Study of Different Doses of Atorvastatin Combined with Standard Tuberculosis Treatment in Adults with Pulmonary Tuberculosis

What this Trial Is About

Researchers are studying how atorvastatin, a drug commonly used to lower cholesterol, behaves in the body when combined with the standard first-line treatment for drug-sensitive pulmonary tuberculosis TB in adults. The goal is to understand the drugs pharmacokineticsthe way it is absorbed, distributed, metabolized, and eliminatedand to develop a model that helps find the best dose of atorvastatin to use alongside TB treatment. This study is a phase 2, randomized trial conducted as a sub-study of the larger ATORTUB trial. Participants will be randomly assigned to one of four groups. Three groups will receive standard anti-TB therapy for 24 weeks combined with daily oral atorvastatin at doses of 20 mg, 40 mg, or 60 mg for the first 16 weeks. The fourth group will receive only the standard anti-TB therapy without atorvastatin. The standard TB treatment includes 8 weeks of rifampicin, isoniazid, pyrazinamide, and ethambutol followed by 16 weeks of rifampicin and isoniazid. This parallel dose comparison aims to identify the optimal atorvastatin dose for future TB treatment studies. Participants will attend several study visits over a total of 52 weeks, including 24 weeks of treatment followed by 6 months of follow-up. At each visit, sputum samples, chest X-rays, lung function tests, and blood samples for pharmacokinetic analyses will be collected. Researchers will measure key drug levels such as area under the curve AUC, peak plasma concentration, and plasma clearance for atorvastatin and TB drugs. The study will also evaluate how these drug levels relate to early bactericidal activity, sputum culture conversion, chest X-ray improvement, and lung function changes. Safety and optimal dosing will be assessed throughout the trial.

ATORvastatin in Pulmonary TUBerculosis: a POPulation PharmacoKinetics -PharmacoDynamics Sub-study (ATORTUB popPK-PD)