Cross-linking for Corneal Ulcers Treatment Trial (CLAIR)

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 3

Conditions: Bacterial Ulcer; Corneal Ulcer; Fungal Ulcer; Infectious Keratitis

Treatments: Drug: Anti Fungal Drug; Procedure: Corneal Cross-linking

Study type: Interventional

Funder types: Other

Identifiers

NCT02570321

14-14918

Details and patient eligibility

About

The primary purpose of this study is to determine if patients randomized to corneal collagen cross-linking plus medical therapy will have a lower prevalence of positive bacterial or fungal cultures immediately after the procedure than patients who received medical therapy alone.

The secondary purpose of this study is to determine if patients randomized to corneal collagen cross-linking will have a better visual acuity at 3 and 12 months than patients who receive medical therapy alone.

Full description

The proposed study is a randomized controlled trial to determine whether collagen cross-linking improves outcomes in microbial keratitis. Patients presenting to the Aravind Eye Hospitals in Madurai, India for treatment of microbial keratitis will be recruited for the proposed study. Approximately 266 patients will be enrolled in the study. Subjects presenting with bacterial keratitis will be randomized to receive medical therapy plus corneal collagen cross-linking at presentation or to receive medical therapy alone. All subjects with bacterial ulcers will receive standard topical antibiotic medications as required after the procedure.

Subjects with fungal keratitis will be randomized into one of four groups:

1. collagen cross-linking + amphotericin;
2. collagen cross-linking + natamycin;
3. amphotericin alone;
4. natamycin alone.

All study subjects will be followed for 12 months to evaluate response to treatment.

Investigators from the University of California, San Francisco (UCSF) will assist Aravind Eye Hospital with the study design, implementation, and analysis of the research, and will help fund the study. The investigators plan to visit Aravind to help with the study implementation. UCSF will play an important role in this study by assisting with the study design, implementation, analysis, and funding.

Enrollment: 147 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Corneal ulcer that is smear positive for either bacteria or filamentous fungus
• Pinhole visual acuity worse than 20/70 in the affected eye
• Not treated already with antimicrobial medications at presentation
• Age over 18 years
• Basic understanding of the study as determined by the physician
• Commitment to return for follow up visits

Exclusion criteria

• Evidence of concomitant infection on exam or gram stain (i.e. herpes, both bacteria and acanthamoeba on gram stain)
• Impending or frank perforation at recruitment
• Involvement of sclera at presentation
• Non-infectious or autoimmune keratitis
• History of corneal transplantation or recent intraocular surgery
• No light perception in the affected eye
• Pinhole visual acuity worse than 20/200 in the unaffected eye
• Participants who are decisionally and/or cognitively impaired

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

147 participants in 6 patient groups

Bacterial ulcer cross-linking

Experimental group

Description:

Standard of care topical treatment for bacterial ulcer plus cross-linking

Treatment:

Procedure: Corneal Cross-linking

Bacterial ulcer control

Active Comparator group

Description:

Standard of care topical treatment for bacterial ulcer

Treatment:

Procedure: Corneal Cross-linking

Fungal ulcer cross-linking plus natamycin

Experimental group

Description:

Standard of care topical treatment for fungal ulcer with natamycin plus cross-linking

Treatment:

Procedure: Corneal Cross-linking

Drug: Anti Fungal Drug

Fungal ulcer control with natamycin

Active Comparator group

Description:

Standard of care topical treatment for fungal ulcer with natamycin

Treatment:

Procedure: Corneal Cross-linking

Drug: Anti Fungal Drug

Fungal ulcer cross-linking plus amphotericin

Experimental group

Description:

Standard of care topical treatment for fungal ulcer with amphotericin plus cross-linking

Treatment:

Procedure: Corneal Cross-linking

Drug: Anti Fungal Drug

Fungal ulcer control with amphotericin

Active Comparator group

Description:

Standard of care topical treatment for fungal ulcer with amphotericin

Treatment:

Procedure: Corneal Cross-linking

Drug: Anti Fungal Drug