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.
18 years or older
Immunocompromised (including but not limited to HIV, solid organ transplant, solid tumors, hematological stem cell transplant and malignancies, systemic diseases, chemotherapy, long term corticosteroid use, and immunosuppressive therapies, as well as primary immunodeficiencies
Presentation to a day hospital, emergency department, or admitted to hospital
Proven or probable diagnosis of PCP using an adapted version of the 2021 EORTC/MSGERC criteria.
Previous severe adverse reaction to TMP-SMX, any sulfa drug, or any component of formulation
Compliant with PCP prophylaxis for ≥4 weeks with TMP-SMX at enrollment
More than 96 hours of any therapy for PCP
Hepatic impairment marked by alanine aminotransferase levels ≥5 times the upper limit of normal
Todd C. Lee MD MPH FIDSA
Lead sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor institution