Low-Dose Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia

(LOW-TMP Trial)

Overseen By Kristen Moran

Age: 18+

Sex: Any

Trial Phase: Phase 3

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

Must not be taking: Sulfa drugs

Disqualifiers: Hepatic impairment, G6PD deficiency, pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a lower dose of trimethoprim-sulfamethoxazole (TMP-SMX) is as effective as the standard dose in treating Pneumocystis jirovecii pneumonia (PJP), a lung infection affecting individuals with weakened immune systems. The trial aims to determine if the lower dose reduces the risk of serious side effects, such as kidney problems and allergic reactions, which are common with the standard dose. Individuals with a weak immune system currently being treated for PJP may be suitable candidates if they have not experienced severe reactions to TMP-SMX before. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially safer treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a lower dose of the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) causes fewer side effects than the usual dose. In one study, patients on the lower dose experienced fewer negative reactions without an increase in death rates. Another study found that the low dose is safe and results in fewer people having to stop treatment due to side effects. These studies suggest that a lower dose might be easier on the body and safer, especially for people with weakened immune systems or other health problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about low-dose Trimethoprim-Sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia because it offers a potentially safer option with fewer side effects. Unlike the standard 15mg/kg/day dose, this reduced dose of 10mg/kg/day may be just as effective while being easier on the patient's body, particularly for those with obesity or kidney issues. This new approach could maintain efficacy while minimizing the risks associated with higher dosages, making it a promising alternative for patients and healthcare providers alike.

What evidence suggests that low-dose trimethoprim-sulfamethoxazole could be an effective treatment for Pneumocystis pneumonia?

This trial will compare a reduced dose of the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) with the standard dose for treating Pneumocystis jirovecii pneumonia (PJP). Research has shown that a lower dose can effectively treat PJP. A recent study review found no difference in death rates between people taking the lower dose and those on the standard dose, suggesting the lower dose can work just as well while reducing side effects. Another study confirmed that the low-dose treatment is safe and effective for patients without HIV. Overall, using a lower dose could lead to fewer serious side effects without losing its ability to fight the infection. ^{1 2 5 6 7}

Who Is on the Research Team?

Todd C Lee, MD MPH

Principal Investigator

Research Institute of the McGill University Health Centre

Emily G McDonald, MD MSc

Principal Investigator

Research Institute of the McGill University Health Centre

Zahra N Sohani, MD PhD

Principal Investigator

Research Institute of the McGill University Health Centre

Are You a Good Fit for This Trial?

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.

You have been diagnosed with a lung infection called PJP using specific medical criteria.

Exclusion Criteria

You had a bad reaction to TMP-SMX or any sulfa drugs before.

I have been diagnosed with porphyria.

I have received treatment for PJP for more than 72 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either reduced-dose (10 mg/kg/day) or standard-dose (15 mg/kg/day) TMP-SMX for the treatment of Pneumocystis jirovecii pneumonia

21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and quality of life

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Trimethoprim-Sulfamethoxazole

Trial Overview 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.

How Is the Trial Designed?

Group I: Reduced dose TMP-SMX Experimental Treatment 1 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-SMX Active Control 1 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.

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

476

Recruited

170,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7200085/

Low-Dose TMP-SMX in the Treatment of Pneumocystis ... When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, –9% in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1341321X24002782

Efficacy and safety of a low-dose sulfamethoxazole ... This retrospective study aimed to investigate the efficacy and safety of low-dose and standard-dose regimens of ST in non-HIV patients using a large-scale ...

3. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1422490/full

Low-dose trimethoprim-sulfamethoxazole treatment for ... The recommended standard treatment for pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15-20 mg/kg/d TMP).

4. academic.oup.com academic.oup.com/ofid/article/11/9/ofae499/7747370

Intermittent Versus Daily Trimethoprim/Sulfamethoxazole ... This systematic review and meta-analysis suggests that intermittent TMP/SMX regimens for PCP prophylaxis may be more tolerable than daily ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39368745/

Outcomes of low-dose trimethoprim-sulfamethoxazole ... Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP).

6. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1545436/full

Low-dose trimethoprim-sulfamethoxazole for prophylaxis of ... Conclusion: Our findings suggested that a low-dose TMP-SMX regimen is safe and significantly reduces the discontinuation rate and total AEs compared to the ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39389264/

Efficacy and safety of a low-dose sulfamethoxazole ... This study aimed to investigate the efficacy and safety of low-dose and standard-dose regimens of ST in preventing PCP in patients with non human ...