Mycotic Ulcer Treatment Trial I

NCT00996736 | Completed Phase 3 Results DMC

• 2 other identifiers: H9332-33965-02U10EY018573-01A1
• Study Type: interventional
• Target: 323
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of this study is to determine if natamycin or voriconazole results in better visual outcomes in fungal corneal ulcers, especially visual acuity.

Conditions

Corneal Ulcer; Eye Infections, Fungal

Keywords

Fungal Infections; Eye Disease; Fungal Keratitis; Visual Acuity

Outcome Measures

Primary Outcomes (1)

• Best Spectacle-corrected logMAR Visual Acuity

  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).

  3 months from enrollment

Secondary Outcomes (6)

• Best Spectacle-corrected logMAR Visual Acuity

  3 weeks after enrollment

• Hard Contact Lens-corrected Visual Acuity Measured in logMAR

  3 months after enrollment

• Size of Infiltrate/Scar

  3 weeks and 3 months after enrollment

• Time to Resolution of Epithelial Defect

  From enrollment to the time of resolution of epithelial defect

• Minimum Inhibitory Concentration of Isolates

  3 months after enrollment

Study Arms (2)

Topical Natamycin

ACTIVE COMPARATOR

Drug: Natamycin

Topical Voriconazole

EXPERIMENTAL

Drug: Voriconazole

Interventions

Natamycin DRUG

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.

Topical Natamycin

Voriconazole DRUG

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.

Topical Voriconazole

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Aravind Eye Hospitals, India: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• National Eye Institute (NEI): collaborator

Study Sites (3)

Proctor Foundation, UCSF

San Francisco, California, 94143, United States

Location

Aravind Eye Hospitals

Madurai, Tamil Nadu, India

Location

Aravind Eye Hospital

Pondicherry, Tamil Nadu, India

Location

Related Publications (9)

• Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, Raghavan A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Porco TC, Acharya NR, Lietman TM; Mycotic Ulcer Treatment Trial Group. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol. 2013 Apr;131(4):422-9. doi: 10.1001/jamaophthalmol.2013.1497.

  PMID: 23710492 BACKGROUND

• Prajna NV, Lalitha P, Krishnan T, Rajaraman R, Radnakrishnan N, Srinivasan M, Devi L, Das M, Liu Z, Zegans ME, Acharya NR, Porco TC, Lietman TM, Rose-Nussbaumer J. Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India: A Post Hoc Analysis of 3 Randomized Clinical Trials. JAMA Ophthalmol. 2022 Feb 1;140(2):179-184. doi: 10.1001/jamaophthalmol.2021.5765.

  PMID: 35024776 DERIVED

• Prajna NV, Krishnan T, Rajaraman R, Patel S, Shah R, Srinivasan M, Das M, Ray KJ, Oldenburg CE, McLeod SD, Zegans ME, Acharya NR, Lietman TM, Rose-Nussbaumer J; Mycotic Ulcer Treatment Trial Group. Predictors of Corneal Perforation or Need for Therapeutic Keratoplasty in Severe Fungal Keratitis: A Secondary Analysis of the Mycotic Ulcer Treatment Trial II. JAMA Ophthalmol. 2017 Sep 1;135(9):987-991. doi: 10.1001/jamaophthalmol.2017.2914.

  PMID: 28817744 DERIVED

• Prajna NV, Krishnan T, Rajaraman R, Patel S, Shah R, Srinivasan M, Devi L, Das M, Ray KJ, O'Brien KS, Oldenburg CE, McLeod SD, Zegans ME, Acharya NR, Lietman TM, Rose-Nussbaumer J; Mycotic Ulcer Treatment Trial Group. Adjunctive Oral Voriconazole Treatment of Fusarium Keratitis: A Secondary Analysis From the Mycotic Ulcer Treatment Trial II. JAMA Ophthalmol. 2017 Jun 1;135(6):520-525. doi: 10.1001/jamaophthalmol.2017.0616.

  PMID: 28426856 DERIVED

• Prajna NV, Krishnan T, Rajaraman R, Patel S, Srinivasan M, Das M, Ray KJ, O'Brien KS, Oldenburg CE, McLeod SD, Zegans ME, Porco TC, Acharya NR, Lietman TM, Rose-Nussbaumer J; Mycotic Ulcer Treatment Trial II Group. Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial. JAMA Ophthalmol. 2016 Dec 1;134(12):1365-1372. doi: 10.1001/jamaophthalmol.2016.4096.

  PMID: 27787540 DERIVED

• Prajna NV, Lalitha P, Rajaraman R, Krishnan T, Raghavan A, Srinivasan M, O'Brien KS, Zegans M, McLeod SD, Acharya NR, Keenan JD, Lietman TM, Rose-Nussbaumer J; Mycotic Ulcer Treatment Trial Group. Changing Azole Resistance: A Secondary Analysis of the MUTT I Randomized Clinical Trial. JAMA Ophthalmol. 2016 Jun 1;134(6):693-6. doi: 10.1001/jamaophthalmol.2016.0530.

  PMID: 27054515 DERIVED

• Rose-Nussbaumer J, Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Srinivasan M, Raghavan A, Oldenburg CE, O'Brien KS, Ray KJ, Porco TC, McLeod SD, Acharya NR, Keenan JD, Lietman TM; Mycotic Ulcer Treatment Trial Group. Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole. Br J Ophthalmol. 2016 Jul;100(7):929-932. doi: 10.1136/bjophthalmol-2015-306828. Epub 2015 Nov 3.

  PMID: 26531051 DERIVED

• Rose-Nussbaumer J, Prajna NV, Krishnan KT, Mascarenhas J, Rajaraman R, Srinivasan M, Raghavan A, Oldenburg CE, O'Brien KS, Ray KJ, McLeod SD, Porco TC, Lietman TM, Acharya NR, Keenan JD; Mycotic Ulcer Treatment Trial I Group. Vision-Related Quality-of-Life Outcomes in the Mycotic Ulcer Treatment Trial I: A Randomized Clinical Trial. JAMA Ophthalmol. 2015 Jun;133(6):642-6. doi: 10.1001/jamaophthalmol.2015.0319.

  PMID: 25764482 DERIVED

• Sun CQ, Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Srinivasan M, Raghavan A, O'Brien KS, Ray KJ, McLeod SD, Porco TC, Acharya NR, Lietman TM. Expert prior elicitation and Bayesian analysis of the Mycotic Ulcer Treatment Trial I. Invest Ophthalmol Vis Sci. 2013 Jun 14;54(6):4167-73. doi: 10.1167/iovs.13-11716.

  PMID: 23702779 DERIVED

MeSH Terms

Conditions

Corneal Ulcer; Eye Infections, Fungal; Mycoses; Eye Diseases

Interventions

Natamycin; Voriconazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Thomas Lietman
• Organization: F.I. Proctor Foundation, University of Califonia, San Francisco

tom.lietman@ucsf.edu

415-502-2662

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: April 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: August 1, 2018
• Results First Posted: December 11, 2013

Record last verified: 2018-07

Locations

IN (2); US (1)