Herpetic Eye Disease Study (HEDS) II

NCT ID: NCT00000139

Last Updated: 2010-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

1992-10-31

Brief Summary

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To determine whether early treatment (with oral acyclovir) of herpes simplex virus (HSV) ulcerations of the corneal epithelium prevents progression to the blinding complications of stromal keratitis and iridocyclitis.

To determine the efficacy of low-dose oral acyclovir in preventing recurrent HSV eye infection in patients with previous episodes of herpetic eye disease.

To determine the role of external factors (such as ultraviolet light or corneal trauma) and behavioral factors (such as life stress) on the induction of ocular recurrences of HSV eye infections and disease.

Detailed Description

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Infection of the eye by herpes simplex virus (HSV) is a leading cause of corneal blindness in the United States and other countries. The infection can lead to corneal scarring and neovascularization, permanent endothelial dysfunction and corneal edema, secondary glaucoma, and cataract. Despite the availability of topical antiviral agents that are highly active against HSV keratitis, there is still no known effective method for reducing the frequency of recurrence or severity of stromal keratitis and iridocyclitis. In addition, the prognosis is poor for recovery of good vision following penetrating keratoplasty for actively inflamed or highly vascularized herpetic corneas.

On the basis of both animal and human studies, the antiviral agent acyclovir may both treat and prevent recurrence of HSV disease. However, no consensus yet exists on the use of acyclovir in the management and prevention of herpetic eye disease.

HEDS-II consists of two randomized, placebo-controlled trials that are assessing the role of oral acyclovir in the management of herpetic eye disease and one epidemiologic study that is investigating risk factors, including stress, for the development of ocular recurrences of the disease. The organizational structure consists of a national coordinating center, eight regional coordinating clinical centers, and approximately 60 clinical sites. The clinical sites where patients are enrolled and followed include both university-based and community-based practices.

Herpes Simplex Virus Epithelial Keratitis Trial: HEDS-EKT evaluated the benefit of oral acyclovir given during treatment of an acute HSV keratitis (dendritic or geographic keratitis) in preventing the occurrence of later blinding complications. Patients entered the trial within 7 days of onset. All patients received standard treatment with a topical antiviral and were randomized to receive either oral acyclovir (400 mg five times a day for 21 days) or a placebo. Patients had eight visits within a 12-month followup period. The primary outcome was the time to the first occurrence of stromal keratitis or iridocyclitis in the study eye (eye with epithelial keratitis at time of study entry). The HEDS-EKT recruitment goal was 502 patients.

Acyclovir Prevention Trial: HEDS-APT evaluated the benefit of long-term acyclovir treatment in patients with a recent history of HSV eye disease but no current active disease. To be eligible, a patient must have experienced any kind of ocular herpes simplex infection (blepharitis, conjunctivitis, keratitis, or iridocyclitis) in the preceding year. The infection must have been inactive and untreated for at least the previous 30 days. Patients were randomized to receive either oral acyclovir (400 mg twice a day) or placebo for 1 year. Five followup visits occurred during the 1-year treatment period and an additional three followup visits during the 6-month post-treatment period. Episodes of recurrent HSV eye disease during the trial were treated with topical corticosteroids and antivirals as indicated, but patients continued to receive the oral acyclovir or placebo for the entire 365-day period. The primary outcome was the time to the first recurrence of any type of HSV eye disease in either eye. The recruitment goal was 696 patients.

Ocular HSV Recurrence Factor Study: HEDS-RFS is evaluating the effect of psychological, environmental, and biological factors on recurrences of herpetic eye disease. Patients recruited into the HEDS-APT trial are eligible to participate in HEDS-RFS if they are 18 years or older. At entry, all subjects fill out a questionnaire to estimate the negative affectivity trait measure. Subjects also fill out a short questionnaire every week for 52 weeks to track acute and chronic stressors (e.g., illnesses, injuries, menstrual periods, sun exposure, emotional and financial stresses). The investigators ensure patient privacy by the patient's mailing of the weekly logs directly to the HEDS National Coordinating Center.

Conditions

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Keratitis, Herpetic Ocular Herpes Simplex Herpes Simplex

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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Stress

Intervention Type BEHAVIORAL

Acyclovir

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Eye Institute (NEI)

NIH

Sponsor Role lead

Locations

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Francis I. Proctor Foundation, University of California, San Francisco

San Francisco, California, United States

Site Status

Emory Eye Center

Atlanta, Georgia, United States

Site Status

Eye Center, University of Illinois, Chicago

Chicago, Illinois, United States

Site Status

Louisiana State University Eye Center

New Orleans, Louisiana, United States

Site Status

Department of Ophthalmology, The Mount Sinai Medical Center

New York, New York, United States

Site Status

Wills Eye Hospital, Cornea Clinic

Philadelphia, Pennsylvania, United States

Site Status

Cullen Eye Institute, Baylor College of Medicine

Houston, Texas, United States

Site Status

The Eye Institute, Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Dawson CR, Beck R, Wilhelmus KR, Cohen EJ. Herpetic eye disease study. You can help. Arch Ophthalmol. 1996 Jan;114(1):89-90. doi: 10.1001/archopht.1996.01100130085015. No abstract available.

Reference Type BACKGROUND
PMID: 8540857 (View on PubMed)

A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 1997 Jun;115(6):703-12. doi: 10.1001/archopht.1997.01100150705001.

Reference Type BACKGROUND
PMID: 9194719 (View on PubMed)

Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300-6. doi: 10.1056/NEJM199807303390503.

Reference Type BACKGROUND
PMID: 9696640 (View on PubMed)

Other Identifiers

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NEI-38

Identifier Type: -

Identifier Source: org_study_id

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