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Cross-linking for Corneal Ulcers Treatment Trial (CLAIR)

Primary Purpose

Corneal Ulcer, Infectious Keratitis, Bacterial Ulcer

Status
Unknown status
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Bacterial ulcer cross-linking
Bacterial ulcer control
Fungal ulcer cross-linking
Fungal ulcer control
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corneal Ulcer focused on measuring Cornea, Ulcer, Infectious keratitis, Bacterial, Fungal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Proctor Foundation, UCSF
  • Aravind Eye HospitalsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Bacterial ulcer cross-linking

Bacterial ulcer control

Fungal ulcer cross-linking plus natamycin

Fungal ulcer control with natamycin

Fungal ulcer cross-linking plus amphotericin

Fungal ulcer control with amphotericin

Arm Description

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

Standard of care topical treatment for bacterial ulcer

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

Standard of care topical treatment for fungal ulcer with natamycin

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

Standard of care topical treatment for fungal ulcer with amphotericin

Outcomes

Primary Outcome Measures

Microbiological cure on repeat culture

Secondary Outcome Measures

Best spectacle-corrected visual acuity
Scar size
Measured by clinical exam
Adverse events including rate of perforation/need for therapeutic penetrating keratoplasty
Corneal thinning
As measured on Pentacam
Topography
As measured on Pentacam
Corneal Higher Order Aberrations
As measured on Pentacam
Vision related quality of life
As measured by the Indian Visual Function Questionnaire

Full Information

First Posted
September 15, 2015
Last Updated
November 12, 2019
Sponsor
University of California, San Francisco
Collaborators
Aravind Eye Hospitals, India
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1. Study Identification

Unique Protocol Identification Number
NCT02570321
Brief Title
Cross-linking for Corneal Ulcers Treatment Trial
Acronym
CLAIR
Official Title
Cross-linking for Corneal Ulcers Treatment Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 2015 (Actual)
Primary Completion Date
November 2020 (Anticipated)
Study Completion Date
November 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Aravind Eye Hospitals, India

4. Oversight

Data Monitoring Committee
No

5. Study Description

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: collagen cross-linking + amphotericin; collagen cross-linking + natamycin; amphotericin alone; 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Ulcer, Infectious Keratitis, Bacterial Ulcer, Fungal Ulcer
Keywords
Cornea, Ulcer, Infectious keratitis, Bacterial, Fungal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
266 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bacterial ulcer cross-linking
Arm Type
Experimental
Arm Description
Standard of care topical treatment for bacterial ulcer plus cross-linking
Arm Title
Bacterial ulcer control
Arm Type
Active Comparator
Arm Description
Standard of care topical treatment for bacterial ulcer
Arm Title
Fungal ulcer cross-linking plus natamycin
Arm Type
Experimental
Arm Description
Standard of care topical treatment for fungal ulcer with natamycin plus cross-linking
Arm Title
Fungal ulcer control with natamycin
Arm Type
Active Comparator
Arm Description
Standard of care topical treatment for fungal ulcer with natamycin
Arm Title
Fungal ulcer cross-linking plus amphotericin
Arm Type
Experimental
Arm Description
Standard of care topical treatment for fungal ulcer with amphotericin plus cross-linking
Arm Title
Fungal ulcer control with amphotericin
Arm Type
Active Comparator
Arm Description
Standard of care topical treatment for fungal ulcer with amphotericin
Intervention Type
Procedure
Intervention Name(s)
Bacterial ulcer cross-linking
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Bacterial ulcer control
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Fungal ulcer cross-linking
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Fungal ulcer control
Intervention Description
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.
Primary Outcome Measure Information:
Title
Microbiological cure on repeat culture
Time Frame
4 to 24 hours after enrollment
Secondary Outcome Measure Information:
Title
Best spectacle-corrected visual acuity
Time Frame
12 months
Title
Scar size
Description
Measured by clinical exam
Time Frame
12 months
Title
Adverse events including rate of perforation/need for therapeutic penetrating keratoplasty
Time Frame
12 months
Title
Corneal thinning
Description
As measured on Pentacam
Time Frame
12 months
Title
Topography
Description
As measured on Pentacam
Time Frame
12 months
Title
Corneal Higher Order Aberrations
Description
As measured on Pentacam
Time Frame
12 months
Title
Vision related quality of life
Description
As measured by the Indian Visual Function Questionnaire
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer R Rose-Nussbaumer, MD
Phone
415-502-2666
Email
Jennifer.Rose-Nussbaumer@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Ariana Austin, MS
Phone
415-502-0275
Email
ariana.austin@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer R Rose-Nussbaumer, MPH
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Proctor Foundation, UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Aravind Eye Hospitals
City
Madurai
State/Province
Tamil Nadu
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
NV Prajna, DNB, FRC Ophth
Phone
+91 452 435 6100
Email
prajna@aravind.org
First Name & Middle Initial & Last Name & Degree
NV Prajna, DNB, FRC Ophth

12. IPD Sharing Statement

Citations:
PubMed Identifier
35044972
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.
Results Reference
derived
PubMed Identifier
35024776
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.
Results Reference
derived
PubMed Identifier
33079921
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.
Results Reference
derived
PubMed Identifier
33031809
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.
Results Reference
derived
PubMed Identifier
32557558
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.
Results Reference
derived
PubMed Identifier
31619359
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.
Results Reference
derived

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Cross-linking for Corneal Ulcers Treatment Trial

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