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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2022-07-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Andrea Benedetti |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-93d2ad50457b4909a009a29a7dcc8958 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-07-01 |
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| spelling | doaj-art-93d2ad50457b4909a009a29a7dcc89582025-01-30T15:05:13ZengBMJ Publishing GroupBMJ Open2044-60552022-07-0112710.1136/bmjopen-2021-053039Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trialAndrea Benedetti0Cecilia T Costiniuk1Kosar Khwaja2Andrew Johnson3Barret Rush4Darrell Tan5Ranjani Somayaji6Salman Qureshi7Michaeline McGuinty8Nicole Ezer9Sara Belga10Emily G. McDonald11Zahra N. Sohani12Guillaume Butler-Laporte13Andrew Aw14Alex Carignan15Matthew P. Cheng16Bryan Coburn17Dan Gregson18Alexander Lawandi19Victor Leung20Sylvain Lother21Derek MacFadden22Leighanne Parkes23Valerie Roy24Ilan Schwartz25Miranda So26Emilie Trinh27Todd C. Lee28Research Institute of the McGill University Health Centre, Montreal, Québec, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaDepartment of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montreal, Quebec, CanadaDepartment of Education, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaDepartment of Critical Care Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaDivision of Infectious Diseases, St Michael`s Hospital, Toronto, Ontario, CanadaDivision of Infectious Diseases, Department of Medicine, University of Calgary, Calgary, Alberta, CanadaDepartment of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montreal, Quebec, CanadaDivision of Infectious Diseases, Department of Medicine, Ottawa Hospital, Ottawa, Ontario, CanadaDivision of Respirology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaDivision of Infectious Diseases, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, CanadaMedicine, McGill University, Montreal, Quebec, CanadaDepartment of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaDivision of Hematology, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaDivision of Microbiology and Infectious Diseases, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quebec, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaDivision of Infectious Diseases, Department of Medicine, University Health Network, Toronto, Ontario, CanadaDepartments of Pathology and Laboratory Medicine and Medicine, University of Calgary, Calgary, Alberta, Canada4 Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Quebec, CanadaDepartment of Laboratory Medicine & Pathology, The University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Critical Care Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaDivision of Infectious Diseases, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, CanadaDivision of Medical Microbiology and Infectious Diseases, Lady Davis Institute for Medical Research, Montreal, Quebec, CanadaDivision of Microbiology and Infectious Diseases, Centre Hospitalier Universitaire de Sherbrooke Hôtel-Dieu, Sherbrooke, Quebec, CanadaDivision of Infectious Diseases, University of Alberta, Edmonton, Alberta, CanadaSinai Health System-University Health Network Antimicrobial Stewardship Program, University Health Network, Toronto, Ontario, CanadaResearch Institute of the McGill University Health Centre, Montreal, Quebec, CanadaDivision of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaIntroduction 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.https://bmjopen.bmj.com/content/12/7/e053039.full |
| spellingShingle | 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 Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial BMJ Open |
| title | Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial |
| title_full | Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial |
| title_fullStr | Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial |
| title_full_unstemmed | Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial |
| title_short | Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial |
| title_sort | low dose trimethoprim sulfamethoxazole for the treatment of pneumocystis jirovecii pneumonia low tmp protocol for a phase iii randomised placebo controlled dose comparison trial |
| url | https://bmjopen.bmj.com/content/12/7/e053039.full |
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