Low-Dose Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia
(LOW-TMP Trial)

Recruiting in Palo Alto (17 mi)

Todd C. Lee, MD, MPH, FIDSA - Research ...

Overseen ByEmily G McDonald, MD MSc

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?Pneumocystis jirovecii pneumonia (PJP) 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 PJP 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 PJP for the primary outcome of death, new mechanical ventilation, and change of treatment.

Eligibility Criteria

This trial is for immunocompromised individuals, including those with HIV, organ transplants, cancers, or on long-term steroids. They must have a proven or probable PJP diagnosis and can be in the hospital or just visiting. People who've had bad reactions to TMP-SMX/sulfa drugs, certain liver issues, started other PJP treatments over 72 hours ago, pregnant/breastfeeding women, or unable to consent are excluded.

Inclusion Criteria

I have recently visited a hospital for my condition.

I have a weakened immune system due to a condition or treatment.

Exclusion Criteria

I have been diagnosed with porphyria.

I have been diagnosed with G6PD deficiency.

My liver enzyme levels are very high.

I have been taking medication to prevent a specific lung infection for at least 4 weeks.

Participant Groups

The study tests if a lower dose of Trimethoprim-Sulfamethoxazole (10 mg/kg/day) is as effective and safer than the standard dose (15 mg/kg/day) for treating Pneumocystis jirovecii pneumonia. It's a Phase III trial where patients are randomly assigned to receive either the low dose or standard treatment.

2Treatment groups

Experimental Treatment

Active Control

Group I: Reduced dose TMP-SMXExperimental Treatment1 Intervention

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.

Group II: Standard dose TMP-SMXActive Control1 Intervention

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.