Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a phase IIA open-label pilot clinical trial

Drug-resistant tuberculosis remains a major global health challenge, and excessive inflammation may contribute to tissue damage and poor outcomes. We conducted a phase IIA prospective open-label pilot trial (ClinicalTrials.gov: NCT02781909) evaluating adjunctive ibuprofen in adults with pulmonary pre-extensively drug-resistant (pre-XDR) or extensively drug-resistant (XDR) tuberculosis in Georgia. Twenty-eight participants received individualized background anti-tuberculosis regimens alone (n = 14) or with ibuprofen 400 mg daily for 2 months (n = 14) and were followed for 6 months. The primary efficacy outcome was the proportion of participants showing clinical and/or microbiological benefit, assessed by sputum culture conversion, radiological evolution, and WHO-defined treatment outcomes. Secondary outcomes were safety and tolerability, health-related quality of life, and inflammatory and transcriptomic responses. Adding adjunctive ibuprofen did not improve month-2 sputum culture negativity, time to stable culture conversion, radiological evolution, or final treatment outcomes. Safety and tolerability were similar between groups. Adverse events were recorded and reviewed, but not formally graded for severity. Ibuprofen treatment was associated with numerically greater reductions in several blood-based inflammatory measures and in transcriptomic signature scores associated with poor tuberculosis outcomes. These findings are exploratory and do not demonstrate clinical benefit but indicate biological activity and support evaluation of anti-inflammatory host-directed therapies in larger controlled trials.