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Swiss PACK-CXL Multicenter Trial for the Treatment of Infectious Keratitis

2016-03-25 06:53:24 | BioPortfolio

Summary

To assess the safety and efficacy of PACK-CXL (photoactivated chromophore for infectious keratitis cross-linking) as a firstline treatment for infectious corneal infiltrates and early corneal ulcers, and compare it to the current standard of care, antimicrobial therapy.

Description

Research relevant to our study In 2008, a new concept was taken from transfusion medicine and transferred to ophthalmology: the reduction of pathogen load in platelet concentrates is achieved by treatment of concentrates with riboflavin (Vit B2 as a chromophore and UV-A light). In analogy, a research group in Zurich, Switzerland, of whom the PI of the current application was part of, showed that this application could be also applied in human corneal infection.

The proof-of-principle study included 5 corneas that were therapy-resistant to any conventional type of treatment. In all five cases, the corneal infection calmed down within days to weeks and all eyes could be saved. In the same year, the effect of riboflavin/UV-A irradiation was shown on several bacteria and fungi in vitro, with a killing rate of almost 98% within 30 minutes for the most common strains responsible for bacterial keratitis like Methicillin resistant Staph aureus and Pseudomonas aeruginosa. A case series and a clinical phase 1 study performed by Makdoumi et al showed the beneficial effect of PACK-CXL (photoactivated chromophore for the treatment of infectious keratitis-corneal collagen crosslinking) in 15 eyes of 15 patients with early onset corneal ulcers. Here, PACK-CXL was even used as the primary therapy, whereas controls received maximal conventional therapy (medication). Again, PACKCXL alone was beneficial in the outcome in all eyes investigated. Between 2010 and 2013, the PI of this application was PI of a randomized prospective clinical trial examining the effect of adjuvant PACK-CXL therapy in advanced corneal ulcers with associated melting. Even in these far advanced cases with impending perforation, the additional effect of PACK-CXL was significant, with a drop in the ulcer-related complication rate from 23% (controls) to 0%. A number of smaller reports and case series have shown the effect of PACK-CXL on other bacterial, and also fungal infections.

Study's overall goal The overall goal of this study is to demonstrate that PACK-CXL is not just a valuable adjuvant therapy, but rather a primary treatment modality used in the beginnings of a corneal ulcer, at the stage of an infiltrate or beginning ulcer. Current standard of care would then rather play a secondary, supporting role than a primary one. Importance of the study on global eye health. The economic and socioeconomic costs related to corneal ulcers and their medical treatment are immense. For example, treatment of a fungal ulcer might cost several thousands of US Dollars. PACK-CXL, in contrast, does not require (expensive) medication, but rather Vitamin B2 solution and a light source. Also, in vitro and in vivo data show that PACK-CXL is highly efficient in antibiotic-resistant infection with MRSA. Furthermore, PACK-CXL is based on CXL, a well-established technique used in other corneal diseases. The study PI of the current application was part of the team of researchers and clinicians that developed the original CXL technology.

Rationale A Riboflavin solution is administered to the cornea in the form of eye drops. After an administration of 25 minutes (one drop every 2 minutes), the cornea is then irradiated with UV-A light at a wavelength of 365nm and a total energy of 5.4 J/cm2 (use 30 min @ 3 mW/cm2, 10 min @ 9 mw/cm2, or 5 min @ 18mW/cm2). These settings are identical with the standard CXL settings routinely used in clinical practice worldwide. The safety of these settings has been verified in multiple experimental and clinical studies over the past 15 years.

Our hypothesis PACK-CXL might be highly beneficial in the treatment of corneal infection, as an adjuvant therapy in advanced cases, and also a primary mode of treatment in early cases. In this study, the patients are to be examined after treatment with closer control range than is customary at this condition.

The treatment is in clinical use and has a strong theoretical support. Patients will not run an increased risk of injury compared with conventional treatments, as the checks are more frequent than normal and thus, the slightest sign of progress can be detected early. We do not expect any increased suffering from the treatment or inferior healing compared to the usual treatment. The study offers the possibility of a new tool to treat a difficult condition, where the need of culturing decreases and reduces use of antibiotics.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Keratitis; Infectious Disease (Manifestation)

Intervention

PACK-CXL, Cefazolin in combination with either tobramycin or gentamicin, Cycloplegic agents (cyclopentolate 1% eye drops), Fluoroquinolones (Besifloxacin ; ciprofloxacin ; gatifloxacin ; levofloxacin ; moxifloxacin ; ofloxacin ), Corticosteroids (predniso

Location

University of Geneva
Geneva
GE
Switzerland
1211

Status

Recruiting

Source

University Hospital, Geneva

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-03-25T06:53:24-0400

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