COVID-19
Conditions
Brief summary
Participants will be randomized in a 1:1 ratio to receive Colchicine plus current care per UCLA treating physicians versus current care per UCLA treating physicians alone (control arm). Importantly, this adaptive trial design allows for patients in either study arm to receive other investigational drugs for COVID-19 as new science emerges.
Interventions
COLCRYS (colchicine, USP) tablets for oral administration, containing 0.6 mg of the active ingredient colchicine USP, administered po every 12 hours x 30 days.
OTHERCurrent care per UCLA treating physicians
Current care
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Random assignment to study arms in a 1:1 ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed COVID-19 infection by polymerase chain reaction * Cardiac injury, including any of the following: * Elevated troponin level * Elevated B-type natriuretic peptide (BNP) level * New ischemic or arrhythmogenic changes on ECG/telemetry * New decrease in left ventricular ejection fraction (LVEF) or new pericardial effusion on echocardiogram * Able to provide informed consent
Exclusion criteria
* Pregnancy, breastfeeding mothers, and women of childbearing age who are unable to use 2 forms of contraception, which includes: * Intrauterine devices (IUD), contraceptive implants, or tubal sterilization * Hormone methods with a barrier method * Two barrier methods * If a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must also be used in conjunction * Co-administration of Cytochrome P450 3A4 (CYPA3A4) and P-glycoprotein (P-gp) transport system inhibitors * Concurrent use of strong CYP3A4 or P-gp inhibitors in patients with renal or hepatic impairment; * Severe hematologic or neuromuscular disorders * Severe renal impairment with concomitant hepatic impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of All-cause Mortality, Need for Mechanical Ventilation, or Need for Mechanical Circulatory Support (MCS) | 90 Days | Number of participants experiencing any of the following: All-cause mortality, need for mechanical ventilation, or need for mechanical circulatory support (MCS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | Change from baseline BNP level (Day 1) to maximum level of BNP among measures taken during hospitalization and at 30 days |
| Change in Left Ventricular Ejection Fraction (LVEF) on Echocardiography | Baseline, Day 30 | Number of participants experiencing LVEF of \< 50% on echocardiogram with failure to show an improvement of ≥ 5% at 30 days |
| Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | Change from baseline CRP level (Day 1) to maximum level of CRP among measures taken during hospitalization and at 30 days |
| Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | Change from baseline D-Dimer level (Day 1) to maximum level among measures taken during hospitalization and at 30 days. D-Dimer is a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis, so named because it contains two D fragments of the fibrin protein joined by a cross-link. |
| Delta (Peak Minus Baseline) Troponin Level | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | Change from initial troponin level to maximum level of troponin among measures taken during hospitalization and at 30 days |
| Number of Participants Requiring Mechanical Ventilation | 90 days | — |
| Number of Participants Requiring Mechanical Circulatory Support (MCS) | 90 days | — |
| Re-hospitalization at 90 Days | 90 days | Number of participants released and re-admitted to the hospital within 90 days of enrollment |
| All-cause Mortality | 90 days | — |
| Composite Event-Free Survival Over Time (Days) | Days 0, 10, 20, 30, 40, 50, 60, 70, 80, and 90 | Participants reaching primary (composite) endpoint were subtracted from event-free survival reported at 10-day intervals |
Countries
United States
Participant flow
Recruitment details
Of 304 screened individuals that met inclusion criteria,169 met exclusion criteria, 11 had co-enrollment conflicts with other clinical trials, 31 declined to participate.
Participants by arm
| Arm | Count |
|---|---|
| Colchicine Plus Current Care Colchicine 0.6 mg po BID x 30 days plus current care per UCLA treating physicians
Colchicine Tablets: COLCRYS (colchicine, USP) tablets for oral administration, containing 0.6 mg of the active ingredient colchicine USP, administered po every 12 hours x 30 days.
Current care per UCLA treating physicians: Current care | 48 |
| Current Care Alone Current care per UCLA physicians alone (control arm)
Current care per UCLA treating physicians: Current care | 45 |
| Total | 93 |
Baseline characteristics
| Characteristic | Colchicine Plus Current Care | Current Care Alone | Total |
|---|---|---|---|
| Age, Continuous | 71.2 years STANDARD_DEVIATION 17 | 71.5 years STANDARD_DEVIATION 19.5 | 71.3 years STANDARD_DEVIATION 18.2 |
| Body Mass Index (BMI) | 29.6 kg/m^2 STANDARD_DEVIATION 6.9 | 28.4 kg/m^2 STANDARD_DEVIATION 8 | 29.0 kg/m^2 STANDARD_DEVIATION 7.4 |
| Clinical Risk Factors Cerebrovascular Disease | 4 Participants | 8 Participants | 12 Participants |
| Clinical Risk Factors Chronic Kidney Disease | 18 Participants | 8 Participants | 26 Participants |
| Clinical Risk Factors COPD | 5 Participants | 5 Participants | 10 Participants |
| Clinical Risk Factors Diabetes | 19 Participants | 16 Participants | 35 Participants |
| Clinical Risk Factors Hyperlipidemia | 35 Participants | 23 Participants | 58 Participants |
| Clinical Risk Factors Hypertension | 39 Participants | 34 Participants | 73 Participants |
| Clinical Risk Factors Other Lung Disease | 5 Participants | 5 Participants | 10 Participants |
| Clinical Risk Factors Tobacco use (current or former) | 14 Participants | 19 Participants | 33 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 18 Participants | 20 Participants | 38 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 21 Participants | 49 Participants |
| Region of Enrollment United States | 48 participants | 45 participants | 93 participants |
| Sex: Female, Male Female | 9 Participants | 21 Participants | 30 Participants |
| Sex: Female, Male Male | 39 Participants | 24 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 48 | 6 / 45 |
| other Total, other adverse events | 2 / 48 | 0 / 45 |
| serious Total, serious adverse events | 0 / 48 | 0 / 45 |
Outcome results
Primary
Composite of All-cause Mortality, Need for Mechanical Ventilation, or Need for Mechanical Circulatory Support (MCS)
Number of participants experiencing any of the following: All-cause mortality, need for mechanical ventilation, or need for mechanical circulatory support (MCS)
Time frame: 90 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colchicine Plus Current Care | Composite of All-cause Mortality, Need for Mechanical Ventilation, or Need for Mechanical Circulatory Support (MCS) | 9 Participants |
| Current Care Alone | Composite of All-cause Mortality, Need for Mechanical Ventilation, or Need for Mechanical Circulatory Support (MCS) | 6 Participants |
Secondary
All-cause Mortality
Time frame: 90 days
Population: in the rare event of missing data, patients were excluded from analyses
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colchicine Plus Current Care | All-cause Mortality | 8 Participants |
| Current Care Alone | All-cause Mortality | 6 Participants |
Secondary
Change in Left Ventricular Ejection Fraction (LVEF) on Echocardiography
Number of participants experiencing LVEF of \< 50% on echocardiogram with failure to show an improvement of ≥ 5% at 30 days
Time frame: Baseline, Day 30
Population: no participant was able to receive a repeat echocardiogram at day 30
Secondary
Composite Event-Free Survival Over Time (Days)
Participants reaching primary (composite) endpoint were subtracted from event-free survival reported at 10-day intervals
Time frame: Days 0, 10, 20, 30, 40, 50, 60, 70, 80, and 90
Population: in the rare event of missing data, patients were excluded from analyses
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 20 | 36 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 50 | 35 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 10 | 40 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 60 | 34 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 30 | 35 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 70 | 34 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 0 | 48 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 80 | 34 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 40 | 35 Participants |
| Colchicine Plus Current Care | Composite Event-Free Survival Over Time (Days) | Day 90 | 34 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 90 | 33 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 0 | 41 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 10 | 40 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 20 | 38 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 30 | 37 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 40 | 36 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 50 | 36 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 60 | 36 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 70 | 36 Participants |
| Current Care Alone | Composite Event-Free Survival Over Time (Days) | Day 80 | 36 Participants |
Secondary
Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level
Change from baseline BNP level (Day 1) to maximum level of BNP among measures taken during hospitalization and at 30 days
Time frame: Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized
Population: Participants with analyzable samples at each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Colchicine Plus Current Care | Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Baseline | 503 pg/mL | Standard Deviation 765 |
| Colchicine Plus Current Care | Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Peak | 611 pg/mL | Standard Deviation 796 |
| Colchicine Plus Current Care | Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Delta | 108 pg/mL | Standard Deviation 218 |
| Current Care Alone | Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Baseline | 389 pg/mL | Standard Deviation 798 |
| Current Care Alone | Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Peak | 514 pg/mL | Standard Deviation 817 |
| Current Care Alone | Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Delta | 134 pg/mL | Standard Deviation 241 |
Secondary
Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level
Change from baseline CRP level (Day 1) to maximum level of CRP among measures taken during hospitalization and at 30 days
Time frame: Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized
Population: Participants with analyzable samples at each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Baseline | 9.9 mg/dL | Standard Deviation 7.3 |
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Peak | 13.6 mg/dL | Standard Deviation 8.9 |
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Delta | 3.9 mg/dL | Standard Deviation 7.2 |
| Current Care Alone | Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Baseline | 7.2 mg/dL | Standard Deviation 5.7 |
| Current Care Alone | Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Peak | 9.8 mg/dL | Standard Deviation 7.8 |
| Current Care Alone | Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Delta | 2.6 mg/dL | Standard Deviation 4.1 |
Secondary
Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level
Change from baseline D-Dimer level (Day 1) to maximum level among measures taken during hospitalization and at 30 days. D-Dimer is a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis, so named because it contains two D fragments of the fibrin protein joined by a cross-link.
Time frame: Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized
Population: Participants with analyzable samples at each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Baseline | 493.4 µg/mL | Standard Deviation 854 |
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Peak | 638.9 µg/mL | Standard Deviation 1112 |
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Delta | 145.5 µg/mL | Standard Deviation 353 |
| Current Care Alone | Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Baseline | 669 µg/mL | Standard Deviation 1101 |
| Current Care Alone | Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Peak | 861 µg/mL | Standard Deviation 1564 |
| Current Care Alone | Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Delta | 212 µg/mL | Standard Deviation 604 |
Secondary
Delta (Peak Minus Baseline) Troponin Level
Change from initial troponin level to maximum level of troponin among measures taken during hospitalization and at 30 days
Time frame: Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) Troponin Level | Baseline | 0.1 ng/mL | Standard Deviation 0.1 |
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) Troponin Level | Peak | 0.2 ng/mL | Standard Deviation 0.4 |
| Colchicine Plus Current Care | Delta (Peak Minus Baseline) Troponin Level | Delta | 0.1 ng/mL | Standard Deviation 0.3 |
| Current Care Alone | Delta (Peak Minus Baseline) Troponin Level | Baseline | 0.10 ng/mL | Standard Deviation 0.5 |
| Current Care Alone | Delta (Peak Minus Baseline) Troponin Level | Peak | 0.1 ng/mL | Standard Deviation 0.5 |
| Current Care Alone | Delta (Peak Minus Baseline) Troponin Level | Delta | 0 ng/mL | Standard Deviation 0 |
Secondary
Number of Participants Requiring Mechanical Circulatory Support (MCS)
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colchicine Plus Current Care | Number of Participants Requiring Mechanical Circulatory Support (MCS) | 0 Participants |
| Current Care Alone | Number of Participants Requiring Mechanical Circulatory Support (MCS) | 0 Participants |
Secondary
Number of Participants Requiring Mechanical Ventilation
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colchicine Plus Current Care | Number of Participants Requiring Mechanical Ventilation | 4 Participants |
| Current Care Alone | Number of Participants Requiring Mechanical Ventilation | 2 Participants |
Secondary
Re-hospitalization at 90 Days
Number of participants released and re-admitted to the hospital within 90 days of enrollment
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colchicine Plus Current Care | Re-hospitalization at 90 Days | 7 Participants |
| Current Care Alone | Re-hospitalization at 90 Days | 10 Participants |