Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial
Introduction Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood con...
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BMJ Publishing Group
2022-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/6/e061953.full |
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| author | Mark Conaway David R Boulware Scott K Heysell Stellah G Mpagama Christopher C Moore Alphonce Liyoyo Conrad Muzoora Catherine Gitige Bibie Said Edwin Nuwagira Rinah Arinaitwe Rhina Mushagara Peter Buzaare Anna Chongolo Samuel Jjunju Precious Twesigye Megan Null Tania A Thomas |
| author_facet | Mark Conaway David R Boulware Scott K Heysell Stellah G Mpagama Christopher C Moore Alphonce Liyoyo Conrad Muzoora Catherine Gitige Bibie Said Edwin Nuwagira Rinah Arinaitwe Rhina Mushagara Peter Buzaare Anna Chongolo Samuel Jjunju Precious Twesigye Megan Null Tania A Thomas |
| author_sort | Mark Conaway |
| collection | DOAJ |
| description | Introduction Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.Methods and analysis This is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.Ethics and dissemination This clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.Trial registration number ClinicalTrials.gov (NCT04618198). |
| format | Article |
| id | doaj-art-156994e3526b4bb195e15dc5549a8bf5 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-156994e3526b4bb195e15dc5549a8bf52025-01-24T18:05:12ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2022-061953Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trialMark Conaway0David R Boulware1Scott K Heysell2Stellah G Mpagama3Christopher C Moore4Alphonce Liyoyo5Conrad Muzoora6Catherine Gitige7Bibie Said8Edwin Nuwagira9Rinah Arinaitwe10Rhina Mushagara11Peter Buzaare12Anna Chongolo13Samuel Jjunju14Precious Twesigye15Megan Null16Tania A Thomas17Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USADivision of Infectious Diseases & International Medicine, University of Minnesota Twin Cities, Minneapolis, Minnesota, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USAMedical Department, Kibong’oto Infectious Diseases Hospital/Kilimanjaro Christian Medical University, Kilimanjaro, United Republic of TanzaniaDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USADepartment of Medicine, Kibong’oto Infectious Diseases Hospital, Sanya Juu, United Republic of TanzaniaDepartment of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda4 Medical, Kibong`oto Infectious Diseases Hospital, Kilimanjaro, United Republic of TanzaniaDepartment of Medicine, Kibong’oto Infectious Diseases Hospital, Sanya Juu, United Republic of TanzaniaFaculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaFaculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaFaculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaFaculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaDepartment of Medicine, Kibong’oto Infectious Diseases Hospital, Sanya Juu, United Republic of TanzaniaFaculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaFaculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USADivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USAIntroduction Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.Methods and analysis This is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.Ethics and dissemination This clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.Trial registration number ClinicalTrials.gov (NCT04618198).https://bmjopen.bmj.com/content/12/6/e061953.full |
| spellingShingle | Mark Conaway David R Boulware Scott K Heysell Stellah G Mpagama Christopher C Moore Alphonce Liyoyo Conrad Muzoora Catherine Gitige Bibie Said Edwin Nuwagira Rinah Arinaitwe Rhina Mushagara Peter Buzaare Anna Chongolo Samuel Jjunju Precious Twesigye Megan Null Tania A Thomas Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial BMJ Open |
| title | Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial |
| title_full | Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial |
| title_fullStr | Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial |
| title_full_unstemmed | Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial |
| title_short | Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial |
| title_sort | early empiric anti mycobacterium tuberculosis therapy for sepsis in sub saharan africa a protocol of a randomised clinical trial |
| url | https://bmjopen.bmj.com/content/12/6/e061953.full |
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