Fungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Cyclosporine A, Placebo Comparator: Placebo.
- Who it may be relevant to
- Registry conditions: Fungal Keratitis, Corneal Ulcer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, India
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Detailed description
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.
Interventions
- Drug 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. - Other 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.
Primary outcome measures
- Best Spectacle Corrected Visual Acuity (BSCVA) [Time frame: 12 weeks]
Secondary outcome measures (4)
- Corneal Scar Size [Time frame: 12 weeks]
- Corneal Perforation Rate [Time frame: 12 weeks]
- Corneal Ulcer Re-epithelialization [Time frame: 12 weeks]
- Microbiologic Cure Rate [Time frame: 12 weeks]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Factorial
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 1 center
- University of California, San Farncisco — San Francisco
India · 1 center
- Aravind Eye Institute — Pondicherry
Publications
- 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
Identifiers
NCT: NCT06658002 · 24-41971