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 tre...
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BMJ Publishing Group
2020-09-01
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| author | Victor Hu David Macleod Helen Anne Weiss Matthew J Burton Simon Arunga Astrid Leck Sanjay Kumar Singh Jeremy John Hoffman Reena Yadav Sandip Das Sanyam Pankaj Chaudhary Abhishek Roshan Einoti Matayan |
| author_facet | Victor Hu David Macleod Helen Anne Weiss Matthew J Burton Simon Arunga Astrid Leck Sanjay Kumar Singh Jeremy John Hoffman Reena Yadav Sandip Das Sanyam Pankaj Chaudhary Abhishek Roshan Einoti Matayan |
| author_sort | Victor Hu |
| collection | DOAJ |
| description | 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 |
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| institution | Kabale University |
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| language | English |
| publishDate | 2020-09-01 |
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| spelling | doaj-art-7667b167dc774ab3b3442b02fe8f50872025-01-08T11:25:10ZengBMJ Publishing GroupBMJ Open2044-60552020-09-0110910.1136/bmjopen-2020-038066Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trialVictor Hu0David Macleod1Helen Anne Weiss2Matthew J Burton3Simon Arunga4Astrid Leck5Sanjay Kumar Singh6Jeremy John Hoffman7Reena Yadav8Sandip Das Sanyam9Pankaj Chaudhary10Abhishek Roshan11Einoti Matayan12St Paul`s Eye Unit, Liverpool, UK17 Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK15 Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UKClinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UKMbarara University of Science and Technology Faculty of Medicine, Mbarara, UgandaDepartment of Infectious and Tropical Diseases, LSHTM, London, UKPaediatric Ophthalmology, Sagarmatha Choudhary Eye Hospital, Lahan, NepalNational Institute of Health Research (NIHR) Biomedical Research Centre, University College London Institute of Ophthalmology, London, UKCornea Department, Sagarmatha Choudhary Eye Hospital, Lahan, NepalCornea Department, Sagarmatha Choudhary Eye Hospital, Lahan, NepalCornea Department, Sagarmatha Choudhary Eye Hospital, Lahan, NepalCornea Department, Sagarmatha Choudhary Eye Hospital, Lahan, NepalDepartment of Ophthalmology, Kilimanjaro Christian Medical Centre, Moshi, TanzaniaIntroduction 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.https://bmjopen.bmj.com/content/10/9/e038066.full |
| spellingShingle | Victor Hu David Macleod Helen Anne Weiss Matthew J Burton Simon Arunga Astrid Leck Sanjay Kumar Singh Jeremy John Hoffman Reena Yadav Sandip Das Sanyam Pankaj Chaudhary Abhishek Roshan Einoti Matayan 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 |
| 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_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_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_sort | topical chlorhexidine 0 2 versus topical natamycin 5 for fungal keratitis in nepal rationale and design of a randomised controlled non inferiority trial |
| url | https://bmjopen.bmj.com/content/10/9/e038066.full |
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