Adding Colchicine to Tocilizumab in Patients With Severe COVID-19 Pneumonia.

• Status: Recruiting
• Trial end date: 2022-08-30
• Target enrollment: 0
• Participant gender: All

Summary

Colchicine acts upstream in the cytokines cascade by inhibiting the NLRP3 inflammasome while IL-6 receptor antagonists (tocilizumab) block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm and hence the need for invasive mechanical ventilation and eventually death. Therefore, we aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia in an attempt to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia and already received tocilizumab according to local protocol. Enrolled patient will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up until discharge or for 30 days, whichever comes first. Data will be collected from electronic medical profiles. The primary efficacy outcome will be rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hamad Medical Corporation
• Treatments: Colchicine

Criteria

Inclusion Criteria:

• - Alert and conscious adults with the age of > 18 years old Severe COVID-19 pneumonia

o SpO2 <94% on room air at sea level, respiratory frequency >30 breaths/min, or lung infiltrates >50%

• Received tocilizumab within 10 days prior to enrollment

• Tocilizumab is co-admisnitered with a systemic corticosteroid

• Agree to sign conflict of interest

Exclusion Criteria:

• - Severe COVID-19 pneumonia requiring invasive mechanical ventilation

• Creatinine clearance < 30 mL/min

• End stage renal disease on hemodialysis

• ALT and/or AST > 5 upper limit of normal

• Pregnancy

• Lactation

• To prevent colchicine toxicity, patients receiving a strong CYP3A4 inhibitor (eg clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, atazanavir), a moderate CYP3A4 inhibitor (eg diltiazem, verapamil, fluconazole, amprenavir, aprepitant, fosamprenavir) or a P-gp Inhibitor (eg cyclosporine, ranolazine), will be excluded