Clinical trial NCT02570321: Cross-linking for Corneal Ulcers Treatment Trial
Official title: Cross-linking for Corneal Ulcers Treatment Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Corneal Ulcer
Infectious Keratitis
Bacterial Ulcer
Fungal Ulcer
Keywords: Cornea
Ulcer
Infectious keratitis
Bacterial
Fungal
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Aravind Eye Hospitals, India
First posted: 2015-10-07
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with corneal ulcers are randomized to topical antimicrobial plus corneal crosslinking versus topical antimicrobial alone
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Microbiological Cure on Repeat Culture
timeFrame: 4 to 24 hours after enrollment
Secondary outcomes:
measure: Best Spectacle-corrected Visual Acuity
timeFrame: 3 months
measure: Scar Size
timeFrame: 3 months
measure: Adverse Events Including Rate of Perforation/Need for Therapeutic Penetrating Keratoplasty
timeFrame: 3 months
Other outcomes:
measure: Vision Related Quality of Life
timeFrame: 3 months
Locations:
city: San Francisco
country: United States
facility: Proctor Foundation, UCSF
state: California
city: Madurai
country: India
facility: Aravind Eye Hospitals
state: Tamil Nadu
Study officials:
affiliation: University of California, San Francisco
name: Jennifer R Rose-Nussbaumer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.