Recruiting
Phase 3

Trimethoprim-Sulfamethoxazole

Sponsor:

Todd C. Lee MD MPH FIDSA

Code:

NCT04851015

Conditions

Pneumocystis

Pneumocystis Pneumonia

Pneumocystis Jirovecii Infection

Pneumocystis Infections

Pneumocystis Carinii Infection

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

trimethoprim-sulfamethoxazole

trimethoprim-sulfamethoxazole

Study Details

Brief 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.

Conditions

Pneumocystis

Pneumocystis Pneumonia

Pneumocystis Jirovecii Infection

Pneumocystis Infections

Pneumocystis Carinii Infection

Study ID

NCT04851015

Start date

Nov 28, 2025

Status verified date

Feb, 2026

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Sep 30, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

416 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Reduced dose TMP-SMX

Trimethoprim-Sulfamethoxazole at a total dose of 10mg/kg/day. Oral or intravenous drug will be administered at discretion of treating team. This will be given as a dose of 10mg/kg/day open label with additional placebo tablets or intravenous placebo solution given to simulate 15mg/kg/day. All doses will be adjusted for obesity and renal function.

active comparator: Standard dose TMP-SMX

Trimethoprim-Sulfamethoxazole at a total dose of 15mg/kg/day. Oral or intravenous drug will be administered at discretion of treating team. This will be given as 10mg/kg/day open label plus an extra masked 5mg/kg/day of tablets or intravenous solution. All doses will be adjusted for obesity and renal function.

Interventions

trimethoprim-sulfamethoxazole

10mg/kg/day of TMP component

trimethoprim-sulfamethoxazole

15mg/kg/day of TMP component

Primary outcome measure

  • Hierarchical composite outcome [ Time Frame: Day 30 ]

Central Contacts and Locations

Central contacts

Babykumari Chitramuthu, PhD

514-934-1934babykumari.chitramuthu@muhc.mcgill.ca

Locations

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

Recruiting

Montreal, Quebec, Canada, H4A3J1

Contacts

Babykumari Chitramuthu, PhD

514-934-1934babykumari.chitramuthu@muhc.mcgill.ca

Kristen Moran

514-934-1934kristen.moran@mail.mcgill.ca

Principal Investigator:

Emily G McDonald, MD MSc

More Information

Sponsor

Todd C. Lee MD MPH FIDSA

Last update posted

Feb 20, 2026

Last verified

Feb, 2026

Keywords

  • Pneumocystis
  • PCP
  • PJP
  • immunosuppressed
  • HIV
  • TMP-SMX

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-12. This information was provided to ClinicalTrials.gov by Todd C. Lee MD MPH FIDSA on 2026-02-20. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.