The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole vs Placebo
Condition: Corneal Ulcer; Eye Infections, Fungal
MeSH terms: Corneal Ulcer; Eye Infections; Mycoses; Eye Infections, Fungal; Ulcer
Intervention: Voriconazole; Placebo
Intervention description: 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 for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing <40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.; 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.
Intervention MeSH terms: Voriconazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 240.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Fungal Infections; Eye Disease; Fungal Keratitis; Visual Acuity

Summary:

      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.
    

Eligibility 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)

          -  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