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Herpetic Eye Disease Study (HEDS) II

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00000139
Recruitment Status : Completed
First Posted : September 24, 1999
Last Update Posted : March 24, 2010
Information provided by:
National Eye Institute (NEI)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Keratitis, Herpetic Ocular Herpes Simplex Herpes Simplex Behavioral: Stress Drug: Acyclovir Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Study Start Date : October 1992

Resource links provided by the National Library of Medicine

Drug Information available for: Acyclovir

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Protocol-specific criteria are noted in the description above.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00000139

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United States, California
Francis I. Proctor Foundation, University of California, San Francisco
San Francisco, California, United States
United States, Georgia
Emory Eye Center
Atlanta, Georgia, United States
United States, Illinois
Eye Center, University of Illinois, Chicago
Chicago, Illinois, United States
United States, Louisiana
Louisiana State University Eye Center
New Orleans, Louisiana, United States
United States, New York
Department of Ophthalmology, The Mount Sinai Medical Center
New York, New York, United States
United States, Pennsylvania
Wills Eye Hospital, Cornea Clinic
Philadelphia, Pennsylvania, United States
United States, Texas
Cullen Eye Institute, Baylor College of Medicine
Houston, Texas, United States
United States, Wisconsin
The Eye Institute, Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Sponsors and Collaborators
National Eye Institute (NEI)
Additional Information:
Layout table for additonal information Identifier: NCT00000139    
Other Study ID Numbers: NEI-38
First Posted: September 24, 1999    Key Record Dates
Last Update Posted: March 24, 2010
Last Verified: September 2009
Keywords provided by National Eye Institute (NEI):
Herpes Simplex Stromal Keratitis
Additional relevant MeSH terms:
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Herpes Simplex
Keratitis, Herpetic
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Corneal Diseases
Eye Diseases
Eye Infections, Viral
Eye Infections
Antiviral Agents
Anti-Infective Agents