Mycotic Ulcer Treatment Trial I (MUTT I)

July 6, 2018 updated by: Thomas M. Lietman, University of California, San Francisco

Mycotic Ulcer Treatment Trial

The purpose of this study is to determine if natamycin or voriconazole results in better visual outcomes in fungal corneal ulcers, especially visual acuity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

323

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Tamil Nadu
      • Madurai, Tamil Nadu, India
        • Aravind Eye Hospitals
      • Pondicherry, Tamil Nadu, India
        • Aravind Eye Hospital
  • United States
    • California
      • San Francisco, California, United States, 94143
        • Proctor Foundation, UCSF

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Spectacle-corrected logMAR Visual Acuity
Time Frame: 3 months from enrollment
The primary analysis is best spectacle-corrected logMAR (logarithm of the Minimum Angle or Resolution) 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).
3 months from enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Spectacle-corrected logMAR Visual Acuity
Time Frame: 3 weeks after enrollment
Best spectacle-corrected logMAR (logarithm of the Minimum Angle of Resolution) visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear regression model
3 weeks after enrollment
Hard Contact Lens-corrected Visual Acuity Measured in logMAR
Time Frame: 3 months after enrollment
Hard contact lens-corrected visual acuity measured in logMAR (logarithm of the Minimum Angle of Resolution) 3 months after enrollment
3 months after enrollment
Size of Infiltrate/Scar
Time Frame: 3 weeks and 3 months after enrollment
Size of infiltrate/scar at 3 weeks and 3 months after enrollment, using enrollment infiltrate scar/size as a covariate
3 weeks and 3 months after enrollment
Time to Resolution of Epithelial Defect
Time Frame: From enrollment to the time of resolution of epithelial defect
Time in days from enrollment to resolution of epithelial defect. For those subjects with more than 21 days to resolution, 21 days was used.
From enrollment to the time of resolution of epithelial defect
Minimum Inhibitory Concentration of Isolates
Time Frame: 3 months after enrollment
Minimum inhibitory concentration (50th percentile) of fungal isolates to natamycin and voriconazole
3 months after enrollment
Microbiological Cure at 6 Days
Time Frame: 7 days after enrollment
Microbiological cure defined as no fungal growth on culture at 6 (+/-1) days from enrollment
7 days after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Eye Institute (NEI)
Dartmouth-Hitchcock Medical Center
Aravind Eye Hospitals, India

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

July 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

October 14, 2009

First Submitted That Met QC Criteria

October 15, 2009

First Posted (Estimate)

October 16, 2009

Study Record Updates

Last Update Posted (Actual)

August 1, 2018

Last Update Submitted That Met QC Criteria

July 6, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H9332-33965-02
  • U10EY018573-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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