Covid19
Conditions
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)
Interventions
DRUGColchicine
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
Sponsors
University of California, Los Angeles
Baptist Health South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Men and Women ≥ 18 years of age * Covid-19 Positive * Hospitalized patients able to provide informed consent * Cardiac injury (as evidenced by any of the following) 1. Elevated troponin level 2. Elevated BNP level 3. New ischemic or arrhythmogenic ECG/telemetry changes 4. New decrease in Left Ventricular Ejection Fraction (LVEF) or new pericardial effusion on echocardiogram
Exclusion criteria
* Pregnancy, breastfeeding mothers, and women of childbearing age who are unable to use adequate contraception, which includes: 1. Intrauterine devices (IUD), contraceptive implants, or tubal sterilization 2. Hormone method with a barrier method 3. Two barrier methods 4. If a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must also be used in conjunction * History of severe hematologic or neuromuscular disorder * Co-administration of Cytochrome P450 3A4 (CYPA3A4) and P-glycoprotein transport inhibitor * Severe renal impairment with concomitant hepatic impairment * Concurrent use of colchicine and strong or P-glycoprotein inhibitor with renal or hepatic impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 90 days | Composite of all-cause mortality |
| Mechanical Ventilation | 90 days | Need for mechanical ventilation |
| Mechanical Circulatory Support | 90 days | Need for mechanical circulatory support |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Biomarkers | baseline and 90 days | Baseline and delta (change from baseline) of C-Reactive Protein |
| Hospital Length of Stay | 90 days | Duration of Hospitalization on each arm |
| Time (Days) to the Primary End Point | 90 days | Number of days from start of therapy to either mortality or need for Mechanical Ventilation or Mechanical Circulatory Support |
| Change in Inflammatory Biomarkers | baseline and 90 days | Baseline and delta (change from baseline) of D-Dimer |
| Need for Re-hospitalization | 90 days | 90-day re-hospitalization rate |
| Peak and Delta (Change From Baseline) Troponin Level | baseline and 90 days | Change from baseline to the time when Troponin levels peak during the hospitalization |
| Baseline Brain Natriuretic Peptide (BNP) Level | baseline | Documenting baseline Brain Natriuretic Peptide (BNP) at the time of hospitalization |
Countries
United States
Participant flow
Recruitment details
The rapid decline in COVID patients and other competing trials did not allowed enrollment of additional subjects. Given the small sample size, the study was terminated.
Pre-assignment details
Patients who test positive for COVID-19, sign informed consent and have any of the study specific manifestations of cardiac injury were randomized 1:1 .
Participants by arm
| Arm | Count |
|---|---|
| Active Hospitalized covid-19 patients treated with colchicine plus current care per institution treating physicians.
Colchicine: 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 | 1 |
| Control Hospitalized covid-19 patients treated with current standard of care (per institution treating physicians) alone. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Total | Control | Active |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 2 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 | 1 / 1 |
Outcome results
Primary
Mechanical Circulatory Support
Need for mechanical circulatory support
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Mechanical Circulatory Support | 0 Participants |
| Control | Mechanical Circulatory Support | 0 Participants |
Primary
Mechanical Ventilation
Need for mechanical ventilation
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Mechanical Ventilation | 0 Participants |
| Control | Mechanical Ventilation | 0 Participants |
Primary
Mortality
Composite of all-cause mortality
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Mortality | 0 Participants |
| Control | Mortality | 0 Participants |
Secondary
Baseline Brain Natriuretic Peptide (BNP) Level
Documenting baseline Brain Natriuretic Peptide (BNP) at the time of hospitalization
Time frame: baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Baseline Brain Natriuretic Peptide (BNP) Level | 27 pg/ml |
| Control | Baseline Brain Natriuretic Peptide (BNP) Level | 205 pg/ml |
Secondary
Change in Inflammatory Biomarkers
Baseline and delta (change from baseline) of D-Dimer
Time frame: baseline and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active | Change in Inflammatory Biomarkers | Baseline | 0.46 mcg/ml |
| Active | Change in Inflammatory Biomarkers | Delta | 19 mcg/ml |
| Control | Change in Inflammatory Biomarkers | Baseline | 0.27 mcg/ml |
| Control | Change in Inflammatory Biomarkers | Delta | 0 mcg/ml |
Secondary
Hospital Length of Stay
Duration of Hospitalization on each arm
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Hospital Length of Stay | 5 days |
| Control | Hospital Length of Stay | 14 days |
Secondary
Inflammatory Biomarkers
Baseline and delta (change from baseline) of C-Reactive Protein
Time frame: baseline and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active | Inflammatory Biomarkers | Baseline | 34.2 mg/l |
| Active | Inflammatory Biomarkers | Delta | 19.1 mg/l |
| Control | Inflammatory Biomarkers | Baseline | 3.0 mg/l |
| Control | Inflammatory Biomarkers | Delta | -0.1 mg/l |
Secondary
Need for Re-hospitalization
90-day re-hospitalization rate
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Need for Re-hospitalization | 1 times hospitalized |
| Control | Need for Re-hospitalization | 2 times hospitalized |
Secondary
Peak and Delta (Change From Baseline) Troponin Level
Change from baseline to the time when Troponin levels peak during the hospitalization
Time frame: baseline and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active | Peak and Delta (Change From Baseline) Troponin Level | Delta | -0.07 ng/ml |
| Active | Peak and Delta (Change From Baseline) Troponin Level | Baseline (Peak) | 0.16 ng/ml |
| Control | Peak and Delta (Change From Baseline) Troponin Level | Delta | 0 ng/ml |
| Control | Peak and Delta (Change From Baseline) Troponin Level | Baseline (Peak) | 0.02 ng/ml |
Secondary
Time (Days) to the Primary End Point
Number of days from start of therapy to either mortality or need for Mechanical Ventilation or Mechanical Circulatory Support
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Time (Days) to the Primary End Point | 0 days |
| Control | Time (Days) to the Primary End Point | 0 days |