Topical Cyclosporine for Vernal Keratoconjunctivitis (VKC) in Rwanda

Topical Cyclosporine in the Treatment of Vernal Keratoconjunctivitis in a Rwandan Eye Clinic; a Prospective Randomized Double-masked Clinical Trial

Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, external ocular inflammatory disease of unknown cause. It is a fairly common disease in hot, dry environments, representing as much as 3% of severe ophthalmic diseases and up to 33% of all eye pathology seen among young patients in eye clinics in Central Africa. Symptoms and signs can persist for years with an important visual morbidity and social impact. Corneal changes (e.g. corneal ulcers) can be sight threatening, occurring in up to 10% of VKC children. Topical steroid therapy remains the current standard treatment, but in developing countries its use often is chronic and not medically supervised, potentially leading to bacterial infections, steroid-induced glaucoma and cataract. Chromoglycate drops have less side effects but lack the power to control a flare-up. Topical cyclosporine has the potential to offer an efficient but safer alternative to steroid drops in the management of VKC in an African setting. Its safety and efficiency in the management of vernal keratoconjunctivitis have been described in several uncontrolled studies and double-blind, placebo-controlled trials, but those studies were relatively small and involved populations outside Africa with predominantly palpebral and mixed forms of VKC. Controversy still remains on the efficiency of cyclosporine in severe forms of allergic conjunctivitis like VKC. We therefore undertake a larger prospective randomized double-masked, standard treatment controlled clinical trial in Central Africa to compare the short-term efficiency of cyclosporine A (CsA) 2% eye drops, solved in olive oil vehicle, with that of steroid drops in predominantly limbal forms of VKC. During 4 weeks the participants will be randomised to either cyclosporine or dexamethasone as attack treatment for VKC. The 4 weeks thereafter all participants will receive chromoglycate drops as maintenance treatment. Additional objectives are to document any difference in rebound phenomenon while on chromoglycate during the maintenance phase between the 2 treatment groups and to evaluate safety and tolerance of the test medication.

Study Overview

• Status: Completed
• Conditions: Vernal Keratoconjunctivitis
• Intervention / Treatment: Drug: Cyclosporine A; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 4

Contacts and Locations

Study Locations

• Rwanda
  • Gitarama/Muhanga, Rwanda
    • Kabgayi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- at least 5 years of age

Exclusion Criteria:

• being pregnant
• suffering from any other infectious or inflammatory ocular pathology
• using topical/ systemic corticosteroids, antihistamines, non-steroidal anti-inflammatory drugs or immunosuppressives 2 weeks prior to the trial
• been treated with steroid injection 6 months prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporine A; Cyclosporine A (CsA) 2% eye drops	Drug: Cyclosporine A; Cyclosporine 2% eye drops
Active Comparator: Dexamethasone; Dexamethasone 0,1% eye drops	Drug: Dexamethasone; Dexamethasone 0,1% eye drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in score for symptoms and clinical signs between treatment arms	Differences in scores for symptoms and clinical signs individually and as a composite score between the treatment arms. Symptoms are itchiness, tearing, stinging, discharge and photophobia. Signs are subtarsal scarring, limbal cysts, pseudogerontoxon, pseudomembrane, corneal plaque, shield-ulcer, bulbar hyperaemia, limbal pigmentation, punctate keratitis, tarsal plate papillae, corneal astigmatism, limbal follicles, conjunctivalisation of the cornea and trantas dots.	After 4 weeks at the end of 4 weeks test medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Speed of symptom/sign reduction	To document any difference between the 2 treatment groups in speed of symptom/sign reduction during the attack treatment and in rebound phenomenon while on chromoglycate during the maintenance phase	At 2 weeks while on test medication and at 8 weeks at the end of a chromoglycate maintenance phase
Safety and tolerance of the test medication	To evaluate safety and tolerance of the test medication.	At 2 weeks while on test medication and at 8 weeks at the end of a chromoglycate maintenance phase

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Novartis; Funds for Research in Ophthalmology (FRO) of Belgium
• Investigators: Principal Investigator: Philippe Kesteleyn, MD, PhD, University Hospital, Ghent

Publications and helpful links

Helpful Links

• website University Hospital Ghent

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 28, 2010
• First Submitted That Met QC Criteria: September 28, 2010
• First Posted (Estimate): September 29, 2010

Study Record Updates

• Last Update Posted (Estimate): September 29, 2010
• Last Update Submitted That Met QC Criteria: September 28, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Hypersensitivity; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Conjunctivitis, Allergic; Keratoconjunctivitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Dexamethasone; Cyclosporine; Cyclosporins
• Other Study ID Numbers: UZ Ghent 003