RECRUITINGPhase 3INTERVENTIONAL

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

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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. Who Should NOT Join This Trial: - 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 - Known G6PD deficiency - Known diagnosis of porphyria - Known pregnancy or breastfeeding (as per Health Canada) - Unable to provide willing to sign a consent form and no available healthcare proxy (with ethics approval for deferred consent in cases of critical illness); refusal of consent; no reliable means of outpatient contact (telephone/email/text); - Previously enrolled Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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. Exclusion 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 * Known G6PD deficiency * Known diagnosis of porphyria * Known pregnancy or breastfeeding (as per Health Canada) * Unable to provide informed consent and no available healthcare proxy (with ethics approval for deferred consent in cases of critical illness); refusal of consent; no reliable means of outpatient contact (telephone/email/text); * Previously enrolled

Treatments Being Tested

DRUG

trimethoprim-sulfamethoxazole

10mg/kg/day of TMP component

DRUG

trimethoprim-sulfamethoxazole

15mg/kg/day of TMP component

Locations (1)

McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital)

Montreal, Quebec, Canada