Clinical trial NCT04762771
Conditions: Covid19
Sponsor: Baptist Health South Florida
Start date: 2020-12-23; Completion date: 2021-09-20
Enrollment: 2 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is an open-label unblinded, randomized study to treat hospitalized covid-19 patients with colchicine plus current care (per institution treating physicians) vs. current care per institution treating physicians alone (the control arm)

Detailed description:
We aim to determine if Colchicine improves short-term outcomes in hospitalized coronavirus disease-19 (COVID-19) patients with cardiac manifestations of disease.

Myocardial injury has been described in up to 30% of COVID-19 infected patients, and portends a poor prognosis with currently no known treatment. Colchicine is a widely available, well-established, inexpensive, oral anti-inflammatory agent that has been FDA approved for the treatment of inflammatory disorders including gout and familial Mediterranean Fever. Trials have also shown its benefit to prevent post-cardiotomy syndrome, to treat acute and recurrent pericarditis, and reduce cardiovascular events after myocardial infarction. We extrapolate based on these indications and studies that colchicine may also help improve outcomes in hospitalized COVID-19 patients with evidence of cardiac injury.

This is an unblinded randomized study to treat hospitalized covid-19 patients with colchicine plus current care per institution treating physicians vs. current care per institution treating physicians alone (the control arm)

Arms: arm 1: Hospitalized covid-19 patients treated with colchicine plus current care per institution treating physicians. arm 2: Hospitalized covid-19 patients treated with current standard of care (per institution treating physicians) alone.
Interventions: intervention 1: Colchicine
Intervention descriptions: intervention 1: Colchicine dosing = 0.6 mg bid x 30 days Decrease dose to 0.3-0.6 mg daily or every other day in setting of gastrointestinal intolerance (nausea, diarrhea, emesis, abdominal discomfort) Decrease dose to 0.6 mg daily in the setting of weak or moderate CYP3A4 inhibitor Decrease dose to 0.3 mg daily in the setting of strong CYP3A4, P-glycoprotein inhibitors, or protease inhibitors Decrease dose to 0.3 mg daily in the setting of chronic kidney disease (CKD) stage ≥ 4 (CrCl ≤ 30 ml/min) or liver failure (aspartate aminotransferase /alanine aminotransferase \> 3x normal).

Decrease dose to 0.6 mg every 14 days in patients with end stage renal disease (ESRD) or requiring dialysis Route of Administration: oral

Protocol documents:
Prot_SAP_001.pdf: 
Miami Cardiac and Vascular Institute 
Clinical Research Protocol 
 
 
 
Official Title: 
Colchicine for the Treatment of Cardiac Injury in 
Hospitalized Patients with COVID-19 (COLHEART-19) 
NCT Number: 
NCT04762771 
Document Date: 
Protocol Version 2: 9/14/2020 
IRB Approval Date: 10/20/2020 
 
 
 
 
 
 
 


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Miami Cardiac and Vascular Institute  
Clinical Research Protocol 
Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients with COVID-19 
(COLHEART-19) 
Protocol Number: 
COLHEART-19 Version 2.0 
Version Date: 
September 14, 2020 
Investigational Product: 
Colchicine 
IND Number: 
Pending 
Development Phase: 
Phase 2 
Sponsor/Investigator: 
  
Sandra Chaparro, MD 
Funding Organizations: 
Miami Cardiac and Vascular Institute 
 
Principal Investigator: 
Name: Sandra Chaparro, MD 
 
Telephone: 786-596-3505 
Fax: 
786-533-9570 
E-mail: sandrach@baptisthealth.net 
Medical Monitors: 
Name: Sandra Chaparro, MD 
Telephone: 786-596-3505 
Fax: 
786-533-9570 
E-mail:  sandrach@baptisthealth.net 
 
 
 
 
 
 
 
 
 
 
 
 


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Approval: 
 
 
 
PI or Sponsor Signature (Name and Title)  
 
Date 
This confidential information about an investigational product is provided for the 
exclusive use of investigators of this product and is subject to recall at any time.  
The information in this document may not be disclosed unless federal or state law 
or regulations require such disclosure.  Subject to the foregoing, this information 
may be disclosed only to those persons involved in the study who have a need to 
know, with the obligation not to further disseminate this information.   
 
Principal Investigator   
Name: Sandra Chaparro, MD 
 
Telephone: 786-596-3505 
Fax:786-533-9570 
E-mail: sandrach@baptisthealth.net 
 
 
 
 
 
 
Co-Investigator  
 
Name:  Francisco Xavier Jimenez, MD 
 
 
 
 
Telephone: 305-666-4633 
 
 
 
 
Fax: 305-667-1675 
                                                    E-mail: francisj@smiamiheart.com 
 
Co-Investigator  
 
Name: Socrates V. Kakoulides, MD 
 
 
 
             Telephone: 786-204-4201 
 
 
 
 
Fax: 786-591-6001 
                                                    E-mail: socratesk@baptisthealth.net 
 
Co-Investigator  
 
Name: Raul Herrera, MD 
 
 
 
 
Telephone:786-596-3505 
 
 
 
 
Fax: 786-533-9570 
                                                    E-mail:  raulh@baptistheatlh.net 
 


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PROTOCOL AGREEMENT 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and providing 
complete and timely information, as outlined in the protocol.  It is understood that all 
information pertaining to the study will be held strictly confidential and that this confidentiality 
requirement applies to all study staff at this site. Furthermore, on behalf of the study staff and 
myself, I agree to maintain the procedures required to carry out the study in accordance with 
accepted GCP principles and to abide by the terms of this protocol. 
 
Protocol Title:  Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients with 
COVID-19 (COLHEART-19) 
 
Protocol Date:  06/05/2020 
 
 
 
 
Investigator Signature  
 
Date 
Sandra Chaparro, MD  
Print Name and Title 
Site # 
Single site 
 
Site Name 
Miami Cardiac and Vascular Institute, Baptist Hospital 
Address 
8900 North Kendall Drive, Miami, Florida 33176 
 
 
 
 
 
 
Phone Number 
Phone:   786-596-3505 
Fax:  786-533-9570   Email: sandrach@baptisthealth.net 
 


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Contents 
1 
BACKGROUND .................................................................................................................. 13 
1.1 
Overview of Non-Clinical Studies ................................................................................. 13 
1.2 
Overview of Clinical Studies ......................................................................................... 13 
2 
STUDY RATIONALE ......................................................................................................... 13 
2.1 
Risk / Benefit Assessment .............................................................................................. 14 
3 
STUDY OBJECTIVES ......................................................................................................... 14 
3.1 
Primary Objective .......................................................................................................... 14 
3.2 
Secondary Objectives ..................................................................................................... 14 
4 
STUDY DESIGN.................................................................................................................. 14 
4.1 
Study Overview .............................................................................................................. 14 
5 
CRITERIA FOR EVALUATION ........................................................................................ 15 
5.1 
Primary Efficacy Endpoint ............................................................................................. 15 
5.2 
Secondary Efficacy Endpoints ....................................................................................... 15 
5.3 
Safety Evaluations .......................................................................................................... 15 
6 
SUBJECT SELECTION ....................................................................................................... 15 
6.1 
Study Population ............................................................................................................ 15 
6.2 
Inclusion Criteria ............................................................................................................ 15 
6.3 
Exclusion Criteria ........................................................................................................... 16 
7 
CONCURRENT MEDICATIONS ....................................................................................... 16 
7.1 
Allowed Medications and Treatments............................................................................ 16 
8 
STUDY TREATMENTS ...................................................................................................... 16 
8.1 
Method of Assigning Subjects to Treatment Groups ..................................................... 16 
8.2 
Blinding .......................................................................................................................... 17 
8.3 
Formulation of Test ........................................................................................................ 17 
8.3.1 
Packaging and Labeling .......................................................................................... 17 
8.4 
Supply of Study Drug at the Site .................................................................................... 17 


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8.4.1 
Dosage/Dosage Regimen ........................................................................................ 17 
8.4.2 
Dispensing............................................................................................................... 18 
8.4.3 
Administration Instructions .................................................................................... 18 
8.5 
Supply of Study Drug at the Site .................................................................................... 19 
8.5.1 
Storage .................................................................................................................... 19 
8.6 
Study Drug Accountability............................................................................................. 19 
8.7 
Measures of Treatment Compliance .............................................................................. 19 
9 
STUDY PROCEDURES AND GUIDELINES .................................................................... 19 
9.1 
Clinical Assessments ...................................................................................................... 19 
9.1.1 
Concomitant Medications ....................................................................................... 19 
9.1.2 
Demographics ......................................................................................................... 19 
9.1.3 
Medical History ...................................................................................................... 20 
9.1.4 
Vital Signs ............................................................................................................... 20 
9.1.5 
Adverse Events ....................................................................................................... 20 
9.2 
Clinical Laboratory Measurements ................................................................................ 20 
9.2.1 
Inflammatory markers ............................................................................................. 20 
9.2.2 
Troponin and BNP .................................................................................................. 20 
10 Study Schema........................................................................................................................ 20 
10.1 Screening/Enrollment Day 1 (Baseline) ......................................................................... 20 
10.2 Days 3 and 7 (only if the patient remains hospitalized) ................................................. 21 
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ............................. 21 
11.1 Adverse Events ............................................................................................................... 21 
11.2 Serious Adverse Experiences (SAE) .............................................................................. 22 
11.2.1 Serious Adverse Experience Reporting .................................................................. 23 
11.3 Medical Monitoring........................................................................................................ 23 
12 DISCONTINUATION AND REPLACEMENT OF SUBJECTS ........................................ 23 
12.1 Early Discontinuation of Study Drug ............................................................................. 23 
12.3 Withdrawal of Subjects from the Study ......................................................................... 24 
12.4 Replacement of Subjects ................................................................................................ 24 
13 PROTOCOL VIOLATIONS ................................................................................................ 24 
14 STATISTICAL METHODS AND CONSIDERATIONS.................................................... 25 


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14.1 General Considerations .................................................................................................. 25 
14.2 Demographic and Baseline Characteristics .................................................................... 25 
14.3 Analysis of Primary Endpoint ........................................................................................ 25 
14.4 Analysis of Secondary Endpoints .................................................................................. 25 
• 
Secondary endpoint: Time (days) to the primary end point ........................................... 25 
14.6 Sample Size Justification ............................................................................................... 26 
15 DATA COLLECTION, RETENTION AND MONITORING ............................................ 26 
15.1 Data Collection Instruments ........................................................................................... 26 
15.2 Data Management Procedures ........................................................................................ 27 
15.3 Data Quality Control and Reporting .............................................................................. 27 
15.4 Archival of Data ............................................................................................................. 27 
15.5 Availability and Retention of Investigational Records .................................................. 27 
15.6 Monitoring ...................................................................................................................... 27 
15.7 Subject Confidentiality ................................................................................................... 28 
15.8 Protocol Amendments .................................................................................................... 28 
15.9 Institutional Review Boards and Independent Ethics Committees ................................ 28 
15.10 Informed Consent Form ................................................................................................. 29 
15.11 Publications .................................................................................................................... 29 
15.12 Investigator Responsibilities .......................................................................................... 29 
APPENDIX 1.  EXAMPLE OF SCHEDULE OF STUDY SCHEDULE ................................... 31 
PPENDIX 2.  EXAMPLE OF SUBJECT DIARY ....................................................................... 32 
References ..................................................................................................................................... 33 
 
 
 


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LIST OF ABBREVIATIONS 
 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
BNP 
aspartate aminotransferase 
brain naturetic peptide 
BUN 
CrCL 
blood urea nitrogen 
creatinine clearance 
CRP 
C-reactive protein 
DMC 
Data Monitoring Committee 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IL-6 
Interleukin-6 
IRB 
Institutional Review Board 
IV 
intravenous 
PI 
Principal Investigator 
SAE 
serious adverse experience 
 
 


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PROTOCOL SYNOPSIS 
TITLE 
Colchicine for the Treatment of Cardiac Injury in Hospitalized 
Patients with COVID-19 (COLHEART-19) 
 
 
 
SPONSOR/INVESTIGAT
OR 
Miami Cardiac and Vascular Institute(MCVI), Baptist Hospital 
Name: Sandra Chaparro, MD 
 
Telephone: 786-596-3505 
Fax: 
786-533-9570 
E-mail: sandrach@baptisthealth.net 
 
 
FUNDING 
ORGANIZATIONS 
 
Miami Cardiac and Vascular Institute 
NUMBER OF SITES 
Single Center Miami Cardiac and Vascular Institute, Baptist Hospital 
 
 
RATIONALE 
Myocardial injury has been described in up to 30% of COVID-19 infected 
patients, and portends a poor prognosis with currently no known treatment. 
Colchicine is a widely available, well-established, inexpensive, oral anti-
inflammatory agent that has been FDA approved for the treatment of 
inflammatory disorders including gout and familial Mediterranean Fever. 
Trials have also shown its benefit to prevent post-cardiotomy syndrome, to 
treat acute and recurrent pericarditis, and reduce cardiovascular events after 
myocardial infarction. We extrapolate based on these indications and studies 
that colchicine may also help improve outcomes in hospitalized COVID-19 
patients with evidence of cardiac injury.  
 
 
STUDY DESIGN 
Open-label (unblinded) randomization to treatment of colchicine plus 
current care per institution treating physicians vs. current care per institution 
treating physicians (control arm) 
 
 
PRIMARY OBJECTIVE 
To determine if Colchicine improves short-term outcomes in 
hospitalized COVID-19 patients with cardiac manifestations of 
disease. 
 
 
SECONDARY 
OBJECTIVES 
To assess if Colchicine reduces additional indices of cardiac injury in 
hospitalized COVID-19 patients with cardiac manifestations of disease  
 
 
NUMBER OF 
SUBJECTS 
75 
 
 
 
 


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SUBJECT SELECTION 
CRITERIA 
Inclusion Criteria: 
 
1. Men and Women ≥ 18 years of age 
2. Admission to hospital and respiratory status indicating oxygen 
therapy and/or mechanical ventilation. 
3. Cardiac injury (any of the following) 
a. Elevated troponin level 
b. Elevated BNP level 
c. New ischemic or arrhythmogenic ECG/telemetry changes  
d. New decrease in LVEF or new pericardial effusion on 
echocardiogram 
4. Able to provide informed consent  
Exclusion Criteria: 
 
1. Requirement of immediate need for mechanical ventilation and or 
circulatory support. 
2. Pregnancy, breastfeeding mothers, and women of childbearing age 
who are unable to use adequate contraception, which includes: 
a. Intrauterine devices (IUD), contraceptive implants, or tubal 
sterilization 
b. Hormone method with a barrier method 
c. Two barrier methods 
d. If a partner’s vasectomy is the chosen method of 
contraception, a hormone or barrier method must also be 
used in conjunction 
3. History of severe hematologic or neuromuscular disorder  
4. Co-administration of CYPA3A4 and P-glycoprotein transport 
inhibitor  
5. Severe renal impairment with concomitant hepatic impairment 
6. Concurrent use of colchicine and strong or P-glycoprotein inhibitor 
with renal or hepatic impairment  
 
 
TEST PRODUCT, DOSE, 
AND ROUTE OF 
ADMINISTRATION 
Colchicine dosing = 0.6 mg bid x 30 days 
Decrease dose to 0.3-0.6 mg daily or every other day in setting of 
gastrointestinal intolerance (nausea, diarrhea, emesis, abdominal discomfort) 
Decrease dose to 0.6 mg daily in the setting of weak or moderate CYP3A4 
inhibitor 
Decrease dose to 0.3 mg daily in the setting of strong CYP3A4, P-
glycoprotein inhibitors, or protease inhibitors 
Decrease dose to 0.3 mg daily in the setting of CKD stage ≥ 4 (CrCl ≤ 30 
ml/min) or liver failure (AST/ALT > 3x normal). 
Decrease dose to 0.6 mg every 14 days in patients with end stage renal 
disease (ESRD) or requiring dialysis 


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Route of Administration: oral 
 
CONTROL PRODUCT, 
DOSE AND ROUTE OF 
ADMINISTRATION 
Current care per treating physicians.  
DURATION OF 
SUBJECT 
PARTICIPATION AND 
DURATION OF STUDY 
Subjects will be on study for up to 90 days 
Treatment: 30 days 
• 
0.6 mg po bid x 30 days  
Follow-up: The follow-up period for a study participant will be 90 days. 
The total duration of the study is expected to be up to 12 months.  
CONCOMMITANT 
MEDICATIONS 
All dose adjustments per manufacturer guidelines.  
Dose adjustments to 0.6 mg po daily in the presence of a weak or moderate 
CYP3A4 inhibitor, and 0.3 mg in the setting of a strong CYPA3A4 
inhibitor, a P-glycoprotein inhibitor, or protease inhibitor.  
EFFICACY 
EVALUATIONS 
N/A 
PRIMARY ENDPOINT 
Composite of all-cause mortality, need for mechanical ventilation, or need 
for mechanical circulatory support (MCS) at 90 days 
SECONDARY 
ENDPOINTS 
● 
Time (days) to the primary end point  
● 
Individual components of the primary endpoint 
● 
Peak troponin level 
● 
Delta (change from baseline to peak) troponin level  
● 
Baseline BNP level  
● 
Inflammatory biomarkers (baseline and delta CRP and D-Dimer) 
● 
Hospital length of stay 
● 
90-day re-hospitalization 
 
SAFETY 
EVALUATIONS 
Reporting to regulatory bodies (MCVIIRB, FDA) will only be required for 
serious adverse events judged by the treating physician and study 
investigators to be potentially related to the administration of the study drug. 
All other adverse events will be reviewed by the study investigators and 
reported per FDA and IRB regulations.  
PLANNED INTERIM 
ANALYSES  
When approximately 25% of patients have completed the study, an interim 
analysis for safety will be conducted by the study investigators. Serious 
adverse events will be monitored by the study committee on an ongoing 
basis throughout the study. Serious adverse events will be reported to the 
Baptist Health South Florida (BHSF) IRB and FDA.  
Statistical Analysis Plan 
Appropriate data analysis sets will be defined. The intent-to-treat (ITT) 
analysis set will be used in the analyses of the primary and secondary 
endpoints. The ITT analysis set will include data from all subjects who are 
randomized, with study drug assignment designated to initial randomization, 
regardless of whether subjects receive any study drug or receive a different 
regimen from that to which they were randomized. A safety analysis set will 
comprise data from subjects who receive at least one dose of study drug, 
with treatment regimen assignment (Colchicine or control) designated 


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according to the actual regimen received. Per-Protocol (PP) analysis set will 
be used for sensitivity analysis for the primary and secondary endpoints. 
 
The primary endpoint is the composite event rate of all-cause mortality, 
need for mechanical ventilation, or need for MCS at 90 days. Fisher’s exact 
test will be used to compare the proportion of patients achieve the composite 
event between two study arms. For each arm, the proportion of patients 
achieve the composite event at 90 days will be calculated, along with the 
95% exact confidence interval. 
 
For the secondary endpoints: 
1) Time (days) to the primary end point: Kaplan Meier estimates will be 
provided for each study arm and presented graphically. Log-rank test will be 
used to compare the event curves between study arms. Hazard ratios and 
corresponding 95% CIs will be presented. 
2) Individual components of the primary endpoint, and 90-day re-
hospitalization:  
For each of these, Fisher’s exact test will be used to compare the event rate 
between two study arms. For each arm, the proportion of patients achieve 
the composite event at 90 days will be calculated, along with the 95% exact 
confidence interval. 
3) Peak troponin level, Delta (change from baseline to peak) troponin level, 
Baseline BNP level, Inflammatory biomarkers (baseline and delta CRP and 
D-Dimer), Hospital length of stay: For each of these, unpaired t test or 
Wilcoxon rank rum test will be used to compare the two study arms. For 
each arm, descriptive statistics such as mean, median, standard deviation, 
IQR will be summarized and reported. 
 
Safety Analysis: Safety profile including AE and SAEs will be reported. 
Simple descriptive statistics will be used to summarize toxicities in terms of 
type, severity and minimum or maximum values for laboratory measures, 
time of onset, duration, and reversibility or outcome. Tables will be created 
to summarize these toxicities and side effects. Safety Analyses will be 
performed on Safety Analysis Set. 
Rationale for Number of 
Subjects 
This is an open-label, randomized controlled study with the primary 
objective to determine if Colchicine improves short-term outcomes in 
hospitalized COVID-19 patients with cardiac manifestations of disease. 
Patients will be randomized in 1:1 ratio to receive colchicine 0.6 mg po BID 
x 30 days plus current care per treating physicians versus current care per 
physicians alone (control arm). The primary endpoint is the composite event 
rate of all-cause mortality, need for mechanical ventilation, or need for MCS 
at 90 days. Sixty-eight patients per arm are needed to achieve 80% power to 
detect 20% difference in this composite event rate between the two groups, 
assuming 10% in the treatment group and 30% event rate in the control 
group, with a two-sided Fisher’s exact test at a 0.05 significance level. 


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Accounting for 9% attrition rate, a total of 150 subjects (n=75 per arm) will 
be enrolled. 
 
 


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1 BACKGROUND 
SARS-CoV-2, a novel betacoronavirus that causes a new human disease referred to as COVID-
19, has led to a worldwide pandemic affecting over a million people to date. Of those patients 
infected, up to 80% have only mild symptoms that resolve spontaneously.1 Patients that develop 
more severe symptoms are generally hospitalized and can experience acute respiratory distress, 
cardiac injury or shock, renal failure, and ultimately death.2 Patients with underlying 
cardiovascular disease and elevated cardiac biomarkers are at increased risk with mortality 
reaching up to 70%.3,4 While several mechanisms have been postulated for how SARS-CoV-2 
may damage the heart, it is plausible that the indirect damage from innate, cellular, or humoral 
immune response including ‘cytokine storm’ may play a pivotal role.5 We hypothesize that 
Colchicine may attenuate the cardiac injury observed in later stages of COVID-19 through 
downregulation of the inflammatory and the host adaptive immune response.  
1.1 
Overview of Non-Clinical Studies 
Colchicine is a microtubule inhibitor and anti-inflammatory agent.6 It has been suggested that the 
inhibition of the microtubule polymerization interferes with lipopolysaccharides resulting in the down-
regulation of interleukin (IL) - 6, IL-1, GM-CSF, and the NLRP3 inflammasome.7 Study of the COVID-
19 inflammatory cascade shows CD4+T lymphocytes rapidly activated to pathogenic T helper (Th1) cells 
that generate granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as cytokines that 
induces inflammatory CD14+ and CD16+ monocytes with high expression of IL-6.8 Clinically, there is a 
marked increase in C-reactive protein (CRP), aspartate transaminases (AST), alanine transaminases 
(ALT), and decreased lymphocytes, reflecting the pro-inflammatory state.9 Plasma troponin levels have 
been shown to be associated with a significant increase in CRP levels, which is associated with increased 
cardiac injury and mortality.10   
 
1.2 
Overview of Clinical Studies 
Colchicine has been FDA approved for gout and familial Mediterranean fever.7 Several studies have 
shown benefit in acute and recurrent pericarditis and post-cardiotomy, and more recently post-myocardial 
infarction.11-15 Microtubule inhibition may also interfere with the viral replication machinery by 
disrupting the cellular cytoskeleton, and colchicine in viral myocarditis has been shown to improve left 
ventricular ejection fraction after treatment.16,17 We extrapolate from these studies, that colchicine may 
benefit hospitalized COVID-19 patients with evidence of cardiac injury.  
2 STUDY RATIONALE 
Cardiac injury has been described in up to 30% of COVID-19 infected patients, and portends a poor 
prognosis with currently no known treatment. Colchicine is a widely available, well-established, 
inexpensive, oral anti-inflammatory agent that may help reduce myocardial injury in hospitalized patients 
with COVID-19. 


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2.1 
Risk / Benefit Assessment 
The most common adverse event with colchicine is gastrointestinal intolerance (diarrhea, emesis, nausea, 
abdominal discomfort) leading to discontinuation in 5-8% of patients. Myelosuppression and aplastic 
anemia are rare at the proposed dosages. Neuromuscular toxicity has been documented at an increased 
risk with drugs inhibitor P-glycoprotein. Taking into account there is no known treatment to prevent or 
treat myocardial injury in COVID-19 patients, we feel the benefits of the medication outweigh its 
relatively small risks.  
3 STUDY OBJECTIVES 
3.1 
Primary Objective 
The primary objective is to assess if Colchicine improves short-term outcomes in hospitalized COVID-19 
patients with cardiac manifestations of disease. The primary endpoint is the composite of all-cause 
mortality, need for mechanical ventilation, or need for MCS at 90 days. 
3.2 
Secondary Objectives 
• 
To assess whether or not Colchicine reduces additional indices of cardiac injury in 
hospitalized COVID-19 patients with cardiac manifestations of disease  
 
4 
STUDY DESIGN 
4.1 
Study Overview 
We propose a single center, open-label (unblinded) randomized controlled trial. Patients will be 
randomized in a 1:1 ratio to receive Colchicine 0.6 mg po BID x 30 days plus current care per treating 
physicians versus current care per treating physicians alone (control arm). Importantly, this trial design 
allows for patients in either study arm to receive other investigational drugs for COVID-19 as new 
science emerges. The primary endpoint is the composite of all-cause mortality, need for mechanical 
ventilation, or need for MCS at 90 days. Secondary endpoints include time (days) to the primary end 
point, the individual components of the primary endpoint, other markers of cardiac injury (peak and delta 
troponin and baseline BNP), inflammatory biomarkers (baseline and delta CRP and D-Dimer levels), and 
90-day re-hospitalization. The treatment duration will be 30 days with a 90-day follow-up period. 
Inclusions/exclusion criteria will be reviewed to determine patient eligibility.   
The method of permuted block randomization will be used. Permuted block sizes are not disclosed to the 
study personnel to minimize the likelihood of their being able to predict the next randomization 
assignment in the series. Eligible participants will be assigned in 1:1 ratio to an unblinded fashion to one 
of the following dosing regimens: 
● Colchicine at 0.6 mg po bid for 30 days 
● Dose reductions in the setting of concomitant CYP3A4 and P-glycoprotein inhibitors, 
in the setting of severe renal and hepatic disease, or if GI symptoms occur. Total 
duration of subject participation will be 30 days treatment followed by a 90 days 
follow-up period.  Total duration of the study is expected to be 12 months. 


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5 CRITERIA FOR EVALUATION 
5.1 
Primary Efficacy Endpoint 
The primary endpoint is the composite of all-cause mortality, need for mechanical ventilation, or need for 
MCS at 90 days.   
5.2 
Secondary Efficacy Endpoints 
Secondary endpoints include: time (days) to the primary end point, the individual components of the 
primary endpoint, re-hospitalization rates at 90 days, markers of cardiac injury (peak troponin, delta 
troponin, baseline BNP levels, inflammatory biomarkers (baseline and delta CRP and D-Dimer levels).  
5.3 
Safety Evaluations 
Several adverse events are known with colchicine and will be monitored and include: 
• 
Blood dyscrasia such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, 
pancytopenia and aplastic anemia have been reported with colchicine and will be monitored 
• 
Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been  reported with chronic 
treatment in therapeutic doses. Patients with renal dysfunction and elderly patients are at increased 
risk, and will be monitored more closely. 
• 
The most common adverse reactions reported in clinical trials with colchicine were gastrointestinal 
trace adverse effects, occurring in up to 5-8% of patients given therapeutic doses. Typical 
symptoms include cramping, nausea, diarrhea, abdominal pain, and emesis. These events will 
warrant dose-reduction and close monitoring.  
 
6 SUBJECT SELECTION 
6.1 
Study Population 
Subjects with a diagnosis of COVID-19 who meet the inclusion and exclusion criteria will be eligible for 
participation in this study.   
6.2 
Inclusion Criteria 
1. 
Age ≥ 18 years of age. 
2. 
Documentation of SARS-CoV2-19 infection 
3. 
Admission to hospital and respiratory status indicating oxygen therapy and/or mechanical 
ventilation. 
4. 
Cardiac injury (any of the following): 
a. Elevated troponin level 
b. Elevated BNP level 
c. New ischemic or arrhythmogenic changes on ECG/telemetry 


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d. New drop in LVEF or pericardial effusion on echocardiogram 
5. 
Written informed consent (and assent when applicable) obtained from subject or subject’s legal 
representative and ability for subject to comply with the requirements of the study. 
6.3 
Exclusion Criteria 
 
1. Requirement of immediate need for mechanical ventilation and or circulatory support. 
2. 
Pregnancy, breastfeeding mothers, or women of childbearing age unable to take adequate birth 
control during the duration of the study, which includes: 
a) Intrauterine devices (IUD), contraceptive implants, or tubal sterilization 
b) Hormone method with a barrier method 
c) Two barrier methods 
d) If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method 
must also be used in conjunction 
2. 
History of severe hematologic disease or neuromuscular disorders 
3. 
Co-administration of CYP3A4 and P-glycoprotein inhibitor (i.e. Clarithromycin) 
4. Severe renal impairment with concomitant hepatic impairment. 
5. Concurrent use of colchicine and strong CYP3A4 or P-gp inhibitors in patients with renal or 
hepatic impairment 
 
7 CONCURRENT MEDICATIONS 
Patients are randomized 1:1 to colchicine 0.6 mg bid x 30 days to colchicine plus current care per treating 
physicians versus current care per treating physicians alone (control arm). This trial design allows for 
patients in either study arm to receive other investigational drugs for COVID-19 in addition to colchicine 
as new science emerges.  
7.1 
Allowed Medications and Treatments 
Standard therapy for colchicine is allowed except for treatments noted in the exclusion criteria described 
above and as noted in the prohibited medications section below.   
 
8 STUDY TREATMENTS 
8.1 
Method of Assigning Subjects to Treatment Groups 
Eligible participants will include hospitalized patients ≥ 18 years-old with confirmed COVID-19 
infection and objective evidence of cardiac injury (elevated troponin level, elevated BNP level, new 
ECG/telemetry changes consistent with ischemia or arrhythmia, or new drop in LVEF or new pericardial 
effusion on echocardiogram). Patients will be randomized in an unblinded 1:1 ratio to receive colchicine 


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0.6 mg po BID x 30 days plus current care per treating physicians versus current care per physicians 
alone (control arm).  
8.2 
Blinding 
Study subjects are randomly assigned to colchicine plus current care per physicians versus current care 
per physicians (control arm).  Neither the patient nor the treatment team or study investigators will be 
blinded. This trial design allows colchicine to be added to other investigational drugs for COVID-19 as 
new data and studies are available. 
8.3 
Formulation of Test  
Colchicine is an alkaloid chemically described as (S)N- (5,6,7,9-tetrahydro- 1,2,3, 10-tetramethoxy-9-
oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of C22H25NO6 and a molecular 
weight of 399.4. The structural formula of colchicine is given below.  
Colchicine occurs as a pale yellow powder that is soluble in water.  
COLCRYS (colchicine, USP) tablets are supplied for oral administration as purple, film- coated, capsule-
shaped tablets (0.1575” × 0.3030”), debossed with “AR 374” on one side and scored on the other, 
containing 0.6 mg of the active ingredient colchicine USP. Inactive ingredients: carnauba wax, FD&C 
blue #2, FD&C red #40, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline 
cellulose, polydextrose, polyethylene glycol, pregelatinized starch, sodium starch glycolate, titanium 
dioxide and triacetin.  
8.3.1 Packaging and Labeling 
Colchicine used for investigational purposes in COVID-19 patients will be labeled clearly and 
administered separately from normal medications. On discharge, a bottle clearly labeling the medication 
as investigational will be dispensed to the patient.  
8.4 
Supply of Study Drug at the Site 
Colchicine will be stored per manufacturer guidelines, dispensed, and accounted for by the 
Baptist Hospital investigational pharmacy.  
8.4.1 Dosage/Dosage Regimen 
Colchicine will be administered at 0.6 mg po every 12 hours. Patients under the age of 18, pregnant 
breastfeeding, or women of childbearing age who are unable to take 2 forms of contraception will be 
excluded from the study. All dosage adjustments below per manufacturer recommendations: 
1. Renal impairment: 
a. Colchicine is excreted in the urine in healthy subjects, and clearance is decreased in 
patients with impaired renal function.  
b. For patient with CrCL ≤ 30, the dose will be adjusted to 0.3 mg daily 
c. In patients with end-stage renal disease or undergoing dialysis the dose will be reduced to 
0.6 mg every 14 days 


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2. Hepatic impairment 
a. The clearance of colchicine may be significantly reduced and plasma half-life prolonged 
in patient’s hepatic impairment 
b. Dose will be adjusted to 0.3 mg daily for severe hepatic dysfunction (AST/ALT ≥ 3x 
baseline).  
3. Dose adjustments for concomitant medications 
a. Strong CYP3A4 inhibitors (Atazanavir, indinavir, itraconazole, ketoconazole, nefazodone, 
nelfinavir, ritonavir, saquinavir, telithromycin 
i. 
Dose reduction to 0.3 mg once daily 
b. Moderate CYP3A4 inhibitors (Amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, 
fosamprenavir, grapefruit juice, verapamil) 
i. 
Dose reduction to 0.6 mg once daily 
c. P-glycoprotein inhibitors (Cyclosporin, ranolazine) 
i. 
Dose reduction to 0.3 mg once daily 
d. Protease inhibitors (atazanavir sulfate, darunavir) 
i. 
Dose reduction to 0.3 mg once daily 
ii. 
Colchicine should not be dispensed concomitantly with protease inhibitor in the setting of 
renal or hepatic impairment 
e. Strong CYP3A4 inhibitor and P-Glycoprotein inhibitor 
i. 
Colchicine should not be administered in the setting of both a CYP3A4 and P-
Glycoprotein inhibitor such as Clarithromycin 
 
Colchicine interacts with the P-glycoprotein transporter, and the CYP3A4 enzyme involved in drug and 
toxin metabolism. Fatal drug interactions have occurred when colchicine was taken with other drugs that 
inhibit P-glycoprotein and CYP3A4.    
Avoid taking macrolide antibiotics (erythromycin or clarithromycin), ketoconazole or cyclosporine,    
Avoid taking atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, 
grapefruit juice and atorvastatin/rosuvastatin.  
8.4.2 Dispensing 
Colchicine will be dispensed by the Baptist Hospital investigational pharmacy.  
8.4.3 Administration Instructions  
Colchicine will be prepared per the Baptist Hospital investigational pharmacy protocol. The medication 
will be dispensed by the investigational pharmacy as single doses to study participants while admitted. 
The medication will be dispensed by the Baptist Hospital Pharmacy as a completed study course-supply 
and will be taken as a single doses by study participatns while admitted.  On discharge, the study drug 
will be dispensed with clear instructions to complete a 30-day course. Colchicine will be prepared per 
the Baptist Hospital investigational pharmacy protocol. On discharge, the study drug will be 
dispensed with clear instructions to complete a 30-day course. 
 


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8.5 
Supply of Study Drug at the Site 
Study drug will be supplied by the Baptist Hospital investigational pharmacy through hospital 
protocol.  
8.5.1 Storage 
Study drug should be stored by the study site at controlled room temperature, 15 to 30ºC (59 to 86ºF). If 
the temperature of study drug storage in the clinic/pharmacy exceeds or falls below this range, this should 
be captured as a deviation. Subjects will be instructed to store the medication in original packaging (foil 
pouch and protected from light) at room temperature according to the instructions outlined on the Drug 
Administration Instructions. 
8.6 
Study Drug Accountability 
An accurate and current accounting of the dispensing and return of study drug for each subject will be 
maintained on an ongoing basis by a member of the study site staff.  The number of study drug dispensed 
and returned by the subject will be recorded on the Investigational Drug Accountability Record.  The 
study monitor will verify these documents throughout the course of the study. 
8.7 
Measures of Treatment Compliance 
Subjects will be asked to keep a patient diary noting the day and date they take their study drug and any 
symptoms or adverse events. If the patient misses a dose, he/she will be instructed to document the event, 
but continue treatment with the next scheduled dose. Subjects will be instructed to not make up the dose. 
Appendix 2 
9 STUDY PROCEDURES AND GUIDELINES 
A Schedule of Events representing the required testing procedures to be performed for the duration of the 
study is diagrammed in Appendix 1. 
Prior to conducting any study-related activities, written informed consent and the Health Insurance 
Portability and Accountability Act (HIPAA) authorization must be signed and dated by the subject or 
subject’s legal representative.  If appropriate, assent must also be obtained prior to conducting any study-
related activities. 
9.1 
Clinical Assessments 
9.1.1 Concomitant Medications 
All concomitant medication and concurrent therapies will be documented throughout the study. Dose, 
route, unit frequency of administration, and indication for administration and dates of medication will be 
captured. 
9.1.2 Demographics  
Demographic information (age, sex, race) will be recorded at enrollment. 


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9.1.3 Medical History  
Relevant medical history, including history of current disease, other pertinent respiratory history, and 
information regarding underlying cardiovascular disease and risk factors for cardiovascular disease will 
be recorded at screening. 
9.1.4 Vital Signs 
Body temperature, blood pressure, pulse, and respiratory rate will be performed and recorded. 
9.1.5 Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. 
Duration (start and stop dates and times), severity/grade, outcome, treatment and relation to 
study drug will be recorded on the case report form (CRF). 
9.2 
Clinical Laboratory Measurements  
9.2.1 Inflammatory markers 
Blood will be obtained and sent to the clinical lab for serum C-reactive protein (CRP) and D-Dimer on 
day 1 (baseline); days 3 and 7 only if the patient remains hospitalized (will avoid as an outpatient to 
minimize risk of COVID-19 transmission to health care workers and limit PPE use as well as to adhere to 
2-week quarantine guidelines for COVID-19+ patients. Additional labs may be checked by the treating 
physicians as part of clinical care. Labs for a specific time period can be obtained within ±1 day of the 
assigned time.   
9.2.2 Troponin and BNP 
Blood will be obtained and sent to the clinical lab for serum troponin and BNP on days 1 (baseline); days 
3 and 7 only if the patient remains hospitalized. Additional labs may be checked by the treating 
physicians as part of clinical care. Labs for a specific time period can be obtained within ±1 day of the 
assigned time.   
10   STUDY SCHEMA 
10.1 
Screening/Enrollment Day 1 (Baseline) 
1. 
Assess potential subjects admitted to Baptist Hospital based on inclusion/exclusion criteria 
2. 
For patients who meet inclusion/exclusion criteria, the investigator team will review the study with 
the subject (or subject’s legal representative) in person or over the phone and obtain 
written/telephone informed consent and HIPAA authorization and assent, if appropriate. 
3. 
Assign the subject a unique screening number. 
4. 
Record demographic data. 
5. 
Record medical history. 
6. 
Record concomitant medications. 
7. 
Perform and record vital signs. 
8. 
Record results of blood pressure testing. 


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9. 
Obtain blood samples for baseline troponin, BNP, CRP, and D-dimer levels 
10. 
Obtain baseline echocardiogram, , which can be obtained within ±3 day of the assigned time 
11. 
Randomize subject, dispense study drug if randomized to the colchicine arm 
12. 
Calculate the WHO Scale and record. 
10.2 
Days 3 and 7 (only if the patient remains hospitalized) 
1. 
Record any adverse events and/or review subject diary for symptoms, adverse events, and 
medication adherence. 
2. 
Concomitant medications reviewed. 
3. 
Obtain blood sample for clinical laboratory tests (troponin, BNP, D-Dimer, CRP) 
 
10.3 
Day 30  and Day  90  
 
At   30 Days record the WHO Ordinal Scale Score and then calculate Delta Score by subtracting 
30 days score minus baseline. Obtain information via telephonic interview and review of 
electronic medical records.  
 
  
AT 90 Days record any adverse events and/or review subject diary for symptoms, adverse                
events, and hospitalizations via telephonic interview and review of electronic medical records. 
The COLHEART-19 Day Questionnaire will be used which includes the WHO Ordinal Scale in 
order to assess the Primary Outcome. 
 
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
11.1 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a patient 
administered a pharmaceutical product and that does not necessarily have a causal relationship with the 
treatment.  An AE is therefore any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom or disease temporally associated with the administration of an investigational product, 
whether or not related to that investigational product.  An unexpected AE is one of a type not identified in 
nature, severity, or frequency in the current Investigator’s Brochure or of greater severity or frequency 
than expected based on the information in the Investigator’s Brochure. 
The Investigator will probe, via discussion with the subject, for the occurrence of AEs during each subject 
visit and record the information in the site’s source documents.  Adverse events will be recorded in the 
patient CRF.  Adverse events will be described by duration (start and stop dates and times), severity, 
outcome, treatment and relation to study drug, or if unrelated, the cause. 
AE Severity 
The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 
should be used to assess and grade AE severity, including laboratory abnormalities judged to be clinically 
significant. The modified criteria can be found in the study manual.  If the experience is not covered in 


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the modified criteria, the guidelines shown in Table 1 below should be used to grade severity.  It should 
be pointed out that the term “severe” is a measure of intensity and that a severe AE is not necessarily 
serious. 
Table 1.  AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
Transient or mild discomfort; no limitation in activity; no medical 
intervention or therapy required. The subject may be aware of the sign 
or symptom but tolerates it reasonably well. 
Moderate (2) 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. 
Severe (3) 
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible. 
Life-threatening (4) 
The subject is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe. 
 
AE Relationship to Study Drug 
The relationship of an AE to the study drug should be assessed using the following the guidelines in 
Table 2. 
Table 2.  AE Relationship to Study Drug 
Relationship 
to Drug 
Comment 
Definitely 
Previously known toxicity of agent; or an event that follows a reasonable temporal 
sequence from administration of the drug; that follows a known or expected response 
pattern to the suspected drug; that is confirmed by stopping or reducing the dosage 
of the drug; and that is not explained by any other reasonable hypothesis. 
Probably 
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that is 
confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be 
explained by the known characteristics of the subject’s clinical state or by other 
interventions. 
Possibly 
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but 
that could readily have been produced by a number of other factors. 
Unrelated 
An event that can be determined with certainty to have no relationship to the study 
drug. 
11.2 
Serious Adverse Experiences (SAE) 
An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: 
● death 
● a life-threatening adverse experience 
● inpatient hospitalization or prolongation of existing hospitalization 


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● a persistent or significant disability/incapacity 
● a congenital anomaly/birth defect  
Other important medical events may also be considered an SAE when, based on appropriate medical 
judgment, they jeopardize the subject or require intervention to prevent one of the outcomes listed.  
 
11.2.1 Serious Adverse Experience Reporting 
All SAEs that occur (whether or not related to study drug) will be reported per Baptist Health South 
Florida IRB guidelines and policy.   The collection period for all SAEs will begin after informed consent 
is obtained and end after procedures for the final study visit have been completed. 
In accordance with the standard operating procedures and policies of the local Institutional Review Board 
(IRB)/), the site investigator will report SAEs to the IRB and FDA.   
11.3 
Medical Monitoring 
Sandra Chaparro, MD should be contacted directly at these numbers to report medical concerns or 
questions regarding safety. 
 
 
Name: Sandra Chaparro, MD 
Phone:  786-596-3505 or 786-204-4201 
  
12 DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
12.1 
Early Discontinuation of Study Drug  
A subject may be discontinued from study treatment at any time if the subject, the sponsor/investigator, or 
study team determines that it is not in the subject’s best interest to continue.  The following is a list of 
possible reasons for study treatment discontinuation:  
● Subject withdrawal of consent (or assent) 
● Subject is not adherent with study procedures 
● Adverse event that in the opinion of the investigator would be in the best interest of the 
subject to discontinue study treatment 
● Protocol violation requiring discontinuation of study treatment 
● Loss to follow-up 
● Sponsor request for early termination of study 
● Positive pregnancy test or women of childbearing age who can no longer take adequate 
contraception, which includes: 
● Intrauterine devices (IUD), contraceptive implants, or tubal sterilization 
● Hormone method with a barrier method 
● Two barrier methods 


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● If a partner’s vasectomy is the chosen method of contraception, a hormone or 
 
barrier method must also be used in conjunction  
If a subject is withdrawn from treatment due to an adverse event, the subject will be followed and treated 
by the Investigator until the abnormal parameter or symptom has resolved or stabilized.   
All subjects are free to withdraw from participation at any time, for any reason, specified or unspecified, 
and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject withdrawals.  The 
reason for the subject’s withdrawal from the study will be recorded in the study. 
12.3 
Withdrawal of Subjects from the Study 
A subject may be withdrawn from the study at any time if the subject, the sponsor/investigator, or the 
study team determines that it is not in the subject’s best interest to continue.   
All subjects are free to withdraw from participation at any time, for any reason, specified or unspecified, 
and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject withdrawals.  The 
reason for the subject’s withdrawal from the study will be specified in the subject’s source 
documents.  As noted above, subjects who discontinue study treatment early (i.e., they withdraw prior to 
the 30-day visit) should have an early discontinuation visit if they have been discharged from the hospital. 
Refer to Section 10 for early termination procedures.  Subjects who withdraw after discharge from the 
hospital but prior to day 30 should be encouraged to come in for a final laboratory and imaging visit. 
12.4 
Replacement of Subjects 
Subjects who withdraw from the study treatment will not be replaced.   
Subjects who withdraw from the study itself will not be replaced.   
 
13 PROTOCOL VIOLATIONS 
A protocol violation occurs when the subject, investigator, or Sponsor fails to adhere to significant 
protocol requirements affecting the inclusion, exclusion, subject safety and primary endpoint criteria.  
Protocol violations for this study include, but are not limited to, the following: 
● Failure to meet inclusion/exclusion criteria 
● Use of a prohibited concomitant medication 
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a protocol violation. 
The Investigator will determine if a protocol violation will result in withdrawal of a subject. 
When a protocol violation occurs, it will be discussed with the investigator and a Protocol Violation Form 
detailing the violation will be generated. This form will be signed by the Investigator. tThe form will be 
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14 STATISTICAL METHODS AND CONSIDERATIONS 
14.1 
General Considerations 
Data collected in this study will be presented using summary tables and patient data listings. Continuous 
variables will be summarized using descriptive statistics, specifically the mean, median, standard 
deviation, minimum, and maximum. Categorical variables will be summarized by frequencies and 
percentages. \Data Sets Analyzed 
• Intent-to-Treat (ITT) Analysis Set 
The ITT analysis set includes all subjects who are randomized regardless of whether subjects 
receive any study drug(s), or receive a different regimen from the regimen they were randomized 
to. Treatment assignment will be designated according to randomization. This analysis set will 
be used in the analysis for the primary endpoint and the secondary endpoint. 
 
• Per-Protocol (PP) Analysis Set 
The PP analysis set includes data from subjects in the ITT analysis set who meet the general 
criteria defining the target population for this study, are adherent to the protocol, are compliant 
with study drug treatment, and are evaluable for relevant efficacy endpoints. Treatment 
assignment will be designated according to the actual treatment received. The PP analysis set 
will be used in sensitivity analyses of the primary and secondary endpoints. 
 
• Safety Analysis Set 
A safety analysis set will include data from subjects who receive at least one dose of study 
treatment, with treatment assignments designated according to the actual treatment received. 
This analysis set will be used in the analyses of safety variables as well as study treatment 
administration. 
14.2 
Demographic and Baseline Characteristics 
The following demographic variables at screening will be included: race, sex, age, BMI, medication 
history, co-morbidities including cardiovascular disease and risk factors for cardiovascular disease.   
14.3 
Analysis of Primary Endpoint 
The primary endpoint is the composite event rate of all-cause mortality, need for mechanical ventilation, 
or need for MCS at 90 days. Fisher’s exact test will be used to compare the proportion of patients achieve 
the composite event between two study arms. For each arm, the proportion of patients achieve the 
composite event at 90 days will be calculated, along with the 95% exact confidence interval. 
14.4 
Analysis of Secondary Endpoints 
Secondary endpoint: Time (days) to the primary end point Kaplan Meier estimates will be provided 
for each study arm and presented graphically. Log-rank test will be used to compare the event curves 


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between study arms. Hazard ratios and corresponding 95% CIs (as calculated using a Cox proportional 
hazards regression model) will be presented. 
• Secondary endpoints: Individual components of the primary endpoint. For each of these, 
Fisher’s exact test will be used to compare the event rate between two study arms. For 
each arm, the proportion of patients achieve the composite event at 90 days will be 
calculated, along with the 95% exact confidence interval. 
• 
Secondary endpoints: Peak troponin level, Delta (change from baseline to peak) troponin level, 
baseline BNP level, Inflammatory biomarkers (baseline and delta CRP and D-Dimer), Hospital 
length of stay 
• 
For each of these, unpaired t test or Wilcoxon rank rum test will be used to compare the two study 
arms. For each arm, descriptive statistics such as mean, median, standard deviation, IQR will be 
summarized and reported. 
14.5 Analysis of Safety 
Safety profile including AE and SAEs will be reported. Simple descriptive statistics will be used 
to summarize toxicities in terms of type, severity and minimum or maximum values for 
laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created 
to summarize these toxicities and side effects. Safety Analyses will be performed on Safety 
Analysis Set. 
14.6 Sample Size Justification 
This is an open-label, randomized controlled study with the primary objective to determine if Colchicine 
improves short-term outcomes in hospitalized COVID-19 patients with cardiac manifestations of disease. 
Patients will be randomized in 1:1 ratio to receive colchicine 0.6 mg po BID x 30 days plus current care 
per treating physicians versus current care per physicians alone (control arm). The primary endpoint is the 
composite event rate of all-cause mortality, need for mechanical ventilation, or need for mechanical 
circulatory support (MCS) at 90 days. 68 patients per arm are needed to achieve 80% power to detect 
20% difference in this composite event rate between the two groups, assuming 10% in the treatment 
group and 30% event rate in the control group (based on recent published studies18,19,20), with a two-sided 
Fisher’s exact test at a 0.05 significance level. Accounting for 9% attrition rate, a total of 150 subjects 
(n=75 per arm) will be enrolled. 
As our site will be enrolling about 75 patients in the trial, we are aiming to achieve the calculated 
statistical sample size by sharing our de-identified data results with the UCLA (University of California 
Los Angeles) Medical Center in California, conducting this same trial in the Los Angeles area with this 
same identical clinical study protocol. Our IND submission does cross-reference the UCLA IND already 
approved by the FDA. 
.  
15 DATA COLLECTION, RETENTION AND MONITORING 
15.1 
Data Collection Instruments 
The Investigator will prepare and maintain adequate and accurate source documents designed to record all 
observations and other pertinent data for each subject treated with the study drug.   


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Study personnel will enter data from source documents corresponding to each subject into the protocol-
specific electronic Case Report Form (eCRF) OR paper CRF when the information corresponding to that 
visit is available.  Subjects will not be identified by name in the study database or on any study 
documents to be collected by the Sponsor (or designee), but will be identified by a subject number. 
The Investigator is responsible for all information collected on subjects enrolled in this study.  All data 
collected during the course of this study must be reviewed and verified for completeness and accuracy by 
the Investigator.  A copy of the CRF will remain at the Investigator’s site at the completion of the study. 
15.2 
Data Management Procedures 
The data will be entered into a secure, de-identified, database.  The study coordinators will be responsible 
for data processing, in accordance with procedural documentation.  Database lock will occur once quality 
assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good computing practices 
meeting FDA guidelines for the handling and analysis of data for clinical trials. 
15.3 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation checks 
will be implemented and applied to the database on a regular basis. The study database will be updated in 
accordance with the resolved queries.  All changes to the study database will be documented. 
15.4 
Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; appropriate 
backup copies of the database and related software files will be maintained.  Databases are backed up by 
the database administrator in conjunction with any updates or changes to the database.   
At critical junctures of the protocol (e.g., production of interim reports and final reports), data for analysis 
is locked and cleaned per established procedures. 
15.5 
Availability and Retention of Investigational Records 
The Sponsor/Investigator must make study data accessible to the monitor, IRB/ and Regulatory Agency 
(e.g., FDA) inspectors upon request.  A file for each subject must be maintained that includes the signed 
Informed Consent, HIPAA Authorization and Assent Form and copies of all source documentation related 
to that subject.  The Investigator must ensure the reliability and availability of source documents from 
which the information on the CRF was derived. 
All study documents (patient files, signed informed consent forms, copies of CRFs, Study File Notebook, 
etc.) must be kept secured for a period of two years following marketing of the investigational product or 
for two years after centers have been notified that the IND has been discontinued.  There may be other 
circumstances for which the Sponsor/Investigator is required to maintain study records. 
15.6 
Monitoring 
Monitoring visits will be conducted according to the U.S. CFR Title 21 Parts 50, 56, and 312 and ICH 
Guidelines for GCP (E6).    By signing this protocol, the Sponsor/Investigator grants permission to the 


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appropriate regulatory authorities to conduct on-site monitoring and/or auditing of all appropriate study 
documentation. 
15.7 
Subject Confidentiality 
In order to maintain subject confidentiality, only a subject number will identify all study subjects on 
CRFs and other documentation.  
 
 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
The study will be conducted according to the Declaration of Helsinki, Protection of Human Volunteers 
(21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical Investigators (21 
CFR 312). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records will be 
identified by a coded number and initials only.  All study records will be kept in a locked file cabinet and 
code sheets linking a patient’s name to a patient identification number will be stored separately in another 
locked file cabinet.  Clinical information will not be released without written permission of the subject, 
except as necessary for monitoring by the FDA.  The Investigator must also comply with all applicable 
privacy regulations (e.g., Health Insurance Portability and Accountability Act of 1996, EU Data 
Protection Directive 95/46/EC). 
15.8 
Protocol Amendments 
Any amendment to the protocol will be written by the Sponsor/Investigator.  Protocol amendments cannot 
be implemented without prior written IRB approval except as necessary to eliminate immediate safety 
hazards to patients.  A protocol amendment intended to eliminate an apparent immediate hazard to 
patients may be implemented immediately, provided the IRBs are notified within five working days. 
15.9 
Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the IRB.  Serious adverse experiences 
regardless of causality will be reported to the IRB in accordance with the standard operating procedures 
and policies of the IRB, and the Investigator will keep the IRB informed as to the progress of the study.  
The Investigator will obtain assurance of IRB compliance with regulations. 
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, protocol 
amendments, Investigator’s Brochure, consent forms, information concerning patient recruitment, 
payment or compensation procedures, or other pertinent information) will be submitted to the IRB. The 
IRB unconditional approval of the study protocol and the informed consent form will be in the possession 
of the Investigator before the study is initiated. This approval must refer to the study by exact protocol 
title and number and should identify the documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without prior written IRB 
approval except when necessary to eliminate immediate hazards to the patients or when the change(s) 
involves only logistical or administrative aspects of the study.  Such modifications will be submitted to 
the IRB and written verification that the modification was submitted and subsequently approved should 
be obtained.   


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The IRB must be informed of revisions to other documents originally submitted for review; serious and/or 
unexpected adverse experiences occurring during the study in accordance with the standard operating 
procedures and policies of the IRB; new information that may affect adversely the safety of the patients of 
the conduct of the study; an annual update and/or request for re-approval; and when the study has been 
completed. 
15.10 
Informed Consent Form  
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US Code of 
Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, 
Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, if applicable), and local 
regulations. 
The Investigator will prepare the informed consent form, and HIPAA authorization and provide the 
documents to the IRB/.  The consent form generated by the Investigator must be approved by the IRB.  
The written consent document will embody the elements of informed consent as described in the 
International Conference on Harmonisation and will also comply with local regulations. The Investigator 
will include the IRB/ -approved copy of the Informed Consent Form in the study file. 
A properly executed, written, informed consent will be obtained from each subject prior to entering the 
subject into the trial.  Information should be given in both oral and written form and subjects (or their 
legal representatives) must be given ample opportunity to inquire about details of the study.  If a subject is 
unable to sign the informed consent form (ICF) and the HIPAA authorization, a legal representative may 
sign for the subject.   A copy of the signed consent form) will be given to the subject or legal 
representative of the subject and the original will be maintained with the subject’s records. 
15.11 
Publications  
The publication or presentation of any study results shall comply with all applicable privacy laws, 
including, but not limited to, the Health Insurance Portability and Accountability Act of 1996.  
15.12 
Investigator Responsibilities 
By signing the Agreement of Investigator form, the Investigator agrees to: 
1. 
Conduct the study in accordance with the protocol and only make changes after notifying the 
Sponsor (or designee), except when to protect the safety, rights or welfare of subjects. 
2. 
Personally, conduct or supervise the study (or investigation). 
3. 
Ensure that the requirements relating to obtaining informed consent and IRB review and approval 
meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. 
Report to the Sponsor or designee any AEs that occur in the course of the study, in accordance with 
§21 CFR 312.64. 
5. 
Ensure that all associates, colleagues and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments. 
6. 
Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to make those 
records available for inspection with the Sponsor (or designee). 


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7. 
Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be responsible for 
initial and continuing review and approval of the clinical study. 
8. 
Promptly report to the IRB and the Sponsor (or designee) all changes in the research activity and all 
unanticipated problems involving risks to subjects or others (to include amendments and IND safety 
reports). 
9. 
Seek IRB approval before any changes are made in the research study, except when necessary to 
eliminate hazards to the patients/subjects. 
10. Comply with all other requirements regarding the obligations of clinical investigators and all other 
pertinent requirements listed in § 21 CFR part 312. 
 
 
 


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APPENDIX 1.  EXAMPLE OF SCHEDULE OF STUDY SCHEDULE 
 
Day 1* 
Days 3 and 7* 
if hospitalized 
Day 30 
Day 90 
Informed 
Consent 
X 
 
 
 
Medical History 
X 
 
 
X 
Height 
X 
 
 
 
Weight 
X 
 
 
 
Vital Signs 
X 
 
 
 
Troponin 
X 
X 
 
 
BNP 
X 
X 
 
 
C-Reactive 
Protein 
X 
X 
 
 
D-Dimer 
X 
X 
 
 
Echocardiogram 
X 
 
 
 
WHO 
ORDINAL 
SCORE 
X 
 
X 
X 
 
 
* All labs can be obtained within ±1 day of the assigned time, baseline echocardiogram can be obtained 
within ±3 day of the assigned time.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX 2.  EXAMPLE OF SUBJECT DIARY 
 
 
 
 
 
 


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