Therapeutic Exploratory Study of Comparing Natamycin and Voriconazole to Treat Fungal Corneal Ulcer (MUTT_TE)
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Purpose
We are planning to evaluate whether voriconazole is a superior treatment to natamycin for filamentous fungal keratitis in a randomized, masked, controlled trial. The study being proposed in this application is a therapeutic exploratory study to investigate the safety and feasibility of conducting a larger study and to generate preliminary data.
| Condition | Intervention | Phase |
|---|---|---|
|
Fungal Keratitis |
Drug: Natamycin 5% Drug: Voriconazole Procedure: Corneal de-epithelialization |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Mycotic Ulcer Treatment Trial Therapeutic Exploratory Study |
- Best spectacle corrected visual acuity (BSCVA) 3 months after enrollment, adjusting for enrollment BSCVA in a multiple linear regression model [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
- Time to resolution of epithelial defect [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
- Size of infiltrate/scar post-treatment, using enrollment infiltrate/scar size as a covariate [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
- Subgroup analysis - It will be determined if voriconazole or natamycin results in better clinical outcomes in subgroups of fungal ulcers (Fusarium spp and Aspergillus spp). [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
- Best hard contact lens-corrected visual acuity 3 months after enrollment [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
| Enrollment: | 120 |
| Study Start Date: | November 2007 |
| Study Completion Date: | August 2008 |
| Primary Completion Date: | August 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
Topical voriconazole with corneal de-epithelialization
|
Drug: Voriconazole
Voriconazole (VFEND® I.V., Pfizer, New York, NY) will be prepared as a 1% solution. One drop of medication should be given every one hour while awake for one week. For another 2 weeks, one drop of medication should be given every 2 hours while awake Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
|
Active Comparator: 2
Topical voriconazole without corneal de-epithelialization
|
Drug: Voriconazole
Voriconazole (VFEND® I.V., Pfizer, New York, NY) will be prepared as a 1% solution. One drop of medication should be given every one hour while awake for one week. For another 2 weeks, one drop of medication should be given every 2 hours while awake |
|
Active Comparator: 3
Topical natamycin with corneal de-epithelialization
|
Drug: Natamycin 5%
One drop of medication will be given every one hour while awake for one week. For another 2 weeks, one drop of medication should be given every 2 hours while awake
Procedure: Corneal de-epithelialization
Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.
|
|
Active Comparator: 4
Topical natamycin without corneal de-epithelialization
|
Drug: Natamycin 5%
One drop of medication will be given every one hour while awake for one week. For another 2 weeks, one drop of medication should be given every 2 hours while awake
|
Detailed Description:
Fungal ulcers tend to have very poor outcomes with the most common treatments, amphotericin B and natamycin. There has been only a single randomized trial of anti-fungal therapy for fungal ulcers and no new medications have been approved by the FDA since the 1960s. There are studies that indicate that the newer triazoles, such as voriconazole, are more effective in vitro against filamentous fungi such as Aspergillus spp., a common cause of fungal keratitis1-3. Despite a number of case reports and in vitro studies, there has been no systematic attempt to determine whether it is more or less effective clinically than natamycin, the only commercially available FDA-approved agent. There is little data available for physicians to make an informed, evidence-based decision on choice of antifungal.
We are planning to evaluate whether voriconazole is a superior treatment to natamycin for filamentous fungal keratitis in a randomized, masked, controlled trial. The study being proposed in this application is a therapeutic exploratory study to investigate the safety and feasibility of conducting the main study and to generate preliminary data.
Eligibility| Ages Eligible for Study: | 16 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Presence of a corneal ulcer at presentation
- Evidence of filamentous fungus on KOH (or Giemsa or any other stain) or culture
- The patient must be able to verbalize a basic understanding of the study after it is explained to the patient, as determined by physician examiner. This understanding must include a commitment to return for follow-up visits.
- Willingness to be treated as an in-patient or to be treated as an out-patient and come back every 48-72 hours to receive fresh medication for 3 weeks
- Appropriate consent
Exclusion Criteria:
- Overlying epithelial defect < 0.5 mm at its greatest width at presentation
- Impending perforation
- Evidence of bacteria on Gram stain at the time of enrollment
- Evidence of acanthamoeba by stain
- Evidence of herpetic keratitis by history or exam
- Corneal scar not easily distinguishable from current ulcer
- Age less than 16 years (before 16th birthday)
- Bilateral ulcers
- Previous penetrating keratoplasty in the affected eye
- Pregnancy (by history or urine test) or breast-feeding (by history)
- Acuity worse than 6/60 (20/200) in the fellow eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA 6/60 or better qualifies for enrollment)
- Known allergy to study medications (antifungal or preservative)
- No light perception in the affected eye
- Not willing to participate
Contacts and Locations| India | |
| Aravind Eye Hospital | |
| Madurai, Tamil Nadu, India | |
| Aravind Eye Hospital | |
| Pondicherry, Tamil Nadu, India | |
| Principal Investigator: | Thomas M Lietman, MD | Proctor Foundation, University of California, San Francisco |
| Principal Investigator: | Nisha Acharya, MD MS | Proctor Foundation, University of California, San Francisco |
| Study Director: | N V Prajna, MD | Aravind Eye Hospital, India |
More Information
No publications provided by University of California, San Francisco
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University of California, San Francisco |
| ClinicalTrials.gov Identifier: | NCT00557362 History of Changes |
| Other Study ID Numbers: | H9332-31301-01 |
| Study First Received: | November 9, 2007 |
| Last Updated: | December 5, 2012 |
| Health Authority: | United States: Institutional Review Board India: Indian Council of Medical Research |
Keywords provided by University of California, San Francisco:
|
Keratitis Eye Infection, Fungal Fungal Eye Infection Ocular Infection, Fungal |
Fungal Keratitis Mycotic Infections, Ocular Voriconazole Natamycin |
Additional relevant MeSH terms:
|
Keratitis Corneal Diseases Eye Diseases Natamycin Voriconazole Anti-Infective Agents, Local Anti-Infective Agents |
Therapeutic Uses Pharmacologic Actions Antifungal Agents Anti-Bacterial Agents 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013