Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial.

Summary

In a multicenter non-inferiority RCT (n=322), a 16‑week clofazimine-based regimen for drug-susceptible pulmonary TB achieved relapse, sputum conversion, and bacteriologic cure rates comparable to the standard 24‑week regimen. Safety was acceptable, supporting the feasibility of shortening first-line TB therapy pending confirmatory implementation studies.

Key Findings

• A 16-week clofazimine-based regimen was non-inferior to a 24-week standard regimen for relapse at 3 months post-treatment (3.2% vs 1.9%, within non-inferiority margin).
• Relapse at 1 year did not differ significantly between groups (RR 1.31; 95% CI 0.58–2.95).
• Sputum smear negativity and bacteriological cure at end of treatment were similar across arms, with an acceptable safety profile.

Clinical Implications

If adopted, a 4‑month clofazimine-containing regimen could become a new standard for drug-susceptible pulmonary TB, particularly in settings where adherence to 6‑month therapy is challenging; programs will need to monitor safety and resistance.

Limitations

• Open-label design and follow-up limited to 1 year for relapse outcomes.
• Generalizability beyond participating regions and in special populations (e.g., PLHIV, extrapulmonary TB) remains to be established.

Future Directions

Confirmatory pragmatic trials, pharmacovigilance for clofazimine-related adverse effects, resistance surveillance, and cost-effectiveness analyses across diverse settings are warranted.