Fungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A

Phase 3

Not yet recruiting

• Conditions: Fungal Keratitis; Corneal Ulcer
• Interventions: Drug: Cyclosporine A

• Registration Number: NCT06658002
• Lead Sponsor: University of California, San Francisco

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.

Study Timeline

• Study First Submitted: 2024-10-23
• Study First Submitted QC: 2024-10-23
• Study First Posted: 2024-10-26
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Study Start: 2025-06-01
• Primary Completion: 2027-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 150

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Cyclosporine A (CsA) 0.1%	Cyclosporine A	After one week of hourly natamycin eye drops the participants in this arm will use this drop four times a day for one month then twice a day for one month.
Cyclosporine A (CsA) 2%	Cyclosporine A	After one week of hourly natamycin eye drops the participants in this arm will use this drop four times a day for one month then twice a day for one month.

Primary Outcome Measures

Name	Time	Method
Best Corrected Visual Acuity (BCVA)	3 months (12 weeks)

Trial Locations

Locations (2)

University of California, San Farncisco; 🇺🇸 San Francisco, California, United States

Aravind Eye Institute; 🇮🇳 Pondicherry, Tamil Nadu, India