Lead Investigator: Charles Horsburgh, Boston University School of Public Health
Title of Proposal Research: Predictors of emergence of drug resistance while on treatment for multidrug-resistant tuberculosis: a meta-analysis
Vivli Data Request: 8846
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Tuberculosis was the leading cause of death due to an infectious disease prior to the emergence of the COVID-19 pandemic. Multidrug resistant-tuberculosis (MDR-TB) is tuberculosis that is resistant to both of the most effective first-line TB medications, isoniazid and rifampin. There were an estimated 450,000 incident cases of MDR-TB in 2021. Treatment of MDR-TB can be difficult and cumbersome because of the necessity of using less effective medications that can often cause severe adverse events or require frequent visits to TB clinics for injections of medications. If emergence of new drug resistance occurs over the course of infection, the prescribed drug regimen may be rendered less effective.
In this study, we want to identify potential predictors of emergence of drug resistance. We will measure several variables at the beginning of follow-up, when participants are prescribed the anti-MDR-TB drug regimen. We will identify participants who develop resistance to at least one MDR-TB medication while they are on treatment for MDR-TB disease. We will then compare those who do develop resistance to those who do not to identify whether there are any characteristics present at the beginning of treatment that may indicate whether someone is at risk of developing resistance. The purpose of this study is to potentially identify those who will be at higher risk for poorer treatment outcomes and may need specialized monitoring while being treated for MDR-TB. The benefit of this study will be to assist clinicians in identifying those who are at risk for emergence of drug resistance while on treatment for MDR-TB, which may potentially improve treatment outcomes for these individuals.
One difficulty of studying emergence of drug resistance as an outcome is that it occurs rarely, and many studies of people with MDR-TB tend to have few participants. We will therefore attempt to combine data from three studies together for a meta-analysis in order to maximize the number of outcomes we can identify. The three studies include one clinical trial of delamanid included in a standard of care regimen, an agent being investigated for use in treatment of MDR-TB, compared to only a standard of care regimen. The second and third studies are both cohort studies of people who are on treatment for MDR-TB. Combining these studies will allow us to observe a rare outcome with enough frequency to be able to confidently answer our question – what are potential predictors of emergence of drug resistance while on treatment for MDR-TB?
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate the Safety and Efficacy of Delamanid (OPC-67683) Administered Orally as 200 mg Total Daily Dose for Six Months in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis
Data Contributor: Otsuka Pharmaceuticals
Study ID: NCT01424670
Sponsor ID: 242-09-213