Mycotic Ulcer Treatment Trial I (MUTT I)
This study has been completed.
Sponsor:
University of California, San Francisco
Collaborators:
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
Information provided by (Responsible Party):
Thomas M. Lietman, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00996736
First received: October 14, 2009
Last updated: February 25, 2013
Last verified: February 2013
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Purpose
The purpose of this study is to determine if natamycin or voriconazole results in better visual outcomes in fungal corneal ulcers, especially visual acuity.
| Condition | Intervention | Phase |
|---|---|---|
|
Corneal Ulcer Eye Infections, Fungal |
Drug: Natamycin Drug: Voriconazole |
Phase 3 |
| 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 |
Resource links provided by NLM:
Further study details as provided by University of California, San Francisco:
Primary Outcome Measures:
- Best spectacle-corrected logMAR visual acuity [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]The primary analysis is best spectacle-corrected logMAR visual acuity, correcting for enrollment BSCVA and treatment arm in a multiple linear regression model. The pre-specified non-inferiority margin is less than 1.5 lines logMAR acuity. (Adjusted three-month visual acuity confidence bounds for the difference between the voriconazole and natamycin groups which meet or exceed 0.15 logMAR units would not permit noninferiority to be declared.) Note that this design also allows declaration of superiority (2-sided alpha of 0.05, corrected for an interim analysis).
Secondary Outcome Measures:
- Best spectacle-corrected logMAR visual acuity [ Time Frame: 3 weeks after enrollment ] [ Designated as safety issue: No ]Best spectacle-corrected logMAR visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear regression model
- Best spectacle-corrected logMAR visual acuity only in Indian sites [ Time Frame: 3 weeks and 3 months after enrollment ] [ Designated as safety issue: No ]Best spectacle-corrected logMAR visual acuity only in Indian sites, 3 weeks and 3 months after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear regression model
- Hard contact-lens corrected visual acuity measured in logMAR [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]Hard contact-lens corrected visual acuity measured in logMAR 3 months after enrollment
- Size of infiltrate/scar [ Time Frame: 3 weeks and 3 months after enrollment ] [ Designated as safety issue: No ]Size of infiltrate/scar at 3 weeks and 3 months after enrollment, using enrollment infiltrate scar/size as a covariate
- Time to resolution of epithelial defect [ Time Frame: At the time of resolution of epithelial defect ] [ Designated as safety issue: No ]Time to resolution of epithelial defect
- Number of perforations and other adverse events [ Time Frame: At the time of perforation/adverse event ] [ Designated as safety issue: No ]
- Minimum inhibitory concentration of isolates [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
- Microbiological cure at 7 days [ Time Frame: 7 days after enrollment ] [ Designated as safety issue: No ]
| Enrollment: | 323 |
| Study Start Date: | April 2010 |
| Study Completion Date: | July 2012 |
| Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: Topical Natamycin |
Drug: Natamycin
5% natamycin plus 0.02% preservative, one drop to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until 3 weeks after enrollment.
|
| Experimental: Topical Voriconazole |
Drug: Voriconazole
1% voriconazole plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.
|
Detailed Description:
Fungal corneal ulcers tend to have very poor outcomes with commonly used treatments. There has only been a single randomized trial of anti-fungal therapy for mycotic keratitis, and no new ocular anti-fungal medications have been approved by the FDA since the 1960s. The triazole voriconazole has recently become the treatment of choice for systemic fungal infections such as pulmonary aspergillosis. The use of topical ophthalmic preparations of voriconazole has been described in numerous case reports, however there has been no systematic attempt to determine whether it is more or less clinically effective than natamycin. Additionally, there have been many case reports of the use of oral voriconazole in the treatment of fungal corneal ulcers, however there has been no systematic attempt to determine if it improves outcomes in severe ulcers.
This study is a randomized, double-masked, placebo-controlled trial to determine if the use natamycin or voriconazole results in better outcomes for fungal corneal ulcers. 368 fungal corneal ulcers with baseline visual acuity between 6/12 (20/40, logMAR 0.3) and 6/120 (20/400, logMAR 1.3) presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive either topical natamycin or topical voriconazole. The primary outcome is best spectacle-corrected logMAR visual acuity three months after enrollment, using best spectacle-corrected enrollment visual acuity as a co-variate.
Eligibility| Ages Eligible for Study: | 16 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Presence of a corneal ulcer at presentation
- Evidence of filamentous fungus on smear (KOH wet mount, Giemsa, or Gram stain)
- Visual acuity between 6/12 (20/40, logMAR 0.3) and 6/120 (20/400, logMAR 1.3)
- 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 inpatient or to be treated as an outpatient and return every 3 days +/- 1 day until re-epithelialization and every week to receive fresh medication for 3 weeks
- Appropriate consent
Exclusion Criteria:
- 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 (2/200) in the fellow eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA 6/60 or better qualifies for enrollment)
- Acuity worse than 6/120 (20/400) or better than 6/12 (20/40) in the study eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA can be used for enrollment)
- Known allergy to study medications (antifungal or preservative)
- No light perception in the affected eye
- Not willing to participate
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00996736
Locations
| United States, California | |
| Proctor Foundation, UCSF | |
| San Francisco, California, United States, 94143 | |
| India | |
| Aravind Eye Hospitals | |
| Madurai, Tamil Nadu, India | |
| Aravind Eye Hospital | |
| Pondicherry, Tamil Nadu, India | |
Sponsors and Collaborators
University of California, San Francisco
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
Investigators
| Principal Investigator: | NV Prajna, DNB, FRC Ophth | Aravind Eye Hospitals |
| Principal Investigator: | Nisha Acharya, MD, MS | Proctor Foundation, UCSF |
| Principal Investigator: | Tom Lietman, MD | Proctor Foundation, UCSF |
More Information
Publications:
| Responsible Party: | Thomas M. Lietman, Professor in Residence, University of California, San Francisco |
| ClinicalTrials.gov Identifier: | NCT00996736 History of Changes |
| Other Study ID Numbers: | H9332-33965-02, U10-EY018573-01A1 |
| Study First Received: | October 14, 2009 |
| Last Updated: | February 25, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of California, San Francisco:
|
Fungal Infections Eye Disease Fungal Keratitis Visual Acuity |
Additional relevant MeSH terms:
|
Corneal Ulcer Eye Infections Eye Infections, Fungal Mycoses Ulcer Infection Keratitis Corneal Diseases Eye Diseases Pathologic Processes 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