Clinical trial NCT06658002: Fungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A
Official title: Fungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Fungal Keratitis
Corneal Ulcer
Keywords: Corneal Ulcer
Cyclosporine A
Fungal Keratitis
Fungal Corneal Ulcer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Aravind Eye Hospitals, India
name: Aravind Eye Care System
First posted: 2024-10-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This is a randomized controlled trial in which 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% or CsA 2% or placebo for 4 weeks. In cases of bilateral fungal keratitis, if both eyes fit inclusion criteria, the eye with worse acuity will be randomized.

The primary outcome is Best Corrected Visual Acuity (BCVA) at 3 months.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: 3 months (12 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Farncisco
state: California
city: Pondicherry
country: India
facility: Aravind Eye Institute
state: Tamil Nadu
Study officials:
affiliation: UCSF Proctor Foundation
name: Gerami D Seitzman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.