Mycotic Ulcer Treatment Trial I (MUTT I)

This study has been completed.
Sponsor:
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: October 18, 2013
Last verified: October 2013
  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 (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).


Secondary Outcome Measures:
  • Best Spectacle-corrected logMAR Visual Acuity [ Time Frame: 3 weeks after enrollment ] [ Designated as safety issue: No ]
    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

  • 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 (logarithm of the Minimum Angle of Resolution) 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: From enrollment to the time of resolution of epithelial defect ] [ Designated as safety issue: No ]
    Time in days from enrollment to resolution of epithelial defect. For those subjects with more than 21 days to resolution, 21 days was used.

  • Minimum Inhibitory Concentration of Isolates [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    Minimum inhibitory concentration (50th percentile) of fungal isolates to natamycin and voriconazole

  • Microbiological Cure at 6 Days [ Time Frame: 7 days after enrollment ] [ Designated as safety issue: No ]
    Microbiological cure defined as no fungal growth on culture at 6 (+/-1) days from enrollment


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided by University of California, San Francisco

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: July 26, 2013
Last Updated: October 18, 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
Infection
Mycoses
Ulcer
Corneal Diseases
Eye Diseases
Keratitis
Pathologic Processes
Natamycin
Voriconazole
14-alpha Demethylase Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Local
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014