria – Cohort B 
 
≥ 18 years old  
 
High-risk person who had close contact (i.e. within 6 feet for at least 15 minutes) with a 
COVID-19 positive person within the last 5 days and is a South Dakota resident or high-
risk person with close household contact of a COVID-19 positive Sanford employee  


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 
High-risk person defined by: 
 
Age 18-44 with 2 or more comorbidities listed below 
 
Age 45-79 with any comorbid condition listed below 
 
Age 80 and above (regardless of comorbid conditions) 
 
Co-morbid list 
o 
Congestive Heart Failure (CHF)  
o 
Chronic lung disease¥  
o 
Solid organ transplant or immunosuppression*  
o 
Chronic Kidney Disease or End Stage Renal Disease  
o 
Diabetes mellitus     
o 
Cardiovascular disease/Hypertension  
o 
Smoking/Vaping (currently using or history of using in the past 1 year) 
o 
Obesity  (calculated by height and weight per participant report)  
o 
Hyperlipidemia 
¥ Includes any of the following: asthma, chronic obstructive pulmonary disease, 
emphysema 
* Defined as an outpatient prescription of greater than 10 mg/day of prednisone 
or equivalent, use of chemotherapy, or use of immunosuppressive agents for 
solid organ transplant or for an autoimmune disease.  
 
No current symptoms attributable to COVID-19 
 
No prior COVID-19 positive diagnosis (eligible if previous testing is negative and meets 
all other inclusion and exclusion) 
 
Ability to provide informed consent 
 
Confirmed review of concomitant medications (with emphasis on cardiac medications) 
 
Exclusion Criteria: 
  Exclusion Criteria Cohort A & B: 
 
Known allergy to hydroxychloroquine or quinine 
 
Known history of long QT syndrome 
 
Known history of arrhythmia or dysrhythmia  
 
Known current QTc >500 ms 
 
Known G6PD deficiency 
 
Known history of hypoglycemia 
 
Pregnant or Nursing by patient history 
 
Use of any of the following concomitant medications: See Appendix D for Exclusion 
medication list  
 
Concurrent diagnosis of dermatitis, porphyria, or psoriasis 
 
History of chronic liver disease, including cirrhosis and/or diagnosis of hepatitis 
(infectious, idiopathic, or immune) 
 
History of chronic kidney disease 
 
Pre-existing retinopathy 
 
Already taking hydroxychloroquine 
 
Any condition or medication in the opinion of the investigator that would prohibit the use 
of hydroxychloroquine 
 
Enrollment in another clinical with investigational drug or device 
 
Inability to swallow pills 
 
Adults unable to provide informed consent 
 


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Sample Size 
Cohort A  n= 1356 
Cohort B  n= 383 
Study 
Intervention 
Hydroxychloroquine vs. Placebo (Vitamin D with calcium) 
Study 
Evaluations 
Assessments on this study will be completed as outlined in Section 8.3. 
Study Period 
Planned start date: April 2020 
Planned accrual start date: April 2020  
Planned accrual closure:  April 2021 
Planned study closure: April 2022 
 
 
 


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1.2 
Schema 
 


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1.3 
Schedule of Activities (SoA) Cohort A & B 
This study consists of screening, enrollment and randomization, treatment, and follow-up.  Follow-up will include evaluation of the treatment and 
subsequent infection, re-infection, adverse events, and long-term sequelae of treatment and/or infection. The detailed schedule of study procedures 
and assessments with the time intervals is shown in Table 1. 
Table 1 
 
Screening & Enrollment 
Treatment / Placebo Phase 
Follow-upb 
Procedure 
Screeninga 
Enrollment / 
Randomization 
Day 1 
Day 2 
Day 3f 
Day 4 
Day 5 
Day 14 
(+ 1 day) 
Day 35e 
(+3 days) 
12 Months 
(+30 days) 
Informed Consent / 
HIPAA 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
Hydroxychloroquine / 
Placebo (Vitamin D with 
calcium) 
 
 
X 
X 
X 
X 
X 
 
 
 
Patient Reported 
symptomsc 
 
 
 
 
X 
 
X 
X 
X 
 
Adverse Event 
Assessment 
 
 
 
 
X 
 
X 
X 
X 
X 
Outcomesd 
 
 
 
 
 
 
 
X 
X 
X 
a. Screening must be completed within 48 hours prior to study enrollment 
b. Follow-up visits will consist of a phone call to the patient. Hydroxychloroquine and placebo patients will be followed. 
c. Includes: patient reported temperature, cough, difficulty breathing, sore throat, chills, muscle pain, headache, new loss of taste or smell, and diarrhea. 
d. Did the patient acquire COVID-19? 
e. Day 35 should be at least 30 days (+3 days) post last dose of drug. 
f. Day 3 and 5 AE assessment via phone call. (window +1day) 


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2.0 
Introduction  
2.1 
Study Rationale 
Currently, prevention of person-to-person transmission of SARS-CoV-2, the virus 
which causes COVID-19, is achieved by reducing close contact through physical 
distancing measures and through the use of personal protective equipment (PPE) in 
the healthcare setting. The effect of post-exposure medication treatment on 
acquisition of infection or progression to symptomatic disease is unknown. 
2.2 
Background 
Coronavirus Infectious Disease-2019 (COVID-19) is an infection caused by a novel 
virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which 
emerged in the winter of 2019 initially in China, then spread to involve the entire 
world in a pandemic. Infected individuals may be asymptomatic, while others 
demonstrate a range of symptoms from upper respiratory symptoms to pneumonia, 
respiratory failure, acute respiratory distress syndrome, or death.  
Hydroxychloroquine inhibits SARS-CoV-2 replication in vitro and may have antiviral 
effects in people with COVID-19 disease (Yao et al. 2020).  It is postulated that early 
preemptive therapy may prevent disease or reduce severity, but its effectiveness in the 
post-exposure setting is unknown. 
3.0 
Objectives and Endpoints  
3.1 
Primary Objectives 
 
Cohort A: Determine whether post-exposure prophylaxis with 
hydroxychloroquine can prevent COVID-19 in healthcare workers with direct 
patient contact who have been exposed to a known case of COVID-19. 
 
Cohort B: Determine whether post-exposure prophylaxis with hydroxychloroquine 
can prevent COVID-19 in high-risk individuals who have been exposed to a 
known case of COVID-19. 
  
 
3.2 
Primary Hypothesis: 
 
Cohort A: Primary Hypothesis:  Hydroxychloroquine will reduce the number of 
healthcare workers that convert to infected status post-exposure compared with 
placebo. 
 
Cohort B:  Primary Hypothesis: Hydroxychloroquine will reduce the number of 
high-risk individuals that convert to infected status post-exposure compared with 
placebo. 


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4.0 
Study Design  
4.1 
Overall study design 
This is a prospective, double-blind, randomized, placebo-controlled study in two 
distinct cohorts to evaluate the efficacy and safety of hydroxychloroquine in the 
prevention of COVID-19 infection.  Additional sub-studies will be added and 
removed throughout this larger “tent” protocol to answer other objectives.  These 
studies will be listed in the appendices of this protocol. 
Other non-Sanford institutions will be allowed to participate in this study after all 
legal and regulatory documents are final. 
Sanford Health will function as the lead site for trial oversight.  
4.2 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all 
phases of the study including last follow up visit at 12 months. 
5.0 
Study Population 
5.1 
Inclusion Criteria 
 
 
See Synopsis (section 1.1) 
 
5.2 
Exclusion 
 
 
See Synopsis (section 1.1) 
5.2 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical 
study but are not subsequently enrolled. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants.  Minimal 
information should include demography, screen failure details, eligibility criteria, and 
any serious adverse event (SAE). Screen failures will not count towards total 
enrollment. 
6.0 
Study Intervention 
 
6.1 
Study Intervention(s) Administered:  
Hydroxychloroquine/placebo (vitamin D with calcium) will be administered as part of 
this study. Randomization will occur at a 1:1 ratio in each cohort. Participation in 
additional non-interventional clinical research studies is allowed.  If the participant 
becomes infected with COVID-19, the participant will stop the intervention and be 
treated per the discretion of their primary care provider.  
 


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Subjects enrolled will be assigned to the appropriate cohort and randomized to receive 
hydroxychloroquine 200mg tablets, Day 1 – 2 tablets by mouth twice per day, Day 2-
5 1 tablet by mouth twice per day (total of 12 tablets) or placebo. Placebo will be 
vitamin D with calcium tablets 10mcg tablet - Day 1 – 2 tablets by mouth twice per 
day, Day 2-5 1 tablet by mouth twice per day (total of 12 tablets). Subjects will be 
monitored for any toxicities during and after treatment.   
 Table 2. Intervention dosing 
 
6.2 
Hydroxychloroquine Sulfate (See Appendix C for more information) 
6.2.1. 
Other Names 
 
IUPAC: 2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-
ethylamino]ethanol 
MeSH: Plaquenil; Hydroxychlorochin; Hydroxychloroquine; 
Hydroxychloroquine Sulfate: Hydroxychloroquine Sulfate (1:1) Salt; 
Oxychlorochin; Oxychloroquin; 4-aminoquinoline 
 
6.2.2. 
Classification 
Immunosuppressive, anti-inflammatory, anti-autophagy, and anti-
malarial 
 
6.2.3. 
Dose Specifics 
One tablet of 200 mg of hydroxychloroquine sulfate is equivalent to 
155 mg base.  See section 6.1 for dosing. 
 
 
6.2.5. 
Preparation 
No special preparation.    
 
6.2.6. 
Administration 
Take hydroxychloroquine sulfate by mouth, preferably with a meal or 
a glass of milk. 
 
6.2.7. 
Contraindications 
Use of hydroxychloroquine sulfate is contraindicated in patients with 
known hypersensitivity to 4-aminoquinoline compounds. Use with 
Drug 
Dose 
Dose Frequency 
Route 
Hydroxychloroquine 
200 mg tablets 
2 tablets 
Twice daily on day 1 
PO 
1 tablet 
Twice daily on days 2-5 
PO 
Placebo (vitamin D 
with calcium, 
10mcg/25mg tablets) 
2 tablets 
Twice daily on day 1 
PO 
1 tablet 
Twice daily on days 2-5 
PO 


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caution in patients with alcoholism, hepatic/renal dysfunction, glucose-
6-phosphate dehydrogenase (G-6-PD) deficiency, gastrointestinal, 
neurological, or blood disorders. A dose reduction may be required. 
 
6.2.8. 
Availability 
Commercially available as a tablet for oral administration.  For the 
purposes of this study the tablet drug will be provided by Sanford 
Research and supplied in 200mg tablets with matching placebo. 
 
6.2.9. 
Side Effects 
 
1. Ocular:  
It is recommended that hydroxychloroquine be discontinued if 
ocular toxicity is suspected and the patient should be closely 
observed given that retinal changes (and visual disturbances) may 
progress even after cessation of therapy. 
 
Retinal toxicity from hydroxychloroquine is serious but very rare. 
The incidence rises sharply to about 1% at 5 years of use, so 
the American Academy of Ophthalmology recommends screening 
starting after 5 years. Toxicity is more common with doses 
exceeding 400 mg/day or a total dose of more than 1000 g.  This 
study dose is 800 mg for 1 day then 400 mg for 4 more days 
(Marmor et al. 2011). 
 
2. Cardiac: Post marketing cases of life-threatening and fatal 
cardiomyopathy have been reported with use of 
hydroxychloroquine sulfate. Patients may present with 
atrioventricular block, pulmonary hypertension, and sick sinus 
syndrome or with cardiac complications. Electrocardiogram (ECG) 
findings may include atrioventricular, right or left bundle branch 
block. Signs or symptoms of cardiac compromise have appeared 
during acute and chronic treatment. Clinical monitoring for signs 
and symptoms of cardiomyopathy is advised. Chronic toxicity 
should be considered when conduction disorders (bundle branch 
block/atrio-ventricular heart block) or biventricular hypertrophy are 
diagnosed. If cardiotoxicity is suspected, prompt discontinuation of 
hydroxychloroquine sulfate may prevent life-threatening 
complications. 
 
Hydroxychloroquine sulfate prolongs the QT interval. Ventricular 
arrhythmias and torsades de pointes have been reported in patients 
taking hydroxychloroquine. Therefore, hydroxychloroquine sulfate 
should not be administered with other drugs that have the potential 
to prolong the QT interval. 


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Hydroxychloroquine has been used for decades for malaria and 
autoimmune disease without pre-treatment EKGs or routine cardiac 
monitoring. A 2018 review of short-term antimalarial treatment 
including chloroquine, which is known to carry greater risk of 
toxicity, found no serious cardiac adverse events among 
participants (n=1076), receiving acute therapy for malaria. With 
chronic use of hydroxychloroquine (years), QT prolongation and 
cardiomyopathy have occurred. This study uses a 5-day course and 
subjects with heart disease will be excluded (Haeusler et al. 2018). 
 
3. Worsening of Psoriasis and Porphyria: Use of hydroxychloroquine 
sulfate in patients with psoriasis may precipitate a severe attack of 
psoriasis. When used in patients with porphyria the condition may 
be exacerbated. The preparation should not be used in these 
conditions unless in the judgment of the physician the benefit to the 
patient outweighs the possible hazard. 
 
4. Proximal Myopathy and Neuropathy: Skeletal muscle myopathy or 
neuropathy leading to progressive weakness and atrophy of 
proximal muscle groups, depressed tendon reflexes, and abnormal 
nerve conduction, have been reported. Muscle and nerve biopsies 
have been associated with curvilinear bodies and muscle fiber 
atrophy with vacuolar changes. Assess muscle strength and deep 
tendon reflexes periodically in patients on long-term therapy with 
hydroxychloroquine sulfate. 
 
5. Neuropsychiatric Events, Including Suicidality: Suicidal behavior 
has been rarely reported in patients treated with 
hydroxychloroquine sulfate. 
 
6. Hypoglycemia: Hydroxychloroquine sulfate has been shown to 
cause severe hypoglycemia including loss of consciousness that 
could be life threatening in patients treated with or without 
antidiabetic medications.  Patients treated with hydroxychloroquine 
sulfate should be warned about the risk of hypoglycemia and the 
associated clinical signs and symptoms. Patients presenting with 
clinical symptoms suggestive of hypoglycemia during treatment 
with hydroxychloroquine sulfate should have their blood glucose 
checked and treatment reviewed as necessary. 
 
7. Dermatologic Effects: Dermatologic reactions to 
hydroxychloroquine sulfate may occur and, therefore, proper care 
should be exercised when it is administered to any patient receiving 
a drug with a significant tendency to produce dermatitis.  


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6.3 
Vitamin D with calcium (Cholecalciferol) 
6.3.1 
Other Names IUPAC Name: (1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-7a-
methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-
inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol 
MeSH: (3 beta,5Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3-ol; 
Calciol; Cholecalciferol; Vitamin D3 
6.3.2 
Classification Lipophilic secosteroid 
6.3.3 
Mode of Action 
 
Vitamin D with calcium is dietary supplement used to promote calcium 
absorption in intestines, bone resorption, increase phosphate levels to 
maintain skeletal calcium balance. In vivo synthesis of the major 
biologically active metabolites of vitamin D with calcium occurs in 
two steps. First, in the liver microsomal enzymes convert vitamin D to 
calcifediol (25-hydroxycholecalciferol).  Second, calcifediol is released 
into  systemic circulation where it binds vitamin D-binding protein, an 
α-globulin carrier protein that transports it to the proximal tubules of 
the kidneys where Parathyroid hormone  regulates its further 
hydroxylation to  calcitriol (1,25-dihydroxycholecalciferol). Calcitriol 
is again released into systemic circulation, binds to vitamin D-binding 
protein and is distributed to throughout the body including to target 
organs like intestine, kidney, and bone. Vitamin D is indicated in 
treatment of hypoparathyroidism, refractory rickets, and familial 
hypophosphatemia. 
Vitamin D3 and vitamin D2 are bioequivalent. 
 
6.3.4 
Storage and Stability 
 
Vitamin D3 with calcium tablets are stored at room temperature 15°-
30°C (59°-86°F), protect from light and moisture. They should be 
dispense in a tight, light-resistant container.  
6.3.5 
Dose Specifics 
 
Placebo will be vitamin D with calcium tablets 10mcg/25mg tablet.  
See section 6.1 for dosing. 
6.3.6 
Preparation  
No special preparation.   
6.3.7 
Administration 
 
Take Vitamin D3 with calcium by mouth with meal or a glass of milk. 
Take hydroxychloroquine sulfate by mouth, preferably with a meal or 
a glass of milk. 


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6.3.8 
Contraindications: 
 
Use of Vitamin D3 with calcium is contraindicated in patients with 
renal impairment, heart disease, kidney stones, arteriosclerosis, and  
individuals with hypercalcemia, hypervitaminosis D; gastrointestinal, 
liver, or biliary disease associated with malabsorption of vitamin D 
analogues and drugs that could have allergenic cross 
reactivity/hypersensitivity with Vitamin D3.  
6.3.9 
Availability 
Commercially available as a tablet for oral administration.  For the 
purposes of this study the tablet drug will be provided by Sanford 
Research and supplied in 10mcg/25mg tablets as placebo. 
. 
6.3.10 
Side Effects 
1. Renal: Impairment of renal function with polyuria, nocturia, 
polydipsia, hypercalcemia, reversible azotemia, hypertension, 
nephrocalcinosis, generalized vascular calcification, or irreversible 
renal insufficiency which may result in death 
2. Central Nervous System (CNS): Mental retardation, disorientation, 
confusion 
3. Soft Tissues: widespread calcification of the soft tissues, including 
the heart, blood vessels, renal tubules, and lungs 
4. Skeletal: Bone demineralization (osteoporosis) in adults. Decline in 
the average rate of linear growth and increased mineralization of 
bones in infants and children (dwarfism), vague aches, stiffness, 
and weakness 
5. Gastrointestinal: Nausea, anorexia, and constipation 
6. Metabolic: Mild acidosis, anemia, and weight loss 
7. Teratogenic effects: supravalvular aortic stenosis, elfin facies, and 
mental retardation recorded in pregnant women with 
hypervitaminosis D 
6.4 
Participant Implications 
1. If a participant vomits after taking their dose study drug it will be 
considered a missed dose and not retaken.  The participant will resume 
with the next scheduled dose. 
2. If the participant forgets to take a dose, that dose will not be made up and 
participant will resume with the next scheduled dose. 
3. If the participant is unable to start the hydroxycholoroquine / vitamin D 
with calcium in the morning on Day 1 due to delivery timing, the 
participant is allowed to initiate Day 1 with an evening dose. 
4. Participants should have at least 8 hours between doses. 


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5. Participants will be instructed to inform the study coordinator of any 
medication changes while on the active phase of the study 
6.5 
Drug Inventory Records 
Investigational Product Records at Investigational Site(s): It is the 
responsibility of the Investigator to ensure that a current record of 
investigational product disposition is maintained at each study site where 
investigational product is inventoried and disposed. 
6.6 
Measures to Minimize Bias: Randomization and Blinding 
On enrollment day, the participant will be assigned a unique number 
(randomization number). The randomization number encodes the participant’s 
assignment to hydroxychloroquine or placebo (vitamin D with calcium), 
according to the randomization schedule generated prior to the study by the 
Sanford Command Core. Each participant will be dispensed randomized study 
intervention, labeled with his/her unique randomization number, throughout 
the study. 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access 
to study intervention records at the site(s) to verify that 
randomization/dispensing has been done accurately. 
6.7 
Study Intervention Compliance 
 
A pill diary will be given to each enrolled participant to document pill 
 
compliance.  
6.8 
Concomitant Therapy 
 See inclusion and exclusion criteria for medications that are not allowed. 
 No washout period is needed for hydroxychloroquine. 
 Vaccines are allowed while on the study. 
6.9 
Intervention after the End of the Study 
Participants who acquire COVID-19 while on study intervention as 
determined by a positive test indicating COVID-19 will be instructed to 
discontinue the study intervention by the study team. Participants will be 
unblinded and subsequent treatment will be at the discretion of their primary 
care physician or provider who ordered the COVID-19 testing.  
 
7.0 
Participant Discontinuation/Withdrawal 
Participants may withdraw consent at any time for any reason or be withdrawn from 
the trial at the discretion of the investigator should any untoward effect occur.  In 
addition, a participant may be withdrawn by the investigator if enrollment into the 
trial is inappropriate, the trial plan is violated, or for administrative and/or other safety 
reasons.  


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7.1 
Discontinuation of Study Intervention:  
A participant must be discontinued from the trial for any of the following 
 
reasons: 
 The participant withdraws consent. 
 Intercurrent illness that prevents further administration of treatment 
 The participant has a confirmed positive pregnancy test 
 The participant is lost to follow-up 
At the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
 
For those participants who discontinue study intervention early, each participant 
will be followed for 30 days for acute adverse event monitoring.   
7.2 
Participant Withdrawal from the Study 
 A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, compliance, or administrative reasons. 
 If the participant withdraws consent for disclosure of future information, any 
data collected be for that time may be retained. 
 
7.3 
Lost To Follow Up   
All reasonable efforts must be made to locate participants to determine and report 
 
their ongoing status.  This includes follow-up with persons authorized by the 
 
participant.   
Lost to follow-up is defined by: 
 The inability to reach the participant after a minimum of two documented 
phone calls and 
 Lack of response by participant to one certified mail letter.   
All attempts should be documented in the participant medical record.  Should the 
participant continue to be unreachable, he/she will be considered lost to follow up. 
Outcome information that is available via electronic medical records will be 
documented if available. 
If it is determined that the participant has died, the site will use permissible local 
methods to obtain the date and cause of death. 
 


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8.0 
Study Procedures and Safety Assessments  
8.1 
Administrative Procedures 
 
8.1.1 Screening Procedures 
All participants must agree to participate in the study prior to any study 
specific screening procedures being performed.  Every participant shall be 
provided an Institutional Review Board (IRB)-approved informed consent to 
review and keep for his/her records.   
Once consent has been documented, the site will assign the participant a 
screening number.  A Screening Log of consented patients will be maintained 
at each site. 
Screening evaluations will be used to determine the eligibility of the 
participant for study inclusion.  All screening activities must be completed 
within 48 hours prior to study enrollment and include the following: 
 Inclusion/Exclusion Criteria 
 Demographics and Medical History  
All screening evaluations must be completed and reviewed by the site 
investigator or healthcare licensed designee to confirm that potential 
participants meet all eligibility criteria. The study team will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.  
8.1.2 Informed Consent 
A study team member must obtain documented consent from each potential 
participant prior to participating in a clinical trial. This study will utilize an 
electronic consent process based in REDCap, a CFR part 11 compliant 
research database.  An electronic version of the informed consent form will be 
approved by the IRB prior to use.  When a participant is contacted for 
enrollment into the study, an email containing a unique link will be generated 
by REDCap and sent to the patient while on the phone with a study team 
member.  A password will be provided to the participant verbally over the 
phone that is required to access the informed consent.  This provides 
confirmation of the identity of the participant.  Once the informed consent 
form has successfully accessed, the study team member will allow a period of 
time of 1-4 hours for the participant to read the informed consent and 
formulate questions.  The study team member will place another call with the 
participant and proceed to have an informed consent discussion, answering 
any questions the participant might have.  If the participant is willing to 
participate in the study, he or she will proceed to provide an electronic 
signature using a mouse or their finger and save the document.  This locks the 
document from any further changes.  An email containing a copy of the signed 
informed consent form will be generated via REDCap and emailed to the 
participant.  A PDF of the signed informed consent document will be saved in 
the participant’s medical record as well as printed out for the study file.   


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A copy of the consent form will be automatically generated via REDCap and 
emailed to the participant before participation in the trial.  The research team 
member who obtained consent will record the consenting process per their 
institutional guidelines.  
The initial informed consent form, any subsequent revised written informed 
consent form and any written information provided to the participant must 
receive the IRB’s approval in advance of use.  The participant will be 
informed in a timely manner if new information becomes available that may 
be relevant to the participant’s willingness to continue participation in the trial.  
The informed consent will adhere to IRB requirements, applicable laws and 
regulations. 
8.1.3 Inclusion/Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed by the site Principal 
Investigator (PI) or licensed designee to ensure that the participant qualifies 
for the study. 
8.1.4 Assignment of Screening Number 
Consented participants will be assigned a screening number.  
8.1.5 Enrollment 
Once all screening procedures have been completed the site PI or licensed 
designee (RN, CNP, pharmacist, or physician) on the study team will 
review acknowledge the inclusion/exclusion source document. If the potential 
participant is determined to be eligible, the study site will enroll the participant 
in appropriate cohort in the electronic data capture (EDC) and then 
randomized by the Sanford Command Core to the intervention assignment. 
Sites will be notified by email in real time the randomization confirmation.  
The site study team will maintain an enrollment log and the lead site will 
maintain a study-wide enrollment log. If the potential participant is not eligible 
and becomes a screen fail, the reason will be noted on the inclusion/exclusion 
in the EDC and filed in the study records. 
 
8.1.6 Assignment of Study Participant Number 
Participants will be assigned a participant study number at enrollment at the 
same time as randomization by the EDC.  This number will be unique to this 
participant.  
8.2 
Clinical Procedures/Assessments   
See Schedule of events for activities that need to be done at each visit. 
8.2.1 Participant Reported Outcomes 
Participant self-reported COVID-19 symptoms (temperature, cough, difficulty 
breathing, and sore throat) will be collected by the study team at time points 
outlined in the SoA. Participants will also be asked if they have or are 


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currently experiencing any other symptoms since starting the study 
intervention.  These will be included in the adverse event monitoring. 
8.2.2 Adverse Event (AE) Monitoring 
The investigator or licensed designee (RN, CNP, pharmacist, or physician) 
on the study team will assess each participant to evaluate for potential new or 
worsening AEs as specified in the SoA and more frequently if clinically 
indicated.  If participant reported symptoms are an AE, the event will be 
tracked as an AE.   
Participants will be followed and accessed for acute AEs until day 35 (30 days 
after the last dose of study medication).  AEs will be documented accordingly. 
Adverse events will also be assessed at the 12 month follow up visit. 
8.3 
Adverse events and Serious Adverse Events (SAE):  
An AE is defined as any untoward or unfavorable medical occurrence in 
human participants, including any abnormal sign, symptom, or disease, 
temporally associated with the participant’s participation in the research, 
whether considered related to the participant’s participation in the research or 
not. AEs encompass both physical, psychological harms, and biochemical 
abnormalities. AEs may be reported by the participant, observed by the 
Investigator, or documented in medical records. 
The site investigator and any licensed designees are responsible for detecting, 
documenting, and recording events that meet the definition of an AE or SAE 
and remain responsible for following up AEs that are serious, considered 
related to the study intervention or study procedures, or that caused the 
participant to discontinue the study treatment. The site investigator or licensed 
designee will evaluate all adverse events according to the National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5.0.  Toxicities will be characterized in terms regarding grade 
(seriousness), causality/attribution (see section 8.3.2), and action taken with 
regard to trial intervention.  
Any adverse event which changes CTCAE grade over the course of a given 
episode will have each change of grade recorded on the adverse event case 
report forms/worksheets.  
If the adverse event meets any of the criteria below, it is regarded as a SAE:  
 the event led to the death of the participant  
 the event led to serious deterioration in the health of the participant, 
that either resulted in:  
o a life-threatening illness or injury 
o a permanent impairment of a body structure or a body function 
o in-patient or prolonged hospitalization  


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 an important medical event- defined as an event requiring medical or 
surgical intervention to prevent one of the outcomes listed above in 
this definition. 
8.3.1 AE and SAE Collection and Reporting  
All acute SAEs/AEs will be collected from the time the informed consent form 
(ICF) is signed until day 35.  Follow-up of AEs will end either when the 
symptom or illness resolves completely, up to 30 days past the end of study 
participation (if ongoing at the time of study exit) or until the investigator 
determines that the event has stabilized and will not completely resolve. 
Participants will be assessed at the 12 month visit for any potential adverse 
events that could be attributable to hydroxychloroquine. 
AEs to be reported include: 
 
All SAEs regardless of attribution  
 
All Cardiac AEs for Grade 2 and above that are attributed to 
intervention (possible, probable, and definite) 
 
All AEs grade 3 and above regardless of attribution 
Enrollment will be held and the SRC committee will meet if the following 
occur: 
 
Any SAEs with an attribution of  possible, probable, and definite 
 
Any Cardiac AEs for Grade 2 and above that are attributed to 
intervention (possible, probable, and definite) 
 
Any AEs grade 3 and above attributed to intervention (possible, 
probable, and definite) 
The SRC will review safety data and determine if the study can continue.  
8.3.2 AE/SAE Assessments 
All AE and SAE reporting will be conducted in compliance Sanford Health 
Policy HRP 024 New Information.  
AE assessments will be focused on body systems with potential known 
toxicities and well as other toxicities verbalized by the participant. 
All AE and SAEs will be assigned causality by the Investigator in their 
relationship to the study medication based on the following categories: 
 Definitely: clear evidence exists that the event was caused by the 
intervention 
 Probably: reasonable probability exists that the event was caused by 
the intervention 
 Possibly: reasonable possibility exists that the event may have been 
caused by the intervention 
 Unlikely: evidence exists that the event was caused by other factors; 
although the relationship of the event to the intervention cannot be 
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 Unrelated: the cause of the event is known and the event is in no way 
related to any aspect of the intervention  
SAEs must be reported to the lead site and study chair at 
SH_HCQ_Team@sanfordhealth.org as soon as possible, but no later than 24 
hours from the day the study team became aware of the event. Follow-up 
reports may be required or requested by the lead site or regulatory agency and 
should be completed promptly.  
IRB notification of SAEs is required per Sanford IRB reporting guidelines. 
Investigators and study personnel are responsible for knowing IRB reporting 
requirements. Reporting of SAEs, whether related or unrelated to the study 
participation, should follow the most stringent rules for reporting.  
The date of onset of the event, the date the site staff became aware of the event 
and determined it met the criteria of an SAE, and the date the event resolved 
or no longer fit the criteria of SAE will be documented in the source document 
and in the EDC system.  
8.3.3 Safety Review Committee (SRC) 
An independent SRC will be established with experienced members, none of 
whom are participating as study investigators, to monitor and evaluate the 
safety of subjects, to maintain oversight of study data and to monitor progress 
of the study. The committee will initially meet monthly and more frequently if 
concerns of safety are noted. The findings of the SRC will be submitted to the 
IRB within 10 days after the meeting.    All SAEs will be reported to the SRC 
as soon as possible after learning of the event. 
The Study Chair will review cumulative AEs and SAEs weekly and will share 
concerns with the SRC.  The SRC will make recommendations to the Study 
Chair regarding steps to ensure subject safety and the continued ethical 
integrity of the trial.  The SRC will review interim study results and consider 
the overall risk and benefit to trial participants.  The SRC will recommend to 
the Study Chair whether the trial should continue in accordance with the 
protocol.   
9.0 
Statistical Considerations  
 
9.1 
Statistical Hypothesis 
There will be a 50% decrease (relative risk reduction) in the conversion to infected 
status within the treatment arm compared to the control arm. 
9.2 
Sample Size Determination 
Cohort A: 
It is expected that 10% of exposed healthcare workers will convert to infected status 
without intervention.  The treatment arm will be assumed to have a conversion of 5% 
(50% relative reduction, 5% absolute risk reduction).  Due to the uncertainty of this 


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trial, a conservative 10% drop out rate is included in the calculation. Under these 
assumptions (Treatment: 5% infected, Control: 10% infected, α: 0.0492, Power: 
90%), the total sample size is 1356 patients (610 patients are needed in each arm + 
10% dropout = 1356 total patients).  
Cohort B: 
It is expected that 30% of exposed high risk patients will convert to infected status 
without intervention.  The treatment arm will be assumed to have a conversion of 
15% (50% relative reduction, 15% absolute risk reduction).  Due to the uncertainty of 
this trial, a conservative 10% drop out rate is included in the calculation. Under these 
assumptions (Treatment: 15% infected, Control: 30% infected, α: 0.0492, Power: 
90%), the total sample size is 383 patients (172 patients are needed in each arm + 
10% dropout = 383 total patients). 
9.3 
Statistical Analyses 
All baseline and demographic variables such as race, gender, age, height, and weight 
will be summarized.  Continuous variables will be summarized using mean, standard 
deviation, median, IQR, minimum and maximum.  Categorical variables will be 
presented using frequencies and percentages. 
Difference in infected status proportions between the treatment and control groups 
will be evaluated using Fisher’s exact test.  The number of adverse events, rate of 
occurrence, and severity by treatment group will be reported and statistically 
compared using non-parametric methods.  
Details of the analysis methods will be provided in the Statistical Analysis Plan 
(SAP), which will be finalized as early as possible after enrollment commences in 
order to minimize bias in the analysis strategy. 
 
9.4 
Interim Analysis 
An interim analysis will be conducted to determine if the study should be stopped due 
to safety concerns or efficacy. Using O’Brien-Fleming approach, the interim analysis 
will use a significance level of α= 0.0054 and the final analysis will use a significance 
level of 0.0492.  The interim safety analysis will be performed when 50% of subjects, 
within their respective cohort, complete their 35 day follow-up.  Overall safety will be 
analyzed first, and if safety outcomes are statistically higher in the treatment group 
(α= 0.0054), enrollment will be stopped, participants will be unblinded and each 
cohort will be analyzed independently.  If safety has not been compromised the study 
maybe resumed after review and recommendation by the SRC.  Efficacy will be 
analyzed for early declaration of success. If power of 90% has been detected and a 
statistically significant change has been identified (α= 0.0054), that specific cohort 
will stop enrollment and the final analysis will be done with completed data from 
participants enrolled at that time, otherwise the study will continue enrolling patients 
and final analysis will be completed. 


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10.0 Regulatory, Ethical, and Study Oversight 
10.1 
Statement of Compliance 
This study will be conducted in accordance with this protocol, FDA and applicable 
local regulatory requirements.  
Before enrollment of participants into this study, the IRB will review and approve the 
protocol, informed consent documents, any promotional material/advertisements, and 
any other written information to be provided to the participants.  The Package Insert 
for hydroxychloroquine describing the investigational product will be provided to the 
IRB for review, see Appendix C. Drug information for vitamin D with calcium is 
provided in Section 6.3.  Also see Appendix D. The IRB’s composition or a statement 
that the IRB’s composition meets applicable regulatory criteria will be documented.  
If the protocol or any other information given to the participant is amended, the 
revised documents will be reviewed and approved by the IRB, where applicable. The 
protocol amendment will only be implemented upon the lead site’s receipt of approval 
and, if required, upon the lead site’s notification of applicable regulatory 
authority(ies) approval except for changes necessary to eliminate an immediate hazard 
to study participants. 
10.2 
Informed Consent  
Written informed consent will embody the elements of informed consent as required 
by 21 CFR 50.27 and the IRB and will be in accordance with all applicable laws and 
regulations. Site investigators will enroll participants according to the study eligibility 
criteria and in compliance with 21 CFR 50, Protection of Human Participants. The 
investigator will exercise no selectivity so that no bias is introduced from this source. 
The site investigator or qualified study team member must obtain documented consent 
from each potential participant prior to participating in a clinical study or future 
biomedical research. If there are changes to the participant’s status during the study 
(e.g., health or age of majority requirements), the investigator or study team member 
delegated this task must ensure the appropriate consent is in place. 
A copy of the consent form should be given to the participant before participation in 
the study. 
The initial ICF, any subsequent revised written ICF and any written information 
provided to the participant must receive Sanford IRB’s approval in advance of use. 
The participant should be informed in a timely manner if new information becomes 
available that may be relevant to the participant’s willingness to continue participation 
in the study. The communication of this information will be documented in the 
participant’s study chart.  Communication may take place in person, over the 
telephone or by mail.   
Specifics about a study and the study population will be added to the consent form 
template at the protocol level. 


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10.3 
Study Participant Confidentiality 
The investigator will comply with applicable participant privacy regulations/guidance 
as described as per the Health Insurance Portability and Accountability Act (HIPAA) 
and any additional local regulations. 
The lead site is committed to safeguarding participant confidentiality, to the greatest 
extent possible.  Unless required by law, only the investigator, lead site (or 
representative), IRB, and/or regulatory authorities will have access to confidential 
medical records that might identify the participant by name. 
The participant must be informed that his/her personal study-related data will be used 
by the lead site in accordance with local data protection law.  The level of disclosure 
must also be explained to the participant. 
The participant must be informed that his/her medical records may be examined by 
Clinical Research Staff for quality data review at each site or other authorized 
personnel appointed by the lead site, by appropriate IRB members, and by inspectors 
from regulatory authorities. 
10.4 
Risks and Benefits 
Potential participants will be informed of the risks and benefits of, as well as 
alternatives to, trial participation. At a minimum, trial designs will take into account 
the local standard of care. 
All participation in clinical trials is voluntary. Participants enter the trial only after 
informed consent is obtained. Participants may withdraw from a trial at any time, 
without any influence on their access to, or receipt of, medical care that may 
otherwise be available to them. 
10.5 
Ethics 
The study protocol, along with the required informed consent forms, will be approved 
by the Sanford IRB prior to the initiation of any research procedures (at the site).  In 
addition to details described in the sections above (informed consent, confidentiality, 
and risks and benefits), the investigators should review and consider ethical 
ramifications in the design and development of this protocol, in accordance with 21 
CFR 50. Protections of Human Participants.  The investigators will make every effort 
to minimize and monitor risks and discomforts to participants throughout the course 
of the study. 
10.6 
Study Documentation and Case Report Forms (CRFs) 
The data collection tool for this study will be defined CRF/eCRFs to be completed by 
study-site personnel. The investigator will maintain complete and accurate study 
documentation in a separate file.  Study documentation may include medical 
records/electronic medical records, records detailing the progress of the study for each 
participant, signed informed consent forms, drug disposition records, correspondence 
with the IRB and the study monitor/lead site, screening and consent information, 
CRFs/eCRFs, AE/SAE reports, laboratory reports, participant diaries/questionnaires, 
data clarifications requested by the lead site study team, and any other documentation 


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deemed relevant and pertinent to the study and the study participants.  Participant data 
necessary for analysis and reporting will be entered into a validated database or data 
system in accordance with Title 21 of the Code of Federal Regulations (21 CFR) Part 
11.  The site investigator is responsible for the procurement of data and for the quality 
of data recorded on the CRFs/eCRFs.  
10.7 
Document and Data Retention 
Health information will be used to conduct this study to determine research results. 
Health information is used to report results of research to federal regulatory agencies, 
if applicable. Health information from study participants may be included in an audit 
to ensure that the study follows regulations, policies, and study plans.  
All records will be maintained indefinitely. Sanford policy on record retention and 
destruction specific to research studies will be followed for Sanford sites.  Non-
Sanford sites will follow their policy for record retention and destruction   Clinical 
data will be stored indefinitely.   If a subject chooses to withdrawal consent to the 
study, he/she may request to withdraw.  No further data will be collected on the 
subject, but any data collected prior to withdrawal will be and used for analysis.  
The site will retain study documentation and data (electronic case report forms) in 
accordance with applicable regulatory requirements and each site document and data 
retention policy. 
10.8 
Direct Access to Source Data/Documents 
The investigator/study site will cooperate and provide direct access to study 
documents and data, including source documentation for quality data review by the 
study team at each site, audits by the lead site or lead site’s representatives, review by 
the IRB, and inspections by applicable regulatory authorities. If contacted by an 
applicable regulatory authority, the investigator will notify the lead site of contact, 
cooperate with the authority, provide the lead site with copies of all documents 
received from the authority, and allow the lead site to comment on any responses. 
10.9 
Protocol Compliance 
Deviations from the approved study protocol will be noted by study staff and will be 
reported to the IRB by the investigator/treating physician per Sanford IRB policy 
HRP 024 New Information for reporting protocol deviations/violations. 
10.10 Publication Policy 
Manuscript submission for publication of the results of this study, or any aspect of 
work directly related to the study, will be decided by the investigators.  Any 
investigator can submit a publication concept proposal including proposed authorship 
order to the rest of the investigators for review, which will take place within 30 days 
after a proposal has been submitted. 
 
 
 


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Appendix A: Abbreviations 
 
AE / SAE  
Adverse Event / Serious Adverse Event 
BCVA 
 
Best Corrected Distance Visual Acuity 
CTCAE  
Common Terminology Criteria for Adverse Events 
CDC 
 
Center for Disease Control 
CFR  
 
Code of Federal Regulations 
CHF 
 
Congestive Heart Failure 
CNS 
 
Central Nervous System 
COVID 
 
Coronavirus Disease 
CRF / eCRF 
Case Report Form / Electronic Case Report Form 
ECG 
 
Electrocardiogram 
EDC 
 
Electronic Data Capture 
FDA  
 
Food and Drug Administration 
GCP 
 
Guidelines for Good Clinical Practices  
HIPAA   
Health Insurance Portability and Accountability Act 
ICF  
 
Informed Consent Form 
IRB  
 
Institutional Review Board 
NCI 
 
National Cancer Institute  
PI  
 
Principal Investigator 
PO  
 
By Mouth 
PPE 
 
Personal Protection Equipment 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2  
SD-OCT  
Spectral Domain Ocular Coherence Tomography 
SoA  
 
Schedule of Activities 
SOC 
 
Standard of Care 
SRC 
 
Safety Review Committee 
VF  
 
Visual Field  
 
 


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Appendix B:  Protocol Amendment History 
 
 
DOCUMENT HISTORY 
Document 
Date 
[Amendment X] 
[Day-Mon-Year] 
[Amendment X] 
[Day-Mon-Year] 
[Amendment X] 
[Day-Mon-Year] 
Original Protocol 
[Day-Mon-Year] 
 
 
Amendment X 
Overall Rationale for the Amendment: (Primary reason for this amendment at the top) 
Section # and 
Name 
Description of Change 
Brief Rationale 
[INSERT] 
[INSERT] 
[INSERT] 
[INSERT] 
[INSERT] 
[INSERT] 
[INSERT] 
[INSERT] 
[INSERT] 
 
 
 
 
 
 
 
 
 


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Appendix C:  Hydroxychloroquine Drug Information 
  


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Appendix D:  Exclusion Medication List  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Digoxin 
Praziquantel 
Mefloquine 
Antacids 
Tamoxifen citrate 
Kaolin 
Methotrexate 
Cimetidine 
Cyclosporine 
Ampicillin 
Insulin 
Laxatives 
Antidiabetic drugs 
Enemas 
Loop diuretics 
Amphotericin B 
Thiazides 
High dose 
corticosteroids 
Pyridostigmine 
Proton pump inhibitors 
 
Neostigmine 
 
Pyridostigmine 


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The last revision date: March 19, 2020 
 
See Note below for safe use of this Table 
The drug list below contains drugs from the categories: 
Known Risk of TdP, 
Possible 
Risk of TdP AND filtered by 
Market filter: Only Drugs on US Market AND filtered by Keyword --> " " 
Generic 
Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Alfuzosin 
Uroxatral 
Alpha-1 adrenergic 
blocker 
Benign 
prostatic 
hyperplasia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Amiodarone 
Cordarone, 
Pacerone, 
Nexterone 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injectio
n 
Anagrelide 
Agrylin, Xagrid 
Phosphodiesterase 3 
inhibitor 
Thrombocythe
mia 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral 
Apalutamide 
Erleada 
Nonsteroidal 
antiandrogen 
Cancer 
(prostate) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Apomorphine 
Apokyn, Ixense, 
Spontane, Uprima 
Dopamine agonist 
Parkinson's 
disease 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
sublingua
l, 
injection 
Aripiprazole 
Abilify, Aripiprex 
Antipsychotic, 
atypical 
Schizophrenia, 
depression 
(adjunct) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injectio
n 
Arsenic trioxide 
Trisenox 
Anti-cancer 
Cancer 
(leukemia) 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
injection 
CredibleMeds Filtered QTDrug List 


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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Artemether/Lumefantrin e 
Coartem 
Anti-malarial 
Marlaria 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Asenapine 
Saphris, Sycrest 
Antipsychotic, 
atypical 
Schizophrenia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
sublingual 
Atomoxetine 
Strattera 
CNS stimulant 
ADHD 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Azithromycin 
Zithromax, Zmax 
Antibiotic 
Bacterial infection Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection 
Bedaquiline 
Sirturo 
Antibiotic 
Tuberculosis, 
Multi-drug 
resistant 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Bendamustine 
Treanda, Treakisym, 
Ribomustin, Levact 
Anti-cancer 
Cancer 
(Leukemia, 
lymphoma) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Bepridil 
Vascor 
Antianginal 
Angina Pectoris 
(heart pain) 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral 
Betrixaban 
Bevyxxa 
Anticoagulant 
Anticoagulant 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Bortezomib 
Velcade, Bortecad 
Proteasome inhibitor Cancer (multiple 
myeloma, 
lymphoma) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Bosutinib 
Bosulif 
Anti-cancer 
Cancer (leukemia) Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Buprenorphine 
Butrans, Belbuca, Bunavail, 
Buprenex, Subutex, 
Suboxone, Zubsolv 
Opioid agonist 
Narcotic 
addiction and 
pain 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
sublingual, 
topical, 
injection 
Cabozantinib 
Cometriq 
Anti-cancer 
Cancer (renal 
cell) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Capecitabine 
Xeloda 
Anti-cancer 
Cancer (GI, 
Breast) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Ceritinib 
Zykadia 
Anti-cancer 
Cancer (Lung) Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Cesium Chloride 
Energy Catalyst 
Toxin 
Alternative 
therapy 
cancer 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection 
Chloroquine 
Aralen 
Antimalarial 
Malaria 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Chlorpromazine 
Thorazine, Largactil, 
Megaphen 
Antipsychotic / 
Antiemetic 
Nausea, 
Schizophrenia, 
many others 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection, 
suppository 
Cilostazol 
Pletal 
Phosphodiesterase 3 
inhibitor 
Intermittentcl 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Ciprofloxacin 
Cipro, Cipro-XR, Neofloxin 
Antibiotic 
Bacterial 
infection 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection 
Citalopram 
Celexa, Cipramil 
Antidepressant, 
SSRI 
Depression 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Clarithromycin 
Biaxin, Prevpac 
Antibiotic 
Bacterial infection Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
inhaled 
Clozapine 
Clozaril, Fazaclo, Versacloz 
Antipsychotic, 
atypical 
Schizophrenia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Cobimetinib 
Cotellic 
Anti-cancer 
Cancer 
(Melanoma) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Crizotinib 
Xalkori 
Anti-cancer 
Cancer (Non-
small cell lung 
cancer, 
metastatic) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Dabrafenib 
Tafinlar 
Anti-cancer 
Cancer 
(melanoma) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Dasatinib 
Sprycel 
Anti-cancer 
Cancer (leukemia) Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Degarelix 
Firmagon, Ferring 
Anti-androgen 
Cancer (prostate) Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection, 
suppository 
Desipramine 
Pertofrane, Norpramine 
Antidepressant, 
Tricyclic 
Depression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Deutetrabenazine 
Austedo 
Vesicular monamine 
transporter 2 inhibitor 
Chorea 
(Huntington's 
disease) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic Use 
Risk Category 
Route 
Dextromethorphan/Quini 
dine 
Nuedexta 
Unknown 
Pseudobulbar affect 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Disopyramide 
Norpace 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection 
Dofetilide 
Tikosyn 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Dolasetron 
Anzemet 
Antiemetic 
Nausea, vomiting 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection 
Donepezil 
Aricept 
Cholinesterase 
inhibitor 
Dementia (Alzheimer's 
Disease) 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Dronedarone 
Multaq 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Efavirenz 
Sustiva 
Antiviral 
HIV/AIDS 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Eliglustat 
Cerdelga 
Glucosylceramide 
synthase inhibitor 
Gaucher's disease 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Encorafenib 
Braftovi 
BRAF inhibitor 
Cancer 
(Melanoma) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Entrectinib 
Rozlytrek 
Anti-cancer 
Cancer (Lung) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Epirubicin 
Ellence, Pharmorubicin, 
Epirubicin Ebewe 
Anti-cancer 
Cancer 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Eribulin mesylate 
Halaven 
Anti-cancer 
Cancer (breast, 
metastatic) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Erythromycin 
E.E.S., Robimycin, EMycin, 
Erymax, Ery-Tab, Eryc 
Ranbaxy, Erypar, Eryped, 
Erythrocin Stearate Filmtab, 
Erythrocot, E-Base, 
Erythroped, Ilosone, MY-E, 
Pediamycin, Abboticin, 
Abboticin-ES, Erycin, PCE 
Dispertab, Stiemycine, 
Acnasol, Tiloryth 
Antibiotic 
Bacterial 
infection, 
increase GI 
motility 
Risk of TdPAnd 
Avoid in 
congenital long 
QT 
oral, 
injection 
Escitalopram 
Cipralex, Lexapro, Nexito, 
Anxiset-E, Exodus, Esto, 
Seroplex, Elicea, Lexamil, 
Lexam, Entact, Losita, 
Reposil, Animaxen, Esitalo, 
Lexamil 
Antidepressant, 
SSRI 
Depression 
(major), 
anxiety 
disorders 
Risk of TdPAnd 
Avoid in 
congenital long 
QT 
oral 
Ezogabine (Retigabine) 
Potiga, Trobalt 
Anticonvulsant 
Seizures, Partial Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Felbamate 
Felbatol 
Anticonvulsant 
Seizures 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Fingolimod 
Gilenya 
Sphingosine 
phospate receptor 
modulator 
Multiple Sclerosis Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Flecainide 
Tambocor, Almarytm, 
Apocard, Ecrinal, Flécaine 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral 
Fluconazole 
Diflucan, Trican 
Antifungal 
Fungal infection 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection 
Fluorouracil (5-FU) 
Adrucil, Carac, Efudex, 
Efudix 
Anti-cancer 
Cancer 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Gemifloxacin 
Factive 
Antibiotic 
Bacterial infection Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Gilteritinib 
Xospata 
Antineoplastic 
Cancer (Acute 
Myeloid 
Leukemia) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Glasdegib 
Daurismo 
Anti-cancer 
Cancer (Acute 
myeloid leukemia) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Granisetron 
Kytril, Sancuso, Granisol 
Antiemetic 
Nausea, vomiting Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection, 
topical 
Haloperidol 
Haldol, Aloperidin, 
Bioperidolo, Brotopon, Dozic, 
Duraperidol, Einalon S, 
Eukystol,  Halosten, 
Keselan, Linton, Peluces, 
Serenace, Serenase, 
Sigaperidol 
Antipsychotic 
Schizophrenia, 
agitation 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic Use Risk Category 
Route 
Hydrocodone - ER 
Hysingla™ ER, Zohydro ER 
Analgesic 
Pain, severe 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
suppository 
Hydroxychloroquine 
Plaquenil, Quineprox 
Antimalarial, 
Anti-inflammatory 
Malaria, SLE, 
rheumatoid 
arthritis 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Iloperidone 
Fanapt, Fanapta, Zomaril 
Antipsychotic, 
atypical 
Schizophrenia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Imipramine 
(Melipramine) 
Tofranil 
Antidepressant, 
Tricyclic 
Depression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Inotuzumab ozogamicin 
Besponsa 
Anti-cancer 
Cancer (acute 
lymphocytic 
leukemia} 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Isradipine 
Dynacirc 
Antihypertensive 
Hypertension 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Ivosidenib 
Tibsovo 
IDH1 inhibitor 
Cancer (Acute 
myeloid leukemia) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Lapatinib 
Tykerb, Tyverb 
Anti-cancer 
Cancer (breast, 
metastatic) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Lefamulin 
Xenleta 
Antibiotic 
Community 
acquired 
pneumonia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Lenvatinib 
Lenvima 
Anti-cancer 
Cancer (Thyroid) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Leuprolide (Leuprorelin) Lupron, Eligard, Viadur, 
Carcinil, Enanton, Leuplin, 
Lucrin, Procren, Prostap 
Anti-androgen 
Cancer (prostate) Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Levofloxacin 
Levaquin, Tavanic 
Antibiotic 
Bacterial infection Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection 
Lithium 
Eskalith, Lithobid 
Antimanic 
Bipolar disorder 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Lofexidine 
Lucemyra 
Alpha-2-adrenergic 
agonist, central 
Opioid 
withdrawal 
syndrome 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Lopinavir/Ritonavir 
Kaletra, Aluvia 
Antiviral 
HIV/AIDS 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Lumateperone 
Caplyta 
Antipsychotic, 
atypical 
Schizophrenia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Lurasidone 
Latuda 
Antipsychotic, 
atypical 
Schizophrenia, 
biopolar disorder 
and others 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Maprotiline 
Ludiomil 
Anti-depressant, 
Tetracyclic 
Depression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Memantine 
Namenda XR 
NMDA receptor 
antagonist 
Alzheimer's 
disease 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Methadone 
Dolophine, Symoron, 
Amidone, Methadose, 
Physeptone, Heptadon 
Opioid agonist 
Narcotic 
dependence, 
pain 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection 
Midostaurin 
Rydapt 
Anti-cancer 
Cancer 
(Acute 
myeloid 
leukemia) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Mifepristone 
Korlym, Mifeprex 
Progesterone 
antagonist 
Pregnancy 
termination 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Mirabegron 
Myrbetriq 
Beta3 adrenergic 
antagonist 
Bladder spasm 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Mirtazapine 
Remeron 
Antidepressant, 
Tetracyclic 
Depression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Moexipril/Hydrochlorothi 
azide 
Uniretic, Univasc 
Antihypertensive 
Hypertension, 
diuresis 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Moxifloxacin 
Avelox, Avalox, Avelon 
Antibiotic 
Bacterial infection Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection 
Necitumumab 
Portrazza 
Anti-cancer 
Cancer (Lung) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Nicardipine 
Cardene 
Antihypertensive 
Hypertension 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Nilotinib 
Tasigna 
Anti-cancer 
Cancer (leukemia) Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Nortriptyline 
Pamelor, Sensoval, Aventyl, 
Norpress, Allegron, Noritren, 
Nortrilen 
Antidepressant, 
Tricyclic 
Depression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Nusinersen 
Spinraza 
Antisense 
oligonucleotide 
Spinal Muscular 
Atrophy 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Ofloxacin 
Floxin 
Antibiotic 
Bacterial infection Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Ondansetron 
Zofran, Anset, Ondemet, 
Zuplenz, Emetron, Ondavell, 
Emeset, Ondisolv, Setronax 
Antiemetic 
Nausea, vomiting Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral, 
injection, 
suppository 
Osimertinib 
Tagrisso 
Anti-cancer 
Cancer (EGFR 
pos. NSC Lung 
cancer) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Oxaliplatin 
Eloxatin 
Anti-cancer 
Cancer 
Risk of 
TdPAnd Avoid 
in congenital 
long QT 
injection 
Paliperidone 
Invega, Xepilon 
Antipsychotic, 
atypical 
Schizophrenia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Palonosetron 
Aloxi 
Antiemetic 
Nausea, vomiting Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Panobinostat 
Farydak 
Histone deacetylase 
inhibitor 
Cancer, Multiple 
myeloma 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic Use 
Risk Category 
Route 
Pasireotide 
Signifor 
Somatostatin analog Cushings Disease 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
injection, 
topical 
Pazopanib 
Votrient 
Anti-cancer 
Cancer (renal cell, 
sarcoma) 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Pentamidine 
Pentam 
Antifungal 
Fungal infection 
(Pneumocystis 
pneumonia) 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
injection, 
inhaled 
Perphenazine 
Trilafon, Etrafon/Triavil, 
Decentan 
Antipsychotic 
Schizophrenia 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection 
Pimavanserin 
Nuplazid 
Antipsychotic, 
atypical 
Psychosis, 
Parkinson's Disease 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Pimozide 
Orap 
Antipsychotic 
Tourette's Disorder 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Pitolisant (Tiprolisant) 
Wakix 
Histamine 3 
antagonist/inverse 
agonist 
Narcolepsy 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Pretomanid 
Antitubercular 
Tuberculosis, 
extensively drug 
resistant 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 


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under applicable law 
 
 
 
Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic Use 
Risk Category 
Route 
Primaquine phosphate 
Antimalarial 
Malaria 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Procainamide 
Pronestyl, Procan 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
injection 
Promethazine 
Phenergan 
Antipsychotic / 
Antiemetic 
Nausea, vomiting 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection, 
suppository 
Quinidine 
Quinaglute, Duraquin, 
Quinact, Quinidex, Cin-Quin, 
Quinora 
Antiarrhythmic 
Arrhythmia 
Risk of 
TdPAnd 
Avoid in 
congenital 
long QT 
oral, 
injection 
Ribociclib 
Kisqali 
Anti-cancer 
Cancer (breast) 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Rilpivirine 
Edurant, Complera, Eviplera, 
Juluca 
Antiviral 
Viral infection 
(HIV/AIDS) 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Romidepsin 
Istodax 
Histone deacetylase 
inhibitor 
Cancer (lymphoma) 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
injection 
Saquinavir 
Invirase(combo) 
Antiviral 
Viral infection 
(HIV/AIDS) 
Possible Risk 
of TdPAnd 
Avoid in 
congenital 
long QT 
oral 


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Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Siponimod 
Mayzent 
Multiple Sclerosis Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Sorafenib 
Nexavar 
Anti-cancer 
Cancer (liver, 
renal cell, 
metastatic 
thyroid) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Sotalol 
Betapace, Sotalex, Sotacor 
Antiarrhythmic 
Arrhythmia 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Sunitinib 
Sutent 
Anti-cancer 
Cancer (GIST, 
renal cell, 
pNET) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Tacrolimus 
Prograf, Prograf, Advagraf, 
Protopic 
Immunosuppressant Immune 
suppression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Tamoxifen 
Nolvadex, Istubal 
Anti-cancer 
Cancer (breast) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Tazemetostat 
Tazverik 
Anti-cancer 
Epithelioid 
sarcoma 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Telavancin 
Vibativ 
Antibiotic 
Bacterial infection Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
injection 
Tetrabenazine 
Nitoman, Xenazine 
Vesicular 
Monoamine 
Transporter 2 
Inhibitor 
Chorea 
(Huntington's 
disease) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 


CONFIDENTIAL 
 
 
 
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under applicable law 
 
 
 
Generic Name 
Brand Names (Partial List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Thioridazine 
Mellaril, Novoridazine, Thioril Antipsychotic 
Schizophrenia 
Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Tipiracil/Trifluridine 
Lonsurf 
Anti-cancer 
Cancer 
(Metastatic 
colorectal) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Tizanidine 
Zanaflex, Sirdalud 
Muscle relaxant 
Muscle 
spasticity 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Tolterodine 
Detrol, Detrusitol 
Muscle relaxant 
Bladder spasm 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Toremifene 
Fareston 
Estrogen 
agonist/antagonist 
Cancer (breast, 
metastatic) 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Tramadol 
Crispin, Ralivia ER, Ralivia 
Flashtab, Tramadolum, 
Tramal, Tramodol, Tridural, 
Ultram, Ultram ER, Zydol, 
Ixprim, Zaldiar, Topalgic 
Analgesic 
Pain 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection, 
suppository 
Trimipramine 
Surmontil, Rhotrimine, 
Stangyl 
Antidepressant, 
Tricyclic 
Depression 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 
Valbenazine 
Ingrezza 
Vesicular monamine 
transporter 2 inhibitor 
Tardive 
Dyskinesia 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral 
Vandetanib 
Caprelsa 
Anti-cancer 
Cancer (thyroid) Risk of TdPAnd 
Avoid in 
congenital 
long QT 
oral 
Vardenafil 
Levitra 
Phosphodiesterase 5 
inhibitor 
Erectile 
dysfunction 
Possible Risk of 
TdPAnd Avoid in 
congenital 
long QT 
oral, 
injection 


CONFIDENTIAL 
 
 
 
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unauthorized disclosure under applicable law 
 
 
Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic 
Use 
Risk Category 
Route 
Vemurafenib 
Zelboraf 
Anti-cancer 
Cancer 
(melanoma) 
Possible Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral 
Venlafaxine 
Effexor, Efexor 
Antidepressant, 
SNRI 
Depression 
Possible Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral 
Vorinostat 
Zolinza 
Histone deacetylase 
inhibitor 
Cancer 
(lymphoma) 
Possible Risk of 
TdPAnd Avoid 
in congenital 
long QT 
oral 
 
Note: Medicines on this list are reviewed on an ongoing basis to assure that the available evidence 
supports their continued placement on this list. The list changes regularly and we recommend 
checking the website at crediblemeds.org for the most up-to-date information. There may be many 
additional brand names that are not listed on this form. 
Disclaimer and Waiver: The information presented is intended solely for the purpose of providing general 
information about 
health-related matters. It is not intended for any other purpose, including but not limited to medical advice 
and/or treatment, nor is it intended to substitute for the users’ relationships with their own health care 
providers. To that extent, by use of this website and the information it contains, the user affirms the 
understanding of the purpose and releases AZCERT, Inc. from any claims arising out of his/her use of the 
website and its lists. The absence of drugs from these lists should not be considered an indication that they 
are free of risk of QT prolongation or torsades de pointes. Many medicines have not been tested for this risk in 
patients, especially those with congenital long QT syndrome. 
  
 
 


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unauthorized disclosure under applicable law 
 
 
Appendix E: References 
 
Haeusler IL, Chan XHS, Guerin PJ, White NJ. The arrhythmogenic cardiotoxicity of the 
quinoline and structurally related antimalarial drugs: A systematic review. BMC Med. 
2018;16:200. PMC6220451. 
Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. 
Revised recommendations on screening for chloroquine and hydroxychloroquine 
retinopathy. Ophthalmology. 2011;118(2):415–422. doi:10.1016/j.ophtha.2010.11.017 
Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing 
Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome 
Coronavirus 2 (SARS-CoV-2) [published online ahead of print, 2020 Mar 9]. Clin Infect Dis. 
2020;ciaa237. doi:10.1093/cid/ciaa237 
Vitamin D reference:  https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ 
 
 

ICF_003.pdf: 
Hydroxychloroquine as Post-Exposure 
Prophylaxis Against COVID-19 Infection 
(PEPCOH) 
NCT04372017 
Informed Consent Document 
Continuing Review Date 03.11.2021 


Version: 1.0 (2020.05.15)
Page 1 of 7
Sanford Health Consent and HIPAA Authorization to Participate in a Research Study
Study Title: 
Post-Exposure Prophylaxis for COVID-19 with Hydroxychloroquine (PEPCOH)
Sponsor: 
Sanford Health 
Principal Investigator: 
Susan Hoover, MD, PhD
Site Name: 
Sanford Health
Sioux Falls, SD
You are being asked to take part in a research study sponsored by Sanford Health.  Dr. Susan Hoover is the 
Principal Investigator of this research study. A Principal Investigator has the overall responsibility for the 
conduct of the research. However, there are other individuals who are part of the research team.
OVERVIEW AND KEY INFORMATION 
Research is the process of solving problems and finding facts in an organized way. The information below will 
give you key information to help you decide why you may or may not want to be in the research study.
Please read this document carefully and do not hesitate to ask questions about this information and ask the 
study staff to explain the words or information that you do not understand. You should not join this research 
study until all of your questions are answered.
Voluntary. Participation is voluntary, meaning that you may choose not to take part or you may choose to
leave the research study (withdraw) at any time without loss of benefits. Your decision whether or not to
participate will not affect your current of future relations with Sanford Health.
Purpose. The purpose of this study is to see if hydroxychloroquine will reduce the chances of developing
a COVID-19 infection after a high-risk exposure.  Hydroxychloroquine is not FDA approved to treat or
prevent COVID 19 and it is an experimental drug for this research.
Participation. The length of your participation will be 12 months: 5 days of treatment with 
hydroxychloroquine or placebo with follow-up phone calls at day 3, day 5, day 14, day 35 and 12 
months.
Risks. There are potential risks with this research study. The primary risk is related to the study drug. 
Common side effects include nausea, vomiting, diarrhea and loss of appetite.  More serious side effects 
such as cardiac effects, vision damage, muscle damage, nerve damage, suicidal behavior, low blood 
sugar and skin effects.  These risks will be explained in more detail later in this document.  The study 
team will review your medications and medical history to make sure you are not at an increased risk of 
side effects.  
Confidentiality. There is the risk of a breach of confidentiality, the unexpected release of your 
personal health information. While we cannot guarantee absolute confidentiality, we will use all 
available security measures to minimize the risk that this information is given to someone who is not 
involved in the study. 
In addition to the risks described, there may be unforeseen risks with this research that may hurt you in ways 
that are currently unknown.
Benefits. You may or may not benefit from this study.  It is currently unknown whether or not
hydroxychloroquine will prevent the development of COVID-19 following an exposure.   We cannot
promise any benefits to others from participation in this research. However, the information we gain from
this study could help future healthcare workers and high-risk people who have been exposed to COVID-
19.
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Alternatives. The alternative to this study is to not participate. Whether or not you choose to take part, 
your medical care will continue as planned by your physician.
What will happen during this study?
We are asking you to participate in this research study because you are 1) a healthcare worker and have had a 
positive exposure to COVID-19 in the workplace or in the community or; 2) you are considered a high-risk 
individual who has had a positive exposure to COVID-19.  Each of these groups are called cohorts. 
Before signing this document, study staff will review this consent form and study details with you and answer 
any questions you may have about the study.  If you choose to participate and sign the informed consent form, 
the study team will collect some basic information about your health and any medications you might be 
taking.  If the study team determines that you meet all of the criteria for participation in this study, you will be 
enrolled and randomly assigned to receive hydroxychloroquine or placebo.  The treatment you get will be 
chosen by chance, like flipping a coin.  You will have an equal chance of getting either treatment.  Neither you 
nor the study team will know if you are receiving hydroxycholoroquine or Vitamin D with calcium (placebo).
The two treatment groups are as follows:
Control Group: 
You will receive 5 days of Vitamin D with calcium, along with instructions for 
dosing and a pill diary.
Treatment Group: 
You will receive 5 days of hydroxychloroquine along with instructions for 
dosing and a pill diary.
Both the Control Group and the Treatment Group will complete a pill diary to confirm that you took the study 
medication correctly.  Both groups will also receive follow-up phone calls from the study team on days 3, 5, 
14, 35 and 12 months to see if you have any symptoms of or have tested positive for COVID-19, or if you’ve 
had any side effects from the medication.  
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    Trial Schema                   
Approved by Sanford IRB 05-19-2020.             


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ADDITIONAL INFORMATION
There are potential risks in this research study with both hydroxychloroquine and Vitamin D with calcium.  
The study team will review your medical history and medications to make sure that you are not at an increased 
risk.  
Hydroxychloroquine: There are known risks with hydroxychloroquine.  Common side effects 
may include nausea, vomiting, diarrhea and loss of appetite.  Rarely, other more severe side effects 
are seen.  

Retinopathy (vision damage)- irreversible retinal damage has been seen in some patients, 
however this is seen most often in patients who have taken hydroxychloroquine for at least 
5 years.  

Cardiac (heart) Effects Cardiomyopathy and QT Prolongation- Cardiomyopathy is a disease 
of the heart muscle that makes it harder for your heart to pump blood.  There have been 
cases of life-threatening and fatal cardiomyopathy with use of hydroxychloroquine.  QT 
prolongation is a heart rhythm condition that can potentially cause fast, chaotic heartbeats.  
Certain medical conditions and medications increase your risk of these cardiac side effects.  
Your health history will be thoroughly reviewed to make sure you are not at an increased 
risk.  If you notice your heart beating irregularly, it is important to contact your doctor or 
call 911 if it is an emergency.  

Myopathy (muscle damage) and Neuropathy (nerve damage)- muscle and nerve damage 
leading to weakness and wasting away of muscle groups has been reported.  

Suicidal behavior has been rarely reported in patients treated with hydroxychloroquine

Hypoglycemia (low blood sugar)- hydroxychloroquine has been shown to cause severe 
hypoglycemia including loss of consciousness that could be life threatening in patients 
treated with or without diabetes medications.  

Dermatologic (skin) Effects- skin reactions to hydroxychloroquine may occur.

If you are pregnant, this treatment may hurt your baby or your pregnancy in ways that are 
unknown. You will not be allowed to take this drug if you are pregnant.  You will be 
responsible for using effective birth control methods during the treatment phase of this trial. 
Vitamin D with calcium (Placebo): While Vitamin D with calcium is a common supplement, there 
are some risks with the medication.  The amount of calcium in 5 days of the Vitamin D is the 
equivalent of taking 1/2 of a standard calcium tablet and should pose no additional risk.

Renal (Kidney)- Decreased kidney function including excessive amount of urination, 
having to urinate at night, and increased calcium and nitrogen compounds in the urine.

Central Nervous System- mental retardation, disorientation and confusion

Soft Tissues- calcification (hardening) of tissues including the heart, blood vessels, kidney 
tubules and lungs

Skeletal- osteoporosis (brittle fragile bones) in adults, vague aches, stiffness and weakness

Gastrointestinal (stomach and intestines)- nausea, weight loss and constipation

Metabolic- mild acidosis (excessive acid in the body), anemia and weight loss

Pregnancy- heart defects, facial deformities and mental retardation have been recorded in 
pregnant women taking excessive amounts of Vitamin D
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Confidentiality and Privacy
While we cannot guarantee absolute confidentiality, we will use all available security measures to minimize 
the risk that this information would be given to someone outside of the study. Your study record may be 
reviewed by or disclosed to other researchers, the Sanford Institutional Review Board (IRB), Sanford 
Research Compliance, and the Food and Drug Administration (FDA).
Researchers would like to use your health information for research. This information includes data that 
identifies you. If you agree to this research, you give permission to the research team to use or disclose 
(release) your health information that identifies you.
An Electronic Medical Record (EMR) is an electronic version of the record of your care within a health 
system. An EMR is simply a computerized version of a paper medical record.  If you are receiving care or 
have received care at Sanford (outpatient or inpatient) and are participating in a Sanford research study, results 
of research‐related procedures (i.e. laboratory tests, imaging studies and clinical procedures) may be placed in 
your existing EMR maintained by Sanford.
By agreeing to this research, you authorize Sanford Health to use and/or disclose (release) your health 
information for this research. Those persons who receive your health information may not be required by 
Federal privacy laws (such as the Privacy Rule) to protect it and may share your information with others 
without your permission, if permitted by laws governing them. This authorization expires at the end of the 
research study. 
You do not have to agree to this authorization, but if you do not, you may not participate in this study. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. 
This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time.
You may be withdrawn at any time at the discretion of the principal investigator for safety, behavioral, 
compliance, or administrative reasons.  Data that has already been collected will be kept and used for analysis.   
If you wish to discontinue study medication or withdraw from the study prior to completing the 5 day course, 
please contact the study team.  Data that has been already been collected will be kept and used for analysis, 
but no further information will be collected. Also, even if you revoke your authorization, health information 
already obtained about you may be used or disclosed as necessary to maintain the integrity or reliability of the 
current research. To withdraw from this research study or revoke authorization to use or disclose your health 
information, you must contact the study team in writing at the below address:
Susan Hoover, MD, PhD
Attn: SH HCQ Trial
Sanford Research
2301 E. 60th Street North
Sioux Falls, SD 57104-0569
We may publish the results of this research. However, we will keep your name and other identifying 
information confidential.  You will be informed by the research investigator[s] of this study about any 
significant new findings that develop during the study which may influence your willingness to stay in the 
research.  If the research with your identifiable information gives results that have meaning for your health, 
the researchers will contact you to let you know what they have found.  The information collected for this 
study might be de-identified (identifiers removed, such as name, address, and date of birth) and used for future 
research search studies or distributed to another investigator for future research studies without your additional 
informed consent. 
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Who is funding this study?
This study is funded by the state of South Dakota and Sanford Health. 
Will it cost me anything to be in this study?
You will not have additional costs for being in this study. You and your insurance company will be charged 
for the health care services for which you would ordinarily be responsible to pay.
What if I am injured as a result of this study?
All research involves some risk of injury. In spite of all precautions, you might develop medical complications 
from participating in this study. If such complications arise, the investigator and the research study staff will 
assist you in obtaining appropriate medical treatment. In the event that you have an injury or illness that is 
directly caused by your participation in this study, reimbursement for all related costs of care will be sought 
first from your insurer, managed care plan, or other benefits program. You will be responsible for any 
associated co-payment or deductible as required by your insurance. If costs of care related to such an injury 
are not covered by your insurer, managed care plan, or other benefits program, you may be responsible for 
these costs. There are no plans to compensate you for a research related injury or illness. 
You do not waive any liability rights for personal injury by signing this form.
Will I be paid for participating in this study?
You will not be paid for being in this research study.
Email Communication 
We would like your permission to email you so we can contact you about involvement in future COVID-19 
related studies. Email is generally not a secure way to communicate, as there are ways for unauthorized users 
to access the communication. Email should not be used to convey information of an urgent nature. If you 
agree to provide and allow use of email, it would be limited to this study. We will never ask you to provide 
sensitive information like your Social Security number over email. You do not have to provide your email 
address to participate in this study.
___ Yes, the study team may use email to communicate with me for this study.
Email Address ___________________________________
___ No, I do not want the study team to communicate with me by email.
Physician Contact
We would like your permission to contact your primary care provider to let them know that you are 
participating in this trial.
____ Yes, the study team may contact my primary care provider
Name of Provider ________________________________
Facility ________________________________________
____ No, the study team may not contact my primary care provider
____ I do not have a primary care provider
If you have side effects related to the trial, contact your primary care physician.  In the event of a medical 
emergency dial 911 or go to your nearest emergency department.  
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Who can I talk to?
You may ask any questions you have now or later. If you have questions, concerns, or complaints, or think the 
research has hurt you, talk to the research team at 605-328-1368.
This research has been reviewed and approved by an Institutional Review Board (“IRB”). An Institutional 
Review Board is a group of people who protect the rights and welfare of people who participate in research. 
You may talk to them at (605) 312-6430 to discuss your rights while in this study, discuss problems, and to 
ask questions, offer input, or talk to someone besides the research team.
For this study you must be 18 years of age older to consent to participate in this research study.
Your signature documents your consent to take part in this research.
_____________________________________________________
________/________/________ 
Signature of Participant
     Day        Month        Year
_____________________________________________________
Printed Name of Participant
Approved by Sanford IRB 05-19-2020.