COMBATCOVID19: COlchicine in Moderate-severe Hospitalized Patients Before ARDS to Treat COVID-19

• Sponsor: Maimonides Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04363437
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 3.2
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

The most prevalent complication of COVID-19 infection is respiratory failure from severe acute respiratory syndrome (SARS), the leading cause of mortality. There is increasing indication that the decompensation in severe COVD-19 infection may be due to a cytokine storm syndrome. This hyperinflammatory syndrome results in a fulminant and fatal hypercytokinemia and multiorgan failure.

Approximately 15% of patients with COVID-19 infection are hospitalized and 20-30% of these hospitalized patients require ICU care and/or mechanical ventilation. Overall mortality in hospitalized patients is approximately 20-25%. There is significant interest in therapies that can be given upstream to reduce the rate of mechanical ventilation and thus mortality.

We hypothesize that treatment with colchicine in COVID-19 moderate-severe patients may decrease the risk of progression into ARDS requiring increased oxygen requirements, mechanical ventilation, and mortality.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Infection	Drug: Colchicine; Drug: Usual Care	Phase 2

Detailed Description

Prospective, completely randomized, open labeled, controlled study. Patients will be randomized into two groups (A and B). Patients of group A will be treated under what is considered current standard of care at Maimonides Medical Center while group B patients will receive colchicine in addition to standard of care.

Treatment arm

In addition to the local standard of care for COVID 19 patients, the patient will receive colchicine PO as such:

• Loading dose of 1.2 mg followed by 0.6mg after 2 hours if without significant gastrointestinal symptoms (day 1)

• The next day 0.6mg bid for 14 days or until discharge

Patients who are on HMG-Co A Reductase Inhibitors (atorvastatin, fluvastatin, pravastatin, simvastatin), fibrates, genfibrozil, amiodarone, dronedarone or digoxin should have the colchicine dosage reduced to a loading dose of 0.6mg followed by 0.3mg after two hours (day

1. followed by 0.3mg BID for 14 days or until discharge.

If patients have significant gastrointestinal symptoms after loading, the dosage may be reduced to 0.3mg BID for the rest of the 14 day course or until discharge. If gastrointestinal symptoms continue, the medication should then be discontinued. Patients who experience sensory motor neuropathy, or symptoms and laboratory findings consistent with rhabdomyolysis should prompt immediate discontinuation of the drug. If renal function deteriorates during the treatment course and CrCl <30ml/min, colchicine should also be discontinued.

Control arm Usual medical therapy (can include medications such as hydroxychloroquine, azithromycin)

Patients should NOT receive, Remdesivir, IL-6 inhibitors (Tociluzimab, Sarilumab), JAK inhibitors, IL-1 inhibitors, or other immunomodulators for COVID-19 before randomization. Since the primary clinical endpoint is progression of disease, if the patient requires beyond 8L nasal cannula, eg. high flow O2 or mechanical ventilation, the primary clinical endpoint is met and the above experimental medications will be permitted. To rephrase, the patient will be allowed, Remdesivir, IL-6 inhibitors and other immunomodulators if then deemed medically necessary by the treating physician.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: COlchicine in Moderate-severe Hospitalized Patients Before ARDS to Treat COVID-19 (the COMBAT-COVID-19 Pilot Study)
• Actual Study Start Date: Apr 26, 2020
• Actual Primary Completion Date: Jul 31, 2020
• Actual Study Completion Date: Jul 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Colchine	Drug: Colchicine; People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.
Active Comparator: Usual Care	Drug: Usual Care; COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Requiring Supplemental Oxygen Beyond 8L Nasal Cannula [through study completion, estimated 2 months]

Secondary Outcome Measures

1. Percentage of Patients Who Will Require Mechanical Ventillation [through study completion, estimated 2 months]

2. Mortality [through study completion, estimated 2 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• Males and females >=18 years of age

• Willing and able to provide written informed consent prior to performing study procedures

• Currently hospitalized and requiring medical care for COVID-19

• Significant COVID-19 symptom, or judged by the treating provider to be at high risk of progression to severe COVID-19 infection

• Significant COVID-19 symptoms are defined by one or more of the following:

1. Dyspnea

2. Respiratory frequency ≥ 30/min

3. Blood oxygen saturation ≤ 93%

• AND one or more of the following: (positive PCR test or positive antibodies) or (CT/Chest X-ray consistent with COVID19 infection) or (anosmia).

Exclusion Criteria:

• Requirement of oxygen supplementation >8L nasal cannula

• Pregnancy

• Known hypersensitivity to colchicine

• Patient currently in shock or with hemodynamic instability requiring pressors

• History of cirrhosis

• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5X upper limit of normal (ULN)

• Patients with severe renal disease, CrCl <30ml/min

• Patients requiring invasive mechanical ventilation at screening or Clinical estimation that the patient will require mechanical respiratory support within 24 hours

• Patient is currently taking colchicine for other indications (gout or Familial Mediterranean Fever)

• Patient received Remdesivir, Sarilumab, Tociluzimab, Lopinavir/Ritonavir or other immunomodulator given for COVID-19 treatment (Note: Convalescent plasma infusion is not an exclusion)

• Patient is on (and cannot discontinue) a strong CYP3A4 inhibitor (eg clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, atazanavir), a moderate CYP3A4 inhbitor (eg diltiazem, verapamil, fluconazole, amprenavir, aprepitant, fosamprenavir) or a P-gp Inhibitor (eg cyclosporine, ranolazine)

• Patient is undergoing chemotherapy for cancer

• Patient is considered by the investigator, for any reason, to be unsuitable candidate for the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maimonides Medical Center	Brooklyn	New York	United States	11219

Sponsors and Collaborators

• Maimonides Medical Center

Investigators

• Principal Investigator: Felix Yang, MD, Maimonides Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 24, 2020

More Information

Publications

None provided.

• Responsible Party: Maimonides Medical Center
• ClinicalTrials.gov Identifier: NCT04363437
• Other Study ID Numbers: 2020-04-12
• First Posted: Apr 27, 2020
• Last Update Posted: Feb 18, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Maimonides Medical Center: colchicine; anti-inflammatory
• Additional relevant MeSH terms: Coronavirus Infections; Colchicine

Study Results

Participant Flow

Arm/Group Title	Colchine	Usual Care
Arm/Group Description	Colchicine: People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.	Usual Care: COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
Period Title: Overall Study
STARTED	10	11
COMPLETED	10	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Colchine	Usual Care	Total
Arm/Group Description	Colchicine: People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.	Usual Care: COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.	Total of all reporting groups
Overall Participants	10	11	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.9 (18.1)	67.1 (20.4)	64.47 (19.19)
Sex: Female, Male (Count of Participants)
Female	4 40%	5 45.5%	9 42.9%
Male	6 60%	6 54.5%	12 57.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	11 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Requiring Supplemental Oxygen Beyond 8L Nasal Cannula
Time Frame	through study completion, estimated 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchine	Usual Care
Arm/Group Description	Colchicine: People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.	Usual Care: COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
Measure Participants	10	11
Count of Participants [Participants]	1 10%	1 9.1%

2. Secondary Outcome

Title	Percentage of Patients Who Will Require Mechanical Ventillation
Time Frame	through study completion, estimated 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchine	Usual Care
Arm/Group Description	Colchicine: People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.	Usual Care: COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
Measure Participants	10	11
Count of Participants [Participants]	1 10%	0 0%

3. Secondary Outcome

Title	Mortality
Time Frame	through study completion, estimated 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Colchine	Usual Care
Arm/Group Description	Colchicine: People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.	Usual Care: COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
Measure Participants	10	11
Count of Participants [Participants]	0 0%	1 9.1%

Adverse Events

Time Frame	2 months
Arm/Group Title	Colchine		Usual Care
Arm/Group Description	Colchicine: People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1. After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.		Usual Care: COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
All Cause Mortality
	Colchine		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/11 (9.1%)
Serious Adverse Events
	Colchine		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Colchine		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.