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Cross-linking for Corneal Ulcers Treatment Trial (CLAIR)

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ClinicalTrials.gov Identifier: NCT02570321
Recruitment Status : Recruiting
First Posted : October 7, 2015
Last Update Posted : November 14, 2019
Sponsor:
Collaborator:
Aravind Eye Hospitals, India
Information provided by (Responsible Party):
University of California, San Francisco

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.


Condition or disease Intervention/treatment Phase
Corneal Ulcer Infectious Keratitis Bacterial Ulcer Fungal Ulcer Procedure: Bacterial ulcer cross-linking Procedure: Bacterial ulcer control Procedure: Fungal ulcer cross-linking Procedure: Fungal ulcer control Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cross-linking for Corneal Ulcers Treatment Trial
Actual Study Start Date : November 2015
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: Bacterial ulcer cross-linking
Standard of care topical treatment for bacterial ulcer plus cross-linking
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.

Active Comparator: Bacterial ulcer control
Standard of care topical treatment for bacterial ulcer
Procedure: 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.

Experimental: Fungal ulcer cross-linking plus natamycin
Standard of care topical treatment for fungal ulcer with natamycin plus cross-linking
Procedure: 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.


Active Comparator: Fungal ulcer control with natamycin
Standard of care topical treatment for fungal ulcer with natamycin
Procedure: 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.


Experimental: Fungal ulcer cross-linking plus amphotericin
Standard of care topical treatment for fungal ulcer with amphotericin plus cross-linking
Procedure: 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.


Active Comparator: Fungal ulcer control with amphotericin
Standard of care topical treatment for fungal ulcer with amphotericin
Procedure: 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.





Primary Outcome Measures :
  1. Microbiological cure on repeat culture [ Time Frame: 4 to 24 hours after enrollment ]

Secondary Outcome Measures :
  1. Best spectacle-corrected visual acuity [ Time Frame: 12 months ]
  2. Scar size [ Time Frame: 12 months ]
    Measured by clinical exam

  3. Adverse events including rate of perforation/need for therapeutic penetrating keratoplasty [ Time Frame: 12 months ]
  4. Corneal thinning [ Time Frame: 12 months ]
    As measured on Pentacam

  5. Topography [ Time Frame: 12 months ]
    As measured on Pentacam

  6. Corneal Higher Order Aberrations [ Time Frame: 12 months ]
    As measured on Pentacam

  7. Vision related quality of life [ Time Frame: 3 months ]
    As measured by the Indian Visual Function Questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02570321


Contacts
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Contact: Jennifer R Rose-Nussbaumer, MD 415-502-2666 Jennifer.Rose-Nussbaumer@ucsf.edu
Contact: Ariana Austin, MS 415-502-0275 ariana.austin@ucsf.edu

Locations
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United States, California
Proctor Foundation, UCSF Active, not recruiting
San Francisco, California, United States, 94143
India
Aravind Eye Hospitals Recruiting
Madurai, Tamil Nadu, India
Contact: NV Prajna, DNB, FRC Ophth    +91 452 435 6100    prajna@aravind.org   
Principal Investigator: NV Prajna, DNB, FRC Ophth         
Sponsors and Collaborators
University of California, San Francisco
Aravind Eye Hospitals, India
Investigators
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Principal Investigator: Jennifer R Rose-Nussbaumer, MPH University of California, San Francisco
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02570321    
Other Study ID Numbers: 14-14918
First Posted: October 7, 2015    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: November 2019
Keywords provided by University of California, San Francisco:
Cornea
Ulcer
Infectious keratitis
Bacterial
Fungal
Additional relevant MeSH terms:
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Communicable Diseases
Infection
Corneal Ulcer
Keratitis
Ulcer
Pathologic Processes
Corneal Diseases
Eye Diseases
Eye Infections