Trial record 2 of 33 for:    Open Studies | "Eye Infections"

Mycotic Ulcer Treatment Trial II (MUTT II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of California, San Francisco
Sponsor:
Collaborators:
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
Lumbini Eye Institute, Nepal
Bharatpur Eye Hospital, Nepal
Information provided by (Responsible Party):
Thomas M. Lietman, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00997035
First received: October 14, 2009
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine if the addition of oral voriconazole to topical treatment regimens results in lower rates of perforation in severe fungal corneal ulcers.


Condition Intervention Phase
Corneal Ulcer
Eye Infections, Fungal
Drug: Voriconazole
Drug: Placebo
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:
  • Rate of perforation [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
    Comparison of rate of perforation between the treatment groups (topical voriconazole with oral voriconazole vs. topical voriconazole with oral placebo)


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

  • 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

  • Best spectacle-corrected logMAR visual acuity [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    Best spectacle-corrected logMAR visual acuity 3 months after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear

  • 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 ]
  • Number of adverse events [ Time Frame: At the time of 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 ]

Estimated Enrollment: 240
Study Start Date: May 2010
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Oral Voriconazole Drug: Voriconazole

1% voriconazole (topical) 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.

5% natamycin (topical), 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.

400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment.

Placebo Comparator: Placebo Drug: Placebo

1% voriconazole (topical) 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.

5% natamycin (topical), 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.

Two tablets BID PO on study day one, then one tablet BID PO until 3 weeks from 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 of oral voriconazole in severe ulcers reduces the rate of perforations. 240 fungal corneal ulcers with baseline visual acuity worse than 6/120 presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive oral voriconazole plus topical voriconazole and topical natamycin, or oral placebo plus topical voriconazole and topical natamycin. The primary outcome is the rate of perforation over the three month follow-up period.

  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 worse than 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:

  • 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)
  • Weight less than 40 kg
  • Known liver disease, including hepatitis or cirrhosis (Child-Pugh A-C)
  • 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 better than 6/120 (20/400) in the study eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA can be used for enrollment)
  • Currently on rifampin, rifabutin, ritonavir, long acting barbiturates, phenytoin, carbamazepine, or other drugs known to interact with voriconazole
  • 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: NCT00997035

Contacts
Contact: Nisha Acharya, MD, MS 415-476-8131 nisha.acharya@ucsf.edu

Locations
United States, California
Proctor Foundation, UCSF Recruiting
San Francisco, California, United States, 94143
Contact: Kieran O'Brien, MPH    415-514-2163    kieran.obrien@ucsf.edu   
Principal Investigator: Tom Lietman, MD         
Principal Investigator: Nisha Acharya, MD, MS         
India
Aravind Eye Hospital Suspended
Coimbatore, Tamil Nadu, India
Aravind Eye Hospitals Suspended
Madurai, Tamil Nadu, India
Aravind Eye Hospital Suspended
Pondicherry, Tamil Nadu, India
Aravind Eye Hospital Suspended
Tirunelveli, Tamil Nadu, India
Nepal
Bharatpur Eye Hospital Recruiting
Bharatpur, Chitwan, Nepal
Contact: Kamal B Khadka, MD    0097-56-520333    beh@nec.com.np   
Principal Investigator: Kamal B Khadka, MD         
Lumbini Eye Institute Recruiting
Bhairahawa, Lumbini, Nepal
Contact: Kavita Dhakwha, MD    00977-71-520265, 523827    drkavitadh@gmail.com   
Principal Investigator: Kavita Dhakwha, MD         
Sponsors and Collaborators
University of California, San Francisco
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
Lumbini Eye Institute, Nepal
Bharatpur Eye Hospital, Nepal
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

Responsible Party: Thomas M. Lietman, Professor in Residence, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00997035     History of Changes
Other Study ID Numbers: H9332-33965-02_2, U10-EY018573-01A1
Study First Received: October 14, 2009
Last Updated: June 19, 2014
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:
Eye Infections
Eye Infections, Fungal
Corneal Ulcer
Mycoses
Ulcer
Infection
Keratitis
Corneal Diseases
Eye Diseases
Pathologic Processes
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014