Drug combination does not demonstrate full noninferiority, but has potential advantages
TUESDAY, April 12 (HealthDay News) -- Compared with separately administered drugs, a four-drug fixed-dose combination (FDC) regimen partially satisfies noninferiority criteria for tuberculosis treatment, according to a study published April 13 in an infectious disease and immunology themed issue of the Journal of the American Medical Association.
Christian Lienhardt, M.D., Ph.D., from the International Union Against Tuberculosis and Lung Disease in Paris, and colleagues compared the efficacy and safety of a four-drug FDC course of therapy against separate drugs in a noninferiority trial. The FDC cohort (798 patients) received daily treatment with four drugs (rifampicin, isoniazid, pyrazinamide, ethambutol), while the other group (787 patients) received the drugs separately during the eight-week intensive phase of treatment. The noninferiority margin was set at 4 percent.
The investigators found that 93.9 percent of patients in the FDC cohort had a favorable outcome, as did 94.6 percent in the separate-drugs group in a per-protocol analysis. According to two models of intention-to-treat analysis, the proportion of favorable outcomes in the FDC group and the separate group was 83.8 versus 84.8 percent and 89.8 versus 91.0 percent, respectively. There was a similar distribution of adverse events associated with trial drugs among treatment groups.
"Although the results of this study do not demonstrate full noninferiority of the FDCs with single drugs using the strict definition applied in this trial, the results do support the WHO recommendations for use of FDCs because of the potential advantages associated with their administration compared with separate-drug formulations," the authors write.