Cross-linking for Corneal Ulcers Treatment Trial

NCT02570321 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 14-14918
• Study Type: interventional
• Target: 147
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Corneal Ulcer; Infectious Keratitis; Bacterial Ulcer; Fungal Ulcer

Keywords

Cornea; Ulcer; Infectious keratitis; Bacterial; Fungal

Outcome Measures

Primary Outcomes (1)

• Microbiological Cure on Repeat Culture

  Corneal scraping of the ulcer will be performed and directly inoculated on to sheep's blood agar, chocolate agar, potato dextrose agar or Sabouraud's agar for bacterial and fungal culture. Microbiological cure is defined as no growth of bacteria or fungus on these media.

  4 to 24 hours after enrollment

Secondary Outcomes (3)

• Best Spectacle-corrected Visual Acuity

  3 months

• Scar Size

  3 months

• Adverse Events Including Rate of Perforation/Need for Therapeutic Penetrating Keratoplasty

  3 months

Other Outcomes (1)

• Vision Related Quality of Life

  3 months

Study Arms (6)

Bacterial ulcer cross-linking

EXPERIMENTAL

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

Procedure: Corneal Cross-linking

Bacterial ulcer control

ACTIVE COMPARATOR

Standard of care topical treatment for bacterial ulcer

Procedure: Corneal Cross-linking

Fungal ulcer cross-linking plus natamycin

EXPERIMENTAL

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

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

Fungal ulcer control with natamycin

ACTIVE COMPARATOR

Standard of care topical treatment for fungal ulcer with natamycin

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

Fungal ulcer cross-linking plus amphotericin

EXPERIMENTAL

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

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

Fungal ulcer control with amphotericin

ACTIVE COMPARATOR

Standard of care topical treatment for fungal ulcer with amphotericin

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

Interventions

Corneal Cross-linking PROCEDURE

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; Bacterial ulcer cross-linking; Fungal ulcer control with amphotericin; Fungal ulcer control with natamycin; Fungal ulcer cross-linking plus amphotericin; Fungal ulcer cross-linking plus natamycin

Anti Fungal Drug DRUG

Topical Amphotericin B vs Topical Natamycin

Fungal ulcer control with amphotericin; Fungal ulcer control with natamycin; Fungal ulcer cross-linking plus amphotericin; Fungal ulcer cross-linking plus natamycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Aravind Eye Hospitals, India: collaborator

Study Sites (2)

Proctor Foundation, UCSF

San Francisco, California, 94143, United States

Location

Aravind Eye Hospitals

Madurai, Tamil Nadu, India

Location

Related Publications (6)

• Prajna NV, Radhakrishnan N, Lalitha P, Liu Z, Keenan JD, Arnold BF, Rose-Nussbaumer J. Mediators of the Effect of Corneal Cross-Linking on Visual Acuity for Fungal Ulcers: A Prespecified Secondary Analysis From the Cross-Linking-Assisted Infection Reduction Trial. Cornea. 2022 Oct 1;41(10):1217-1221. doi: 10.1097/ICO.0000000000002965. Epub 2022 Jan 17.

  PMID: 35044972 DERIVED

• Prajna NV, Lalitha P, Krishnan T, Rajaraman R, Radnakrishnan N, Srinivasan M, Devi L, Das M, Liu Z, Zegans ME, Acharya NR, Porco TC, Lietman TM, Rose-Nussbaumer J. Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India: A Post Hoc Analysis of 3 Randomized Clinical Trials. JAMA Ophthalmol. 2022 Feb 1;140(2):179-184. doi: 10.1001/jamaophthalmol.2021.5765.

  PMID: 35024776 DERIVED

• Prajna NV, Radhakrishnan N, Lalitha P, Rajaraman R, Narayana S, Austin AF, Liu Z, Keenan JD, Porco TC, Lietman TM, Rose-Nussbaumer J. Cross-Linking Assisted Infection Reduction (CLAIR): A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Bacterial Keratitis. Cornea. 2021 Jul 1;40(7):837-841. doi: 10.1097/ICO.0000000000002510.

  PMID: 33079921 DERIVED

• Prajna NV, Radhakrishnan N, Lalitha P, Austin A, Liu Z, Keenan JD, Porco TC, Lietman TM, Rose-Nussbaumer J. Cross-Linking Assisted Infection Reduction: One-year Follow-up of a Randomized Clinical Trial Evaluating Cross-Linking for Fungal Keratitis. Ophthalmology. 2021 Jun;128(6):950-952. doi: 10.1016/j.ophtha.2020.09.042. Epub 2020 Oct 5. No abstract available.

  PMID: 33031809 DERIVED

• Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.

  PMID: 32557558 DERIVED

• Prajna NV, Radhakrishnan N, Lalitha P, Austin A, Ray KJ, Keenan JD, Porco TC, Lietman TM, Rose-Nussbaumer J. Cross-Linking-Assisted Infection Reduction: A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Outcomes in Fungal Keratitis. Ophthalmology. 2020 Feb;127(2):159-166. doi: 10.1016/j.ophtha.2019.08.029. Epub 2019 Sep 4.

  PMID: 31619359 DERIVED

MeSH Terms

Conditions

Corneal Ulcer; Corneal Diseases; Ulcer

Interventions

Corneal Cross-Linking

Condition Hierarchy (Ancestors)

Eye Infections; Infections; Keratitis; Eye Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Photochemotherapy; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Results Point of Contact

• Title: Sarah Abedelrahman, Research Data Analyst
• Organization: UCSF, Proctor Foundation

sarah.abdelrahman@ucsf.edu

2135093817

Study Officials

• Jennifer R Rose-Nussbaumer, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with corneal ulcers are randomized to topical antimicrobial plus corneal crosslinking versus topical antimicrobial alone

Study Record Dates

• First Submitted: September 15, 2015
• First Posted: October 7, 2015
• Study Start: November 1, 2015
• Primary Completion: June 18, 2018
• Study Completion: March 19, 2019
• Last Updated: June 18, 2025
• Results First Posted: August 27, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); US (1)