Lead Investigator: Leo Buckley, Brigham and Women’s Hospital
Title of Proposal Research: Colchicine Adverse Effects Research in people with Covid-19 randomized to colchicine treatment
Vivli Data Request: 8700
Funding Source: NHLBI K23HL150311
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Colchicine is an established anti-inflammatory therapy used to treat hereditary auto-inflammatory conditions and pericarditis. Colchicine also can reduce the risk of certain types of heart disease. Unfortunately, colchicine can cause nausea, vomiting, diarrhea and stomach cramping. These side effects, and others, limit the use of colchicine. Certain characteristics and drug-drug interactions may identify people with high risk of colchicine side effects. Identifying those “risk factors” may help clinicians minimize colchicine’s side effects.
The overall goal of this project is to better understand how colchicine’s side effects impact its beneficial anti-inflammatory effects. Colchicine is known to cause stomach-related issues, such as nausea and vomiting, but the factors that predict and modify these side effects are unknown. The results of this project may help clinicians who prescribe colchicine for cardiovascular and other conditions.
Statistical Analysis Plan
Specific Aim 1: To test the hypothesis that older age, lower eGFR, higher AST, higher ALT and higher alkaline phosphatase associate with a higher risk of gastrointestinal and other side effects and a lower risk of death or Covid-19 hospitalization in people with Covid-19 randomized to colchicine treatment. We will build logistic regression models to estimate the associations between clinical factors and the risk of adverse effects and efficacy outcomes among participants randomized to colchicine treatment.
2) To test the hypothesis that concomitant drug-drug interactions increase the risk of gastrointestinal and other side effects and decrease the risk of death or Covid-19 hospitalization in people with Covid-19 randomized to colchicine treatment. We will build logistic regression models to estimate the associations between the presence of a colchicine drug-drug interaction and the risk of adverse effects and efficacy outcomes among participants randomized to colchicine treatment.
3) To test the hypothesis that the effects of colchicine vs. placebo on gastrointestinal and other side effects and the composite of death or Covid-19 hospitalization are modified by age, eGFR, liver enzyme levels and the presence of at least one drug-drug interaction in people with Covid-19. We will use logistic regression models to assess effect modification of the effect of colchicine vs. placebo on adverse events and efficacy outcomes according to clinical risk factors and the presence of colchicine drug-drug interactions. In addition to terms for each clinical risk factor and the presence of a drug-drug interaction, the model will include a term for treatment allocation and the interactions between treatment allocation and each risk factor or the presence of a drug-drug interaction.
Requested Studies:
Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
Data Contributor: Montreal Heart Institute
Study ID: NCT04322682
Sponsor ID: MHIPS-2020-001
Public Disclosures:
- Alfehaid L, Alkhezi O, Buckley L, Libby P, Desai A, Tawifk Y, Shah A. COLCHICINE, DRUG-DRUG INTERACTIONS AND GASTROINTESTINAL ADVERSE EFFECTS. American College of Clinical Pharmacy. Session IV. 2023.
- Alfehaid, L.S., Farah, S., Omer, A., Weber, B.N., Alkhezi, O., Tawfik, Y.M., Shah, A.M., Libby, P. and Buckley, L.F., 2024. Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19: A Secondary Analysis of the COLCORONA Randomized Clinical Trial. JAMA Network Open, 7(9), pp.e2431309-e2431309. Doi : 10.1001/jamanetworkopen.2024.31309