Fungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A

Обзор

The goal of this clinical trial is to learn if adjunctive topical Cyclosporine A eye drops combined with standard of care topical Natamycin treatment improves vision outcomes in patients with fungal keratitis.

Подробное описание

This is a randomized, masked, clinical trial of patients with documented fungal infections of the cornea. In this trial participants are treated with (standard of care) topical natamycin for a minimum of 48 hours and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1%, or CsA 2%, or placebo for 4 weeks. Natamycin will be continued until the corneal ulcer has resolved. The primary outcome of this pilot trial is best corrected visual acuity (BCVA) at 3 months. The specific aims of this trial are to:

* to determine if early use of topical cyclosporine A is a beneficial adjuvant to natamycin in the treatment of mild to moderate fungal keratitis. * to determine if adjunctive 2% cyclosporine A demonstrates greater efficacy than 0.1% cyclosporine A in the treatment of fungal keratitis. * to determine which ulcer characteristics, predict the most benefit from the addition of early topical cyclosporine.

In this study the investigators will partner with their cornea colleagues at the Aravind Eye Hospital. This is because the incidence of fungal corneal ulcers is among the highest in the world in this location.

Вмешательства

• Препарат Cyclosporine A
  Participants with smear or culture proven fungal keratitis are treated for a minimum of 48 hours with topical natamycin and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1%, 2% or placebo for 4 weeks. Natamycin is continued until the ulcer has healed.
• Другое Placebo Comparator: Placebo
  Participants with smear or culture proven fungal keratitis are treated for a minimum of 48 hours with topical natamycin and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1%, 2% or placebo for 4 weeks. Natamycin is continued until the ulcer has healed.

Первичные конечные точки

• Best Spectacle Corrected Visual Acuity (BSCVA) [Срок оценки: 12 weeks]

Вторичные конечные точки (4)

• Corneal Scar Size [Срок оценки: 12 weeks]
• Corneal Perforation Rate [Срок оценки: 12 weeks]
• Corneal Ulcer Re-epithelialization [Срок оценки: 12 weeks]
• Microbiologic Cure Rate [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• Inclusion is based on presenting acuity, not ulcer size.
• Inclusion of 20/40 = 6/12 = 0.3 Log MAR and 20/400 = 3/60 = +1.3 Log MAR.
• Smear or culture positive for fungal keratitis, any length.
• Age 18 years.
• Willing to participate in study.

Критерии исключения

• Co-infection with bacterial or viral keratitis.
• Corneal perforation.
• Requiring therapeutic keratoplasty for fungal keratitis.
• Unwilling or unable to follow up (e.g., living too far from hospital).
• Presenting acuity better than 20/40 = 6/12 = 0.3 Log MAR or worse than 20/400 = 3/60 = +1.3 Log MAR.
• Subjects taking cyclosporine at any concentration on presentation.
• Acuity worse than 20/200 = 6/60 = +1.0 Log MAR in unaffected eye.
• Pregnant women.
• Penetrating Keratoplasty.
• Presents with a 0-7 day history of topical steroid.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California, San Farncisco — San Francisco

Индия · 1 центр

• Aravind Eye Institute — Pondicherry

Публикации

• Chatterjee S, Agrawal D. Use of Topical Cyclosporine 0.1% in Therapeutic Penetrating Keratoplasty for Fungal Keratitis. Cornea. 2022 Sep 1;41(9):1116-1121. doi: 10.1097/ICO.0000000000002827. Epub 2021 Sep 3. PMID 34483271
• Kauss Hornecker M, Charles Weber S, Brandely Piat ML, Darrodes M, Jomaa K, Chast F. [Cyclosporine eye drops: A 4-year retrospective study (2009-2013)]. J Fr Ophtalmol. 2015 Oct;38(8):700-8. doi: 10.1016/j.jfo.2015.02.008. Epub 2015 Sep 11. French. PMID 26371985
• Bell NP, Karp CL, Alfonso EC, Schiffman J, Miller D. Effects of methylprednisolone and cyclosporine A on fungal growth in vitro. Cornea. 1999 May;18(3):306-13. doi: 10.1097/00003226-199905000-00012. PMID 10336034
• Perry HD, Doshi SJ, Donnenfeld ED, Bai GS. Topical cyclosporin A in the management of therapeutic keratoplasty for mycotic keratitis. Cornea. 2002 Mar;21(2):161-3. doi: 10.1097/00003226-200203000-00006. PMID 11862086
• Cordeiro RA, Macedo RB, Teixeira CEC, Marques FJF, Bandeira TJPG, Moreira JLB, Brilhante RSN, Rocha MFG, Sidrim JJC. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex. J Med Microbiol. 2014 Jul;63(Pt 7):936-944. doi: 10.1099/jmm.0.073478-0. Epub 2014 Apr 10. PMID 24722799
• Survase SA, Kagliwal LD, Annapure US, Singhal RS. Cyclosporin A--a review on fermentative production, downstream processing and pharmacological applications. Biotechnol Adv. 2011 Jul-Aug;29(4):418-35. doi: 10.1016/j.biotechadv.2011.03.004. Epub 2011 Apr 5. PMID 21447377

Идентификаторы

NCT: NCT06658002 · 24-41971

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗