Low Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Jirovecii Pneumonia

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection of immunocompromised hosts which causes in significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day of TMP, is associated with serious adverse events, including hypersensitivity reactions, drug-induced liver injury, cytopenia, and renal failure occurring among 20-60% of patients. The frequency of adverse events increases in a dose dependent manner and commonly limits the use of TMP-SMX. Reduced treatment doses of TMP-SMX for PCP reduced ADEs without mortality differences in a recent meta-analysis of observational studies. We therefore propose a Phase III randomized, placebo-controlled trial to directly compare the efficacy and safety of low dose (10 mg/kg/day of TMP) compared to the standard-of-care (15 mg/kg/day) among patients with PCP for the primary outcome of Win Ratio hierarchical composite of death, ECMO, invasive ventilation, grade 4 toxicity, non-invasive ventilation, change of therapy and length of stay.

NCT Number	NCT04851015
Lead Sponsor	Todd C. Lee MD MPH FIDSA
Conditions	Pneumocystis, Pneumocystis Pneumonia, Pneumocystis Jirovecii Infection, Pneumocystis Infections, Pneumocystis Carinii Infection, Pneumocystosis; Pneumonia (Etiology), Pneumocystis Carinii; Infection, Resulting From HIV Disease, Pneumocystosis Associated With AIDS
Enrollment	416 participants
Start Date	2025-11-28
Primary Completion	2030-09-30 (estimated)
Study Completion	2030-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-02-20