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

COlchicine in Moderate-severe Hospitalized Patients Before ARDS to Treat COVID-19 (the COMBAT-COVID-19 Pilot Study)

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.

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection
• Intervention / Treatment: Drug: Colchicine; Drug: Usual Care

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care	Drug: Usual Care; COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2020
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 16, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: anti-inflammatory; colchicine
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 2020-04-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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