Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial
Abstract Background Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patien...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-10-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13063-017-2199-6 |
| _version_ | 1811299575252647936 |
|---|---|
| author | Sunil Pokharel Buddha Basnyat Amit Arjyal Saruna Pathak Mahat Raj Kumar KC Abhusani Bhuju Buddhi Poudyal Evelyne Kestelyn Ritu Shrestha Dung Nguyen Thi Phuong Rajkumar Thapa Manan Karki Sabina Dongol Abhilasha Karkey Marcel Wolbers Stephen Baker Guy Thwaites |
| author_facet | Sunil Pokharel Buddha Basnyat Amit Arjyal Saruna Pathak Mahat Raj Kumar KC Abhusani Bhuju Buddhi Poudyal Evelyne Kestelyn Ritu Shrestha Dung Nguyen Thi Phuong Rajkumar Thapa Manan Karki Sabina Dongol Abhilasha Karkey Marcel Wolbers Stephen Baker Guy Thwaites |
| author_sort | Sunil Pokharel |
| collection | DOAJ |
| description | Abstract Background Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI. Methods/design This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients. Discussion Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever. Trial registration ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016. |
| first_indexed | 2024-04-13T06:37:54Z |
| format | Article |
| id | doaj.art-d9080f16f7bd4b21b16c85d0e5323706 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-13T06:37:54Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-d9080f16f7bd4b21b16c85d0e53237062022-12-22T02:57:51ZengBMCTrials1745-62152017-10-0118111310.1186/s13063-017-2199-6Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trialSunil Pokharel0Buddha Basnyat1Amit Arjyal2Saruna Pathak Mahat3Raj Kumar KC4Abhusani Bhuju5Buddhi Poudyal6Evelyne Kestelyn7Ritu Shrestha8Dung Nguyen Thi Phuong9Rajkumar Thapa10Manan Karki11Sabina Dongol12Abhilasha Karkey13Marcel Wolbers14Stephen Baker15Guy Thwaites16Oxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesPatan Hospital, Patan Academy of Health SciencesCentre for Tropical Medicine and Global Health, University of OxfordOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research UnitPatan Hospital, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesOxford University Clinical Research Unit Nepal, Patan Academy of Health SciencesCentre for Tropical Medicine and Global Health, University of OxfordCentre for Tropical Medicine and Global Health, University of OxfordCentre for Tropical Medicine and Global Health, University of OxfordAbstract Background Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI. Methods/design This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients. Discussion Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever. Trial registration ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016.http://link.springer.com/article/10.1186/s13063-017-2199-6Undifferentiated febrile illnessEnteric feverAzithromycinCo-trimoxazoleFever clearance time |
| spellingShingle | Sunil Pokharel Buddha Basnyat Amit Arjyal Saruna Pathak Mahat Raj Kumar KC Abhusani Bhuju Buddhi Poudyal Evelyne Kestelyn Ritu Shrestha Dung Nguyen Thi Phuong Rajkumar Thapa Manan Karki Sabina Dongol Abhilasha Karkey Marcel Wolbers Stephen Baker Guy Thwaites Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial Trials Undifferentiated febrile illness Enteric fever Azithromycin Co-trimoxazole Fever clearance time |
| title | Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial |
| title_full | Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial |
| title_fullStr | Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial |
| title_full_unstemmed | Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial |
| title_short | Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial |
| title_sort | co trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in nepal study protocol for a randomized controlled trial |
| topic | Undifferentiated febrile illness Enteric fever Azithromycin Co-trimoxazole Fever clearance time |
| url | http://link.springer.com/article/10.1186/s13063-017-2199-6 |
| work_keys_str_mv | AT sunilpokharel cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT buddhabasnyat cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT amitarjyal cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT sarunapathakmahat cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT rajkumarkc cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT abhusanibhuju cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT buddhipoudyal cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT evelynekestelyn cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT ritushrestha cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT dungnguyenthiphuong cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT rajkumarthapa cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT manankarki cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT sabinadongol cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT abhilashakarkey cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT marcelwolbers cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT stephenbaker cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial AT guythwaites cotrimoxazoleversusazithromycinforthetreatmentofundifferentiatedfebrileillnessinnepalstudyprotocolforarandomizedcontrolledtrial |