Mycotic Ulcer Treatment Trial I (MUTT I)
Eye Infections, Fungal
|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|
- Best Spectacle-corrected logMAR Visual Acuity [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]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).
- Best Spectacle-corrected logMAR Visual Acuity [ Time Frame: 3 weeks after enrollment ] [ Designated as safety issue: No ]Best spectacle-corrected logMAR (logarithm of the Minimum Angle of Resolution) visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear regression model
- 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 (logarithm of the Minimum Angle of Resolution) 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: From enrollment to the time of resolution of epithelial defect ] [ Designated as safety issue: No ]Time in days from enrollment to resolution of epithelial defect. For those subjects with more than 21 days to resolution, 21 days was used.
- Minimum Inhibitory Concentration of Isolates [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]Minimum inhibitory concentration (50th percentile) of fungal isolates to natamycin and voriconazole
- Microbiological Cure at 6 Days [ Time Frame: 7 days after enrollment ] [ Designated as safety issue: No ]Microbiological cure defined as no fungal growth on culture at 6 (+/-1) days from enrollment
|Study Start Date:||April 2010|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
|Active Comparator: Topical Natamycin||
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.
|Experimental: Topical Voriconazole||
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.
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 natamycin or voriconazole results in better outcomes for fungal corneal ulcers. 368 fungal corneal ulcers with baseline visual acuity between 6/12 (20/40, logMAR 0.3) and 6/120 (20/400, logMAR 1.3) presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive either topical natamycin or topical voriconazole. The primary outcome is best spectacle-corrected logMAR visual acuity three months after enrollment, using best spectacle-corrected enrollment visual acuity as a co-variate.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00996736
|United States, California|
|Proctor Foundation, UCSF|
|San Francisco, California, United States, 94143|
|Aravind Eye Hospitals|
|Madurai, Tamil Nadu, India|
|Aravind Eye Hospital|
|Pondicherry, Tamil Nadu, India|
|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|