Therapeutic Exploratory Study of Comparing Natamycin and Voriconazole to Treat Fungal Corneal Ulcer

NCT00557362 | Completed Phase 1 Results

• 1 other identifier: H9332-31301-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

We evaluated whether voriconazole is a superior treatment to natamycin for filamentous fungal keratitis in a randomized, masked, controlled trial. This is a therapeutic exploratory study to investigate the safety and feasibility of conducting a larger study and to generate preliminary data.

Conditions

Fungal Keratitis

Keywords

Keratitis; Eye Infection, Fungal; Fungal Eye Infection; Ocular Infection, Fungal; Fungal Keratitis; Mycotic Infections, Ocular; Voriconazole; Natamycin

Outcome Measures

Primary Outcomes (1)

• Best Spectacle Corrected Visual Acuity (BSCVA) 3 Months After Enrollment, Adjusting for Enrollment BSCVA in a Multiple Linear Regression Model

  The primary efficacy endpoint was BSCVA at 3 months in the study eye, using a linear regression model with 3-month BSCVA measured in logMAR (logarithm of the Minimum Angle of Resolution) as the outcome variable and treatment arm (voriconazole vs natamycin) and enrollment logMAR BSCVA and corneal de-epithelialization (yes or no) as covariates.

  3 months from enrollment

Secondary Outcomes (4)

• Time to Resolution of Epithelial Defect

  3 months from enrollment

• Size of Infiltrate/Scar Post-treatment Was Analyzed in a Linear Regression Model Using Enrollment Infiltrate/Scar Size as a Covariate.

  3 months from enrollment

• Subgroup Analysis - Best Spectacle-corrected Visual Acuity Examined by Voriconazole and Natamycin Treatment Arms in Subgroups of Fungal Ulcers (Fusarium Spp and Aspergillus Spp).

  3 months from enrollment

• Best Hard Contact Lens-corrected Visual Acuity 3 Months After Enrollment in a Multiple Linear Regression Model With Enrollment Hard Contact Lens-corrected Visual Acuity as a Covariate

  3 months from enrollment

Study Arms (4)

1

ACTIVE COMPARATOR

Topical voriconazole with corneal de-epithelialization

Drug: Voriconazole; Procedure: Corneal de-epithelialization

2

ACTIVE COMPARATOR

Topical voriconazole without corneal de-epithelialization

Drug: Voriconazole

3

ACTIVE COMPARATOR

Topical natamycin with corneal de-epithelialization

Drug: Natamycin 5%; Procedure: Corneal de-epithelialization

4

ACTIVE COMPARATOR

Topical natamycin without corneal de-epithelialization

Drug: Natamycin 5%

Interventions

Natamycin 5% DRUG

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

3; 4

Voriconazole DRUG

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

1; 2

Corneal de-epithelialization PROCEDURE

Corneal de-epithelialization at 1 week and 2 weeks from enrollment to increase epithelial penetration of antifungal medications.

1; 3

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• That Man May See, Inc.: collaborator
• Aravind Eye Hospitals, India: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator

Study Sites (2)

Aravind Eye Hospital

Madurai, Tamil Nadu, India

Location

Aravind Eye Hospital

Pondicherry, Tamil Nadu, India

Location

Related Publications (1)

• Prajna NV, Mascarenhas J, Krishnan T, Reddy PR, Prajna L, Srinivasan M, Vaitilingam CM, Hong KC, Lee SM, McLeod SD, Zegans ME, Porco TC, Lietman TM, Acharya NR. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol. 2010 Jun;128(6):672-8. doi: 10.1001/archophthalmol.2010.102.

  PMID: 20547942 DERIVED

MeSH Terms

Conditions

Keratitis; Eye Infections, Fungal

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; Mycoses; Bacterial Infections and Mycoses; Infections; Eye Infections

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Tom M/ Lietman
• Organization: University of California San Francisco Proctor Foundation

tom.lietman@ucsf.edu

4155022662

Study Officials

• Thomas M Lietman, MD

  Proctor Foundation, University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Nisha Acharya, MD MS

  Proctor Foundation, University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• N V Prajna, MD

  Aravind Eye Hospital, India

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2007
• First Posted: November 14, 2007
• Study Start: November 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: August 7, 2018
• Results First Posted: December 19, 2013

Record last verified: 2018-07

Locations

IN (2)