Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial.
INTRODUCTION: Fungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line tr...
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Online Access: | https://researchonline.lshtm.ac.uk/id/eprint/4658059/ https://researchonline.lshtm.ac.uk/id/eprint/4658059/1/e038066.full-2.pdf |
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INTRODUCTION: Fungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively. METHODS AND ANALYSIS: We will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2-6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF). ETHICS AND DISSEMINATION: The Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ISRCTN14332621; pre-results. |
format |
Article in Journal/Newspaper |
author |
Hoffman, Jeremy John Yadav, Reena Das Sanyam, Sandip Chaudhary, Pankaj Roshan, Abhishek Singh, Sanjay Kumar Arunga, Simon Matayan, Einoti Macleod, David Weiss, Helen Anne Leck, Astrid Hu, Victor Burton, Matthew J |
spellingShingle |
Hoffman, Jeremy John Yadav, Reena Das Sanyam, Sandip Chaudhary, Pankaj Roshan, Abhishek Singh, Sanjay Kumar Arunga, Simon Matayan, Einoti Macleod, David Weiss, Helen Anne Leck, Astrid Hu, Victor Burton, Matthew J Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. |
author_facet |
Hoffman, Jeremy John Yadav, Reena Das Sanyam, Sandip Chaudhary, Pankaj Roshan, Abhishek Singh, Sanjay Kumar Arunga, Simon Matayan, Einoti Macleod, David Weiss, Helen Anne Leck, Astrid Hu, Victor Burton, Matthew J |
author_sort |
Hoffman, Jeremy John |
title |
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. |
title_short |
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. |
title_full |
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. |
title_fullStr |
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. |
title_full_unstemmed |
Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. |
title_sort |
topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in nepal: rationale and design of a randomised controlled non-inferiority trial. |
publisher |
BMJ |
publishDate |
2020 |
url |
https://researchonline.lshtm.ac.uk/id/eprint/4658059/ https://researchonline.lshtm.ac.uk/id/eprint/4658059/1/e038066.full-2.pdf |
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SCAR |
genre_facet |
SCAR |
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https://researchonline.lshtm.ac.uk/id/eprint/4658059/1/e038066.full-2.pdf Hoffman, Jeremy John <https://researchonline.lshtm.ac.uk/view/creators/icrujhof.html>; Yadav, Reena; Das Sanyam, Sandip; Chaudhary, Pankaj; Roshan, Abhishek; Singh, Sanjay Kumar; Arunga, Simon; Matayan, Einoti; Macleod, David <https://researchonline.lshtm.ac.uk/view/creators/lsh309648.html>; Weiss, Helen Anne <https://researchonline.lshtm.ac.uk/view/creators/eidehwei.html>; +3 more. Leck, Astrid <https://researchonline.lshtm.ac.uk/view/creators/icrualec.html>; Hu, Victor <https://researchonline.lshtm.ac.uk/view/creators/icruvihu.html>; Burton, Matthew J <https://researchonline.lshtm.ac.uk/view/creators/icrumbur.html>; (2020) Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. BMJ open, 10 (9). e038066-. ISSN 2044-6055 DOI: https://doi.org/10.1136/bmjopen-2020-038066 <https://doi.org/10.1136/bmjopen-2020-038066> |
op_rights |
cc_by_nc_nd |
op_rightsnorm |
CC-BY-NC-ND |
op_doi |
https://doi.org/10.1136/bmjopen-2020-038066 |
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BMJ Open |
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10 |
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ftlshtm:oai:researchonline.lshtm.ac.uk:4658059 2023-05-15T18:15:20+02:00 Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. Hoffman, Jeremy John Yadav, Reena Das Sanyam, Sandip Chaudhary, Pankaj Roshan, Abhishek Singh, Sanjay Kumar Arunga, Simon Matayan, Einoti Macleod, David Weiss, Helen Anne Leck, Astrid Hu, Victor Burton, Matthew J 2020-09-30 text https://researchonline.lshtm.ac.uk/id/eprint/4658059/ https://researchonline.lshtm.ac.uk/id/eprint/4658059/1/e038066.full-2.pdf en eng BMJ https://researchonline.lshtm.ac.uk/id/eprint/4658059/1/e038066.full-2.pdf Hoffman, Jeremy John <https://researchonline.lshtm.ac.uk/view/creators/icrujhof.html>; Yadav, Reena; Das Sanyam, Sandip; Chaudhary, Pankaj; Roshan, Abhishek; Singh, Sanjay Kumar; Arunga, Simon; Matayan, Einoti; Macleod, David <https://researchonline.lshtm.ac.uk/view/creators/lsh309648.html>; Weiss, Helen Anne <https://researchonline.lshtm.ac.uk/view/creators/eidehwei.html>; +3 more. Leck, Astrid <https://researchonline.lshtm.ac.uk/view/creators/icrualec.html>; Hu, Victor <https://researchonline.lshtm.ac.uk/view/creators/icruvihu.html>; Burton, Matthew J <https://researchonline.lshtm.ac.uk/view/creators/icrumbur.html>; (2020) Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial. BMJ open, 10 (9). e038066-. ISSN 2044-6055 DOI: https://doi.org/10.1136/bmjopen-2020-038066 <https://doi.org/10.1136/bmjopen-2020-038066> cc_by_nc_nd CC-BY-NC-ND Article NonPeerReviewed 2020 ftlshtm https://doi.org/10.1136/bmjopen-2020-038066 2022-03-03T07:31:24Z INTRODUCTION: Fungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively. METHODS AND ANALYSIS: We will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2-6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF). ETHICS AND DISSEMINATION: The Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ISRCTN14332621; pre-results. Article in Journal/Newspaper SCAR London School of Hygiene & Tropical Medicine: LSHTM Research Online BMJ Open 10 9 e038066 |