Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis (PCP) pneumonia
Low Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Jirovecii Pneumonia
This trial will test whether a lower daily dose of TMP‑SMX works as well but causes fewer side effects than the standard dose in adults with Pneumocystis (PCP) pneumonia who are immunocompromised.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 416 (estimated) |
| Ages | 18 Years to 100 Years |
| Sex | All |
| Sponsor | McGill University Health Centre/Research Institute of the McGill University Health Centre Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Montreal, Quebec) |
| Trial ID | NCT04851015 on ClinicalTrials.gov |
What this trial studies
This Phase III randomized, double-blind, controlled trial compares low-dose TMP‑SMX (10 mg/kg/day of trimethoprim) to standard-dose TMP‑SMX (15 mg/kg/day) for treatment of proven or probable PCP in immunocompromised adults. Participants are randomized early in therapy (within 96 hours of treatment initiation) and are enrolled at the McGill University Health Centre. The primary outcome is a Win Ratio hierarchical composite that includes death, extracorporeal membrane oxygenation (ECMO), and invasive ventilation, with secondary endpoints addressing adverse drug events and treatment tolerability. The trial is designed to test noninferiority in clinical outcomes while measuring differences in toxicity rates.
Who should consider this trial
Good fit: Adults (≥18) who are immunocompromised with a proven or probable diagnosis of PCP, presenting to hospital within 96 hours of starting therapy, and able to give informed consent without contraindications to TMP‑SMX are ideal candidates.
Not a fit: People with prior severe sulfa allergy, known G6PD deficiency, pregnancy or breastfeeding, marked hepatic impairment, or those already on full TMP‑SMX prophylaxis are unlikely to benefit from enrollment.
Why it matters
Potential benefit: If successful, the lower dose could provide the same survival and respiratory outcomes with substantially fewer serious adverse effects, making PCP treatment safer and more tolerable.
How similar studies have performed: Observational studies and a recent meta-analysis reported fewer adverse events with reduced TMP‑SMX doses without higher mortality, but randomized Phase III evidence is still needed.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Montreal, Quebec
- McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital) — Montreal, Quebec, Canada (Recruiting)
Study contacts
- Principal investigator: Emily G McDonald, MD MSc — Research Institute of the McGill University Health Centre
- Study coordinator: Babykumari Chitramuthu, PhD
- Email: babykumari.chitramuthu@muhc.mcgill.ca
- Phone: 514-934-1934
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.