Lessons from a randomised clinical trial for multidrug-resistant tuberculosis.

Area of Science:

• Clinical Research
• Infectious Diseases
• Pharmacology

Background:

• Multidrug-resistant tuberculosis (MDR-TB) treatment lacks robust evidence from randomized clinical trials (RCTs).
• Current MDR-TB treatment relies on expert opinion and case series.
• There is a critical need for evidence-based treatment strategies for MDR-TB.

Purpose of the Study:

• To identify and describe challenges in conducting an RCT for MDR-TB treatment.
• To evaluate the feasibility of a pilot Phase I/II RCT for MDR-TB.
• To assess the safety and tolerability of linezolid in MDR-TB patients.

Main Methods:

• A double-blind, placebo-controlled RCT (Tuberculosis Trials Consortium Study 30) was conducted.
• The study investigated 16 weeks of daily, low-dose linezolid for MDR-TB.
• Safety and tolerability were primary endpoints.

Main Results:

• Patient recruitment was significantly lower than targeted (36/64 patients, 56%).
• Low completion rates were observed, with only 69% of enrolled patients finishing at least 90 doses.
• A notable discrepancy (25%) was found between assigned treatment and actual study drug administered.

Conclusions:

• Recruitment and retention of participants in MDR-TB RCTs present substantial challenges.
• Early patient withdrawal was common, highlighting the need for early supportive interventions.
• Discrepancies in drug administration underscore the necessity for enhanced administrative controls in clinical trials.