Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial

Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial

Introduction Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15–20 mg/kg/day, is associated with serious adverse drug events (A...

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Main Authors: Andrea Benedetti, Cecilia T Costiniuk, Kosar Khwaja, Andrew Johnson, Barret Rush, Darrell Tan, Ranjani Somayaji, Salman Qureshi, Michaeline McGuinty, Nicole Ezer, Sara Belga, Emily G. McDonald, Zahra N. Sohani, Guillaume Butler-Laporte, Andrew Aw, Alex Carignan, Matthew P. Cheng, Bryan Coburn, Dan Gregson, Alexander Lawandi, Victor Leung, Sylvain Lother, Derek MacFadden, Leighanne Parkes, Valerie Roy, Ilan Schwartz, Miranda So, Emilie Trinh, Todd C. Lee
Format: Article
Language:English
Published: BMJ Publishing Group 2022-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/12/7/e053039.full
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Summary:Introduction Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15–20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%–60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality.Methods and analysis A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI.Ethics and dissemination This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal.Trial registration number NCT04851015.
ISSN:2044-6055

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