Combination Treatment of 5% Natamycin and 1% Voriconazole in Fungal Keratitis

NCT03230058 | Unknown Phase 2 DMC

• 1 other identifier: GMRV_NATA01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

OBJECTIVE To evaluate the efficacy and safety of the concurrent treatment of 5% Natamycin and 1% Voriconazole in patients affected by fungal keratitis METHODS AND MATERIALS STUDY POPULATION Patients with smear and or culture proven fungal keratitis presenting to our Instituts, were eligible for enrollment. STUDY DESIGN Prospective double masked randomized clinical trial.

Conditions

Infection, Fungal

Outcome Measures

Primary Outcomes (1)

• Success or failure

  Primary End point: Complete success: Complete resolution of the infiltrate with formation of a scar on medical treatment alone Partial success: Complete resolution of the infiltrate on medical treatment and use of cyanoacrylate glue and bandage contact lens Failure: Worsening of the ulcer necessitating therapeutic penetrating keratoplasty or evisceration

  8 weeks

Secondary Outcomes (1)

• Best-corrected visual acuity

  8 weeks

Study Arms (2)

group 1

EXPERIMENTAL

Once the patient is randomized to either of the 2 groups using computer-generated randomization blocks, the hospital pharmacist would provide the appropriate medications. The treating ophthalmologist, microbiologist and patients will be masked to the drug by using similar vials. The experimental group (Group 1) will receive 1% voriconazole eye drop (Aurolab, Madurai, India) + 5% Natamycin ophthalmic suspension eye drop hourly (USP 5% Natamet, M.J. Pharmaceuticals, Mumbai, India). The subjects will be hospitalized for at least 4 days with medications given by the ward nurse. Patients will be followed up every week after being discharged until complete resolution is noted.

Drug: Group 1 Natamycin 5% Suspension + voriconazole 1% eye drops; Group 2 Natamycin 5% Suspension + Vehicle eye drops

group 2

PLACEBO COMPARATOR

Once the patient is randomized to either of the 2 groups using computer-generated randomization blocks, the hospital pharmacist would provide the appropriate medications. The treating ophthalmologist, microbiologist and patients will be masked to the drug by using similar vials. The placebo group (Group 2) will receive Vehicle eye drops + 5% Natamycin ophthalmic suspension every hour (USP 5% Natamet, M.J. Pharmaceuticals, Mumbai, India). The subjects will be hospitalized for at least 4 days with medications given by the ward nurse. Patients will be followed up every week after being discharged until complete resolution is noted.

Drug: Group 1 Natamycin 5% Suspension + voriconazole 1% eye drops; Group 2 Natamycin 5% Suspension + Vehicle eye drops

Interventions

Group 1 Natamycin 5% Suspension + voriconazole 1% eye drops; Group 2 Natamycin 5% Suspension + Vehicle eye drops DRUG

instillation of drops

group 1; group 2

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects \> 18 yrs of age Willing to give appropriate informed consent Presence of corneal ulcer measuring \> 2mm in vertical and horizontal dimensions at presentation (epithelial defect and signs of stromal inflammation) Microbiologic evidence of fungus on smear and or culture media Willing to return for all the follow up visits

You may not qualify if:

• Patients not willing to give consent Patients unable to cooperate for the procedure Patient with impending, or actual perforation or bilateral corneal ulcer or scleral involvement History of previous ocular surgery Evidence of bacterial, parasitic or viral infection or co-infection Previous corneal scar Known allergy to the study medication (drug or preservative) Pregnant or nursing females Immunocompromised patients

Sponsors & Collaborators

• L.V. Prasad Eye Institute: lead

Study Sites (1)

GMRV Campus LV Prasad Eye Insitute

Visakhapatnam, Andhra Pradesh, India

RECRUITING

Related Publications (3)

• Sharma S, Das S, Virdi A, Fernandes M, Sahu SK, Kumar Koday N, Ali MH, Garg P, Motukupally SR. Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial. Br J Ophthalmol. 2015 Sep;99(9):1190-5. doi: 10.1136/bjophthalmol-2014-306485. Epub 2015 Mar 4.

  PMID: 25740805 BACKGROUND

• Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol. 2004 Aug;15(4):321-7. doi: 10.1097/00055735-200408000-00008.

  PMID: 15232472 RESULT

• Di Zazzo A, Surico PL, Parmar UPS, Tarini S, De Luca A, Madduri B, Mohan N, Fernandes M. Efficacy of natamycin monotherapy versus combination therapy with voriconazole for fungal keratitis: a randomised clinical trial. Br J Ophthalmol. 2025 Dec 9:bjo-2025-328695. doi: 10.1136/bjo-2025-328695. Online ahead of print.

  PMID: 41365527 DERIVED

MeSH Terms

Conditions

Mycoses

Interventions

Suspensions; Voriconazole; Ophthalmic Solutions

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Solutions; Solutions; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• merle fernandes, MS

  LVPEI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Di Zazzo, MD

CONTACT

antoniodizazzo@gmail.com

merle ferndnades, MS

CONTACT

merle@lvpei.org

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: MS

Study Record Dates

• First Submitted: July 23, 2017
• First Posted: July 26, 2017
• Study Start: January 1, 2017
• Primary Completion: March 1, 2018
• Study Completion: September 30, 2018
• Last Updated: July 26, 2017

Record last verified: 2017-07

Locations

IN (1)