Cross-linking for Corneal Ulcers Treatment Trial

Corneal Ulcer Clinical Trial

— CLAIR  

Official title:

Cross-linking for Corneal Ulcers Treatment Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02570321
• Other study ID #: 14-14918
• Status: Recruiting
• Phase: Phase 4
• Start date: November 2015
• Est. completion date: November 2020

Study information

• Verified date: November 2019
• Source: University of California, San Francisco
• Contact: Jennifer R Rose-Nussbaumer, MD
• Phone: 415-502-2666
• Email: Jennifer.Rose-Nussbaumer[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 266
• Est. completion date: November 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bacterial Ulcer
• Communicable Diseases
• Corneal Ulcer
• Fungal Ulcer
• Infection
• Infectious Keratitis
• Keratitis
• Ulcer

Intervention

Procedure:
• Bacterial ulcer cross-linking
For those subjects randomized to receive collagen cross-linking, the procedure will be performed as per the routine at the hospital (UV-X machine; strict aseptic precautions; corneal epithelium debrided and 0.1% riboflavin applied for 30 minutes, then UV-A radiation applied for 30 minutes at 370nm with 3mW/cm2). Corneal cross-linking is a routine procedure performed by Aravind Eye Hospital for infectious keratitis.
• Bacterial ulcer control
For those bacterial ulcer subjects randomized to the control group, they will receive the standard of care topical treatment for bacterial ulcers. This group will have their eyes irrigated with a balanced salt solution.
• Fungal ulcer cross-linking
Prior to receiving cross-linking, topical amphotericin B or topical natamycin antifungal therapy will be started as per routine at the hospital; a loading dose of amphotericin B or natamycin every 5 minutes x 6 will be followed by dosing every 30 minutes. Amphotericin B and natamycin are routinely used therapies for fungal keratitis at Aravind Eye Hospital. For those subjects randomized to receive collagen cross-linking, the procedure will be performed as per the routine at the hospital (UV-X machine; strict aseptic precautions; corneal epithelium debrided and 0.1% riboflavin applied for 30 minutes, then UV-A radiation applied for 30 minutes at 370nm with 3mW/cm2). Corneal cross-linking is a routine procedure performed by Aravind Eye Hospital for infectious keratitis.
• Fungal ulcer control
Prior to receiving sham cross-linking, topical amphotericin B or topical natamycin antifungal therapy will be started as per routine at the hospital; a loading dose of amphotericin B or natamycin every 5 minutes x 6 will be followed by dosing every 30 minutes. Amphotericin B and natamycin are routinely used therapies for fungal keratitis at Aravind Eye Hospital. For those fungal ulcer subjects randomized to the control group, they will receive the standard of care topical treatment for fungal ulcers. This group will have their eyes irrigated with a balanced salt solution.

Locations

Country	Name	City	State
India	Aravind Eye Hospitals	Madurai	Tamil Nadu
United States	Proctor Foundation, UCSF	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Aravind Eye Hospitals, India

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiological cure on repeat culture		4 to 24 hours after enrollment
Secondary	Best spectacle-corrected visual acuity		12 months
Secondary	Scar size	Measured by clinical exam	12 months
Secondary	Adverse events including rate of perforation/need for therapeutic penetrating keratoplasty		12 months
Secondary	Corneal thinning	As measured on Pentacam	12 months
Secondary	Topography	As measured on Pentacam	12 months
Secondary	Corneal Higher Order Aberrations	As measured on Pentacam	12 months
Secondary	Vision related quality of life	As measured by the Indian Visual Function Questionnaire	3 months