BACKGROUND: The treatment of multidrug-resistant tuberculosis (MDR-TB) is currently based upon expert opinion and findings from case series, rather than upon randomised clinical trials (RCTs). OBJECTIVE: To describe the challenges encountered during an RCT for the treatment of MDR-TB. METHODS: Tuberculosis Trials Consortium Study 30 was a pilot, Phase I/II, double-blind, placebo-controlled, RCT of the safety and tolerability of 16 weeks of daily, low-dose linezolid treatment for MDR-TB. RESULTS:A total of 36 patients, 56% of the target of 64 patients, consented to participate, for an average of 0.69 enrolments per week. Of the 36 patients enrolled, only 25 (69%) completed at least 90 doses of study treatment. Among the 12 (33%) patients who did not complete all 112 doses of the study treatment, the median time to study withdrawal was 15 days (range 0-92). After the study, we discovered discordance between treatment assignment and study drug for at least 9 (25%) of the 36 patients. CONCLUSIONS: Recruitment and retention in this MDR-TB clinical trial posed substantial challenges, suggesting the need for a large, multidisciplinary group of study staff to support the participants. Withdrawal tended to occur early in study treatment. The discrepancy in assigned study medication reflects the need for stronger administrative controls for study drugs.
RCT Entities:
BACKGROUND: The treatment of multidrug-resistant tuberculosis (MDR-TB) is currently based upon expert opinion and findings from case series, rather than upon randomised clinical trials (RCTs). OBJECTIVE: To describe the challenges encountered during an RCT for the treatment of MDR-TB. METHODS:Tuberculosis Trials Consortium Study 30 was a pilot, Phase I/II, double-blind, placebo-controlled, RCT of the safety and tolerability of 16 weeks of daily, low-dose linezolid treatment for MDR-TB. RESULTS: A total of 36 patients, 56% of the target of 64 patients, consented to participate, for an average of 0.69 enrolments per week. Of the 36 patients enrolled, only 25 (69%) completed at least 90 doses of study treatment. Among the 12 (33%) patients who did not complete all 112 doses of the study treatment, the median time to study withdrawal was 15 days (range 0-92). After the study, we discovered discordance between treatment assignment and study drug for at least 9 (25%) of the 36 patients. CONCLUSIONS: Recruitment and retention in this MDR-TB clinical trial posed substantial challenges, suggesting the need for a large, multidisciplinary group of study staff to support the participants. Withdrawal tended to occur early in study treatment. The discrepancy in assigned study medication reflects the need for stronger administrative controls for study drugs.
Authors: Thelma Tupasi; Rajesh Gupta; Manfred Danilovits; Andra Cirule; Epifanio Sanchez-Garavito; Heping Xiao; Jose L Cabrera-Rivero; Dante E Vargas-Vasquez; Mengqiu Gao; Mohamed Awad; Leesa M Gentry; Lawrence J Geiter; Charles D Wells Journal: Bull World Health Organ Date: 2015-11-17 Impact factor: 9.408