NCT00997035

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started May 2010

Longer than P75 for phase_3

Geographic Reach
3 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 14, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 16, 2009

Completed
7 months until next milestone

Study Start

First participant enrolled

May 1, 2010

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2016

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 14, 2017

Completed
Last Updated

February 26, 2019

Status Verified

February 1, 2019

Enrollment Period

5.7 years

First QC Date

October 14, 2009

Results QC Date

June 9, 2016

Last Update Submit

February 4, 2019

Conditions

Corneal UlcerEye Infections, Fungal

Keywords

Fungal InfectionsEye DiseaseFungal KeratitisVisual Acuity

Outcome Measures

Primary Outcomes (1)

  • Incidence of Perforation or Therapeutic Penetrating Keratoplasty

    Hazard ratio of perforation or therapeutic penetrating keratoplasty (TPK) comparing voriconazole to placebo

    3 months from enrollment

Secondary Outcomes (9)

  • Best Spectacle-corrected logMAR Visual Acuity

    3 months after enrollment

  • Best Spectacle-corrected logMAR Visual Acuity at 3-weeks

    3 weeks after enrollment

  • Size of Infiltrate/Scar - 3 Months

    3 months after enrollment

  • Size of Infiltrate/Scar

    3 weeks after enrollment

  • Hazard Ratio for Re-epithelialization

    Up to 21 days

  • +4 more secondary outcomes

Study Arms (2)

Oral Voriconazole

ACTIVE COMPARATOR
Drug: Voriconazole

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

VoriconazoleDRUG

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.

Oral Voriconazole
PlaceboDRUG

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.

Placebo

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Proctor Foundation, UCSF

San Francisco, California, 94143, United States

Location

Aravind Eye Hospital

Coimbatore, Tamil Nadu, India

Location

Aravind Eye Hospitals

Madurai, Tamil Nadu, India

Location

Aravind Eye Hospital

Pondicherry, Tamil Nadu, India

Location

Aravind Eye Hospital

Tirunelveli, Tamil Nadu, India

Location

Bharatpur Eye Hospital

Bharatpur, Chitwan, Nepal

Location

Lumbini Eye Institute

Siddharthanagar, Lumbini, Nepal

Location

Related Publications (1)

  • Zegans ME, Kamath MM, Jones JT, Bao R, Ross BS, Gutierrez-Perez C, Adams EM, Lightfoot JD, Poimenidou G, Pavuluri C, Prajna V, Cramer RA, Fuller KK. Propranolol is efficacious against Aspergillus and Fusarium corneal isolates in vitro and in a murine model of Aspergillus keratitis. Antimicrob Agents Chemother. 2025 Jun 4;69(6):e0166424. doi: 10.1128/aac.01664-24. Epub 2025 May 15.

    PMID: 40372030DERIVED

MeSH Terms

Conditions

Corneal UlcerEye Infections, FungalMycosesEye Diseases

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Eye InfectionsInfectionsKeratitisCorneal DiseasesBacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Kathryn Ray
Organization
University of California, San Francisco
kathryn.ray@ucsf.edu
415-514-3227

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor in Residence

Study Record Dates

First Submitted

October 14, 2009

First Posted

October 16, 2009

Study Start

May 1, 2010

Primary Completion

January 1, 2016

Study Completion

March 1, 2016

Last Updated

February 26, 2019

Results First Posted

June 14, 2017

Record last verified: 2019-02

Locations

US(1)NE(2)IN(4)