The Role of Adjuvant Corneal Crosslinking in the Management of Infective Keratitis

NCT06967376 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: RIO Egypt (approval number 109
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This was a prospective, single centre, randomised controlled study to evaluate the clinical effectiveness of corneal collagen crosslinking as an adjuvant to antimicrobial therapy.

Conditions

Infective Keratitis

Outcome Measures

Primary Outcomes (1)

• clinical response

  Ulcer dimensions will be studied on slit lamp and AS-OCT.

  At presentation; and then on day 7, day 14 and day 30 of commencing treatment

Study Arms (2)

Arm that take medical treatment only for infective keratitis

ACTIVE COMPARATOR

On presentation, all pre-existing treatment was stopped for 48 hours and corneal scrapes for direct smears and cultures using blood agar, chocolate agar, thioglycolate broth and sabouraud dextrose agar were done. Initial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/ml, fortified ceftazidime eye drops 50 mg/ml hourly, and the antifungal agent itraconazole 100 mg orally twice per day. This regimen was subject to change according to microbiology culture sensitivities and/or results.

Drug: Topical Antimicrobial/Antifungal Medications

Arm of patients take cross linking as an adjuvant treatment to medical treatment

ACTIVE COMPARATOR

Patients allocated to the PACK-CXL group were assessed and treated by PACK-CXL within 2 days of treatment initiation. Topical anaesthesia was achieved using 0.4% benoxinate hydrochloride drops. Epithelium was removed up to 9 mm diameter. Corneal thickness of the area to be treated was measured (without epithelium) aiming for a starting thickness of no less than 350μm. Corneas thicker than 500μm were dehydrated to reduce thickness by using 70% Glycerol drops applied topically at intervals of 2-3 seconds for a total of five minutes. A schematic representation of PACK-CXL protocol is provided in Figure 1. Iso-osmolar riboflavin drops were instilled topically on the cornea at regular intervals of 2 minutes for a total period of 30 minutes. Thickness was also re-measured every 5 min to ensure that it remained below 500µm during instillation of riboflavin. The cornea was illuminated using a UVX, UV-A 365 nm with an irradiance of 3 mW/cm2 for 30 minutes and a total dose of 5.4 J/cm2 during

Procedure: Corneal Collagen Cross-Linking Solutions

Interventions

Corneal Collagen Cross-Linking Solutions PROCEDURE

Topical anaesthesia was achieved using 0.4% benoxinate hydrochloride drops. Epithelium was removed up to 9 mm diameter. Corneal thickness of the area to be treated was measured (without epithelium) aiming for a starting thickness of no less than 350μm. Corneas thicker than 500μm were dehydrated to reduce thickness by using 70% Glycerol drops applied topically at intervals of 2-3 seconds for a total of five minutes. A schematic representation of PACK-CXL protocol is provided in Figure 1. Iso-osmolar riboflavin drops were instilled topically on the cornea at regular intervals of 2 minutes for a total period of 30 minutes. Thickness was also re-measured every 5 min to ensure that it remained below 500µm during instillation of riboflavin. The cornea was illuminated using a UVX, UV-A 365 nm with an irradiance of 3 mW/cm2 for 30 minutes and a total dose of 5.4 J/cm2 during which riboflavin was instilled every 2 min and corneal pachymetry performed every 5 min. PACK-CXL was performed in a 9

Arm of patients take cross linking as an adjuvant treatment to medical treatment

Topical Antimicrobial/Antifungal Medications DRUG

Initial antimicrobial therapy for both groups consisted of fortified vancomycin eye drops 50 mg/ml, fortified ceftazidime eye drops 50 mg/ml hourly, and the antifungal agent itraconazole 100 mg orally twice per day. This regimen was subject to change according to microbiology culture sensitivities and/or results.

Arm that take medical treatment only for infective keratitis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with infectious keratitis

You may not qualify if:

• Infective keratitis \< 1mm from limbus
• Corneal thickness \< 350μm
• Previous herpetic eye disease
• Expectant and nursing women

Sponsors & Collaborators

• Research Institute of Ophthalmology, Egypt: lead

Study Sites (2)

Research Institute of Ophthalmology

Giza, Giza Governorate, Egypt

Location

Research Institute of Ophthalmology

Giza, Egypt

Location

MeSH Terms

Interventions

Anti-Infective Agents

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Methods Study Design: A prospective, single centre, randomised controlled study of forty eyes of forty patients was conducted. The study was approved by local institutional review board (Approval number 109) and adhered to the Declaration of Helsinki. All patients provided informed consent before enrolling and participating in the study. Selection: All patients presenting with infective keratitis were explained about the study and informed consent was sought (CONSORT Diagram). Fifty-three patients were screened against the exclusion criteria and 13 were excluded. The remaining total of 40 patients were allocated equally to two groups (A and B) by process of simple randomisation. Group A patients were to be offered standard targeted anti-microbial therapy whilst group B were offered CXL in addition to the standard targeted anti-microbial therapy.

Study Record Dates

• First Submitted: November 2, 2024
• First Posted: May 13, 2025
• Study Start: May 21, 2018
• Primary Completion: November 11, 2021
• Study Completion: February 3, 2022
• Last Updated: May 13, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

EG (2)