Low Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Jirovecii Pneumonia (NCT04851015) | Clinical Trial Compass
RecruitingPhase 3
Low Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Jirovecii Pneumonia
Canada416 participantsStarted 2025-11-28
Plain-language summary
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 can participate
Age range
18 Years – 100 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
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
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is testing a lower dose of trimethoprim-sulfamethoxazole — the drug many doctors already use for PCP — so could you explain what risks or side effects might be different at a lower dose compared to the standard dose I might otherwise receive?
2Since this is a Phase 3 trial, what do we already know about how this lower-dose approach has performed in earlier studies, and does that evidence change how you feel about it as an option for my situation?
3The trial is measuring something called a 'hierarchical composite outcome' — can you explain in plain terms what they're actually tracking to decide if the lower dose works, and whether those endpoints match what matters most to me, like survival or avoiding serious side effects?
4Given that I may already need to start PCP treatment urgently, is there enough time to realistically consider joining this trial, or would starting standard treatment right away make more sense for my case?
5If I enrolled and was assigned to the lower-dose arm and it wasn't working well for me, what would happen — would I be switched to standard dosing, and how quickly could that happen?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.