A Phase 3 interventional study of Corneal Cross-linking and Anti Fungal Drug in Corneal Ulcer, Infectious Keratitis and Bacterial Ulcer, sponsored by University of California, San Francisco. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-18.
Sponsored by University of California, San Francisco · Phase 3, Interventional, and Treatment
Among 22 studies in Corneal Ulcer with a site in United States — 4 open to participants now, 4 under way, 2 of them phase 3. Corneal Ulcer · United States.
Among the 22 studies in Corneal Ulcer with a site in United States, this one is the 11th largest by enrollment of the 19 interventional ones, is the only one that started in 2015, is one of 6 in phase 3, and was the 11th registered.
63 studies on the registry are indexed under Corneal Ulcer; 8 are open to participants now.
This study's enrollment of 147 is above the median of 60 across 45 interventional studies indexed under Corneal Ulcer.
Browse Corneal Ulcer studies →4 of the 22 studies in Corneal Ulcer with a site in United States are open now, in 4 countries. Each count lists the studies.
Of the 5 Corneal Ulcer studies recruiting now, 4 (80%) set no upper age limit and 1 (20%) stop at 75 or younger; 1 take children under 18; 0 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →22 studies; the count open now beside each. This study's row is marked.
First in 2002; this study’s year is marked. 1 started in 2015.
Median enrollment 150 across the 19 interventional studies, 55 across the 3 observational. Of the 14 that completed or were terminated, 8 (57%) have results posted.
5 of 22 have an industry lead sponsor. The 10 most frequent:
University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.
Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) have results posted.
University of California, San Francisco has 6 studies filed under Corneal Ulcer — fewer than ten, so there is no comparison to draw.
2 of the studies in Corneal Ulcer with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06658002Phase 3University of California, San FranciscoFungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A | 2027-09-01 |
| NCT05705024University of Illinois ChicagoEfficacy of Locally Delivered Allogeneic Mesenchymal Stromal Cells | 2026-12-28 |
Among the 22 studies in Corneal Ulcer with a site in United States, from their registry updates:
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.
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:
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard of care topical treatment for bacterial ulcer plus cross-linking
Procedure: Corneal Cross-linking
Standard of care topical treatment for bacterial ulcer
Procedure: Corneal Cross-linking
Standard of care topical treatment for fungal ulcer with natamycin plus cross-linking
Procedure: Corneal Cross-linking · Drug: Anti Fungal Drug
Standard of care topical treatment for fungal ulcer with natamycin
Procedure: Corneal Cross-linking · Drug: Anti Fungal Drug
Standard of care topical treatment for fungal ulcer with amphotericin plus cross-linking
Procedure: Corneal Cross-linking · Drug: Anti Fungal Drug
Standard of care topical treatment for fungal ulcer with amphotericin
Procedure: Corneal Cross-linking · Drug: Anti Fungal Drug
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.
Topical Amphotericin B vs Topical Natamycin
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.
Time frame: 4 to 24 hours after enrollment
Best Spectacle-corrected Visual Acuity
Best corrected visual acuity will be measured at baseline for both eyes using the standard ETDRS chart light box at the 4- and 1-meter test distances. In the case that the patient reads less than 10 letters at 4 meters, move the patient or the chart to a distance of 1 meter from the patient.
Time frame: 3 months
Scar Size
Study clinician will measure infiltrate or scar size using a standardized protocol with the slit lamp biomicroscope. The geometric mean of the scar size will be measured by recording the horizontal and vertical diameter.
Time frame: 3 months
Adverse Events Including Rate of Perforation/Need for Therapeutic Penetrating Keratoplasty
Adverse events include glaucoma, endophthalmitis, medication reaction, perforation including treatment by therapeutic penetrating keratoplasty.
Time frame: 3 months
Vision Related Quality of Life
Mobility subscale: As measured by the Indian Visual Function Questionnaire (IVFQ) which records quality of life on a scale of 0 to 100 with 100 representing the best quality of life.
Time frame: 3 months
| Milestone | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Started | 19 | 17 | 26 | 27 | 30 | 28 |
| Completed | 17 | 16 | 21 | 27 | 27 | 25 |
| Not completed | 2 | 1 | 5 | 0 | 3 | 3 |
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.
| Participants | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Culture negative | 5 | 5 | 17 | 14 | 15 | 13 |
| Culture positive | 14 | 11 | 9 | 12 | 12 | 13 |
Best corrected visual acuity will be measured at baseline for both eyes using the standard ETDRS chart light box at the 4- and 1-meter test distances. In the case that the patient reads less than 10 letters at 4 meters, move the patient or the chart to a distance of 1 meter from the patient.
| logMar | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Best Spectacle-corrected Visual Acuity | 0.82 (0.62 to 1.4) | 1.32 (0.43 to 1.75) | 0.43 (0.1 to 0.72) | 1 (0.3 to 1.8) | 0.48 (0.2 to 1.7) | 0.8 (0.5 to 1.24) |
Study clinician will measure infiltrate or scar size using a standardized protocol with the slit lamp biomicroscope. The geometric mean of the scar size will be measured by recording the horizontal and vertical diameter.
| mm | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Scar Size | 3.5 (2.7 to 4.0) | 3.0 (2.24 to 4.0) | 3.0 (2.5 to 3.5) | 3.9 (2.6 to 4.5) | 3.5 (2.7 to 4.5) | 3.1 (2.8 to 5.0) |
Adverse events include glaucoma, endophthalmitis, medication reaction, perforation including treatment by therapeutic penetrating keratoplasty.
| participants | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Perforation | 1 | 0 | 2 | 1 | 4 | 3 |
| Therapeutic penetrating keratoplasty | 3 | 1 | 5 | 5 | 5 | 3 |
| Endophthalmitis | 0 | 0 | 0 | 0 | 1 | 0 |
| Median tarsorrhaphy | 0 | 0 | 0 | 0 | 0 | 1 |
Mobility subscale: As measured by the Indian Visual Function Questionnaire (IVFQ) which records quality of life on a scale of 0 to 100 with 100 representing the best quality of life.
| score on a scale | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Vision Related Quality of Life | — | — | 89.6 (71.9 to 100) | 91.7 (75 to 100) | 95.8 (72.9 to 100) | 89.6 (71.9 to 100) |
Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bacterial Ulcer Control | 0/19 (0%) | 4/19 (21.1%) | 0/19 (0%) |
| Bacterial Ulcer Cross-linking | 0/17 (0%) | 1/17 (5.9%) | 0/17 (0%) |
| Fungal Ulcer Control With Natamycin | 0/26 (0%) | 7/26 (26.9%) | 0/26 (0%) |
| Fungal Ulcer Cross-linking Plus Natamycin | 0/27 (0%) | 6/27 (22.2%) | 0/27 (0%) |
| Fungal Ulcer Control With Amphotericin | 0/30 (0%) | 10/30 (33.3%) | 0/30 (0%) |
| Fungal Ulcer Cross-linking Plus Amphotericin | 0/28 (0%) | 6/28 (21.4%) | 1/28 (3.6%) |
| Event | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Therapeutic penetrating keratoplastyEye disorders | 3/19 | 1/17 | 5/26 | 5/27 | 5/30 | 3/28 |
| PerforationEye disorders | 1/19 | 0/17 | 2/26 | 1/27 | 4/30 | 3/28 |
| EndophthalmitisEye disorders | 0/19 | 0/17 | 0/26 | 0/27 | 1/30 | 0/28 |
| Event | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin |
|---|---|---|---|---|---|---|
| Median tarsorrhaphyEye disorders | 0/19 | 0/17 | 0/26 | 0/27 | 0/30 | 1/28 |
| Age, Continuous(years) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| Median | 60 (54.5 to 65) | 59 (48 to 66) | 50 (36 to 55) | 55 (47 to 65) | 45 (40 to 58) | 56 (45 to 65) | 54.5 (45 to 64) |
| Sex: Female, Male(Participants) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| Female | 6 | 9 | 9 | 12 | 16 | 11 | 63 |
| Male | 13 | 8 | 17 | 15 | 14 | 17 | 84 |
| Race (NIH/OMB)(Participants) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 19 | 17 | 26 | 27 | 30 | 28 | 147 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| India | 19 | 17 | 26 | 27 | 30 | 28 | 147 |
| Occupation(Participants) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| Agriculture | 12 | 8 | 16 | 13 | 18 | 13 | 80 |
| Nonagriculture | 6 | 9 | 10 | 14 | 12 | 15 | 66 |
| NA | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Medication use at enrollment(Participants) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| Count of participants | 8 | 10 | 18 | 21 | 19 | 24 | 100 |
| Affected Eye(Participants) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| Left | 8 | 8 | 11 | 12 | 18 | 13 | 70 |
| Right | 11 | 9 | 15 | 15 | 12 | 15 | 77 |
| Visual acuity(LogMar) | Bacterial Ulcer Control | Bacterial Ulcer Cross-linking | Fungal Ulcer Control With Natamycin | Fungal Ulcer Cross-linking Plus Natamycin | Fungal Ulcer Control With Amphotericin | Fungal Ulcer Cross-linking Plus Amphotericin | Total |
|---|---|---|---|---|---|---|---|
| Mean | 1.7 (0.7 to 1.7) | 1.7 (0.9 to 1.8) | 1.05 (0.62 to 1.12) | 1.1 (0.6 to 1.7) | 1.05 (0.62 to 1.7) | 1.22 (0.91 to 1.7) | 1.1 (0.63 to 1.7) |
6 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Nov 2015 to primary completion in Jun 2018, 31 months.
Results were first posted in Aug 2024, 6 years 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
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