Herpetic Eye Disease Study (HEDS) I



Sponsors


Source

National Eye Institute (NEI)

Brief Summary

To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal
keratitis in conjunction with topical trifluridine.

To evaluate the efficacy of oral acyclovir in treating herpes simplex stromal keratitis in
patients receiving concomitant topical corticosteroids and trifluridine.

To evaluate the efficacy of oral acyclovir in treating herpes simplex iridocyclitis in
conjunction with treatment with topical corticosteroids and trifluridine.

Detailed Description

Herpes simplex keratitis is a leading cause of corneal opacification in the United States,
other industrialized countries, and developing nations throughout the world. An estimated
450,000 people in the United States can develop recurrent episodes of the disease and about
46,000 episodes of HSV eye infection every year. Herpetic eye disease is the most common
infectious cause of corneal blindness in this country.

Despite the availability of antiviral agents that are effective in treating herpes simplex
epithelial keratitis, inflammation in the corneal connective tissue and iris that can lead to
corneal scarring and visual impairment develops in many patients. Prior to the HEDS-I trials,
the role of topical corticosteroids in the management of HSV stromal keratitis was uncertain;
some animal and human studies suggested there was a benefit to treatment whereas others
suggested harm. The value of adding an oral antiviral agent to treatment with topical
corticosteroids and topical antivirals also was unknown.

The HEDS-I trials were developed to assess the efficacy of topical corticosteroids and oral
acyclovir in treating HSV stromal keratitis and iridocyclitis.

HEDS-I consisted of three randomized, placebo-controlled trials. The organizational structure
consisted of a data coordinating center and eight clinical centers.

All patients received the topical antiviral trifluridine as prophylaxis against recurrences
of HSV epithelial ulceration. Patients were evaluated weekly for 10 weeks, every other week
through week 16, and again at 6 months. The primary outcome was the time to development of
preset criteria for treatment failure during the 16-week period of examination.
Protocol-specific descriptions of the three trials follow.

Herpes Stromal Keratitis, Not on Steroid Trial (HEDS-SKN): Patients with active HSV stromal
keratitis who had not used a topical corticosteroid in the preceding 10 days were randomized
to treatment with topical prednisolone phosphate drops or topical placebo drops. A treatment
schedule, starting with 8 drops a day of 1 percent prednisolone phosphate for 7 days, was
progressively decreased over 10 weeks in such a way that patients received 1 drop per day of
1/8 percent prednisolone for the last 3 weeks of treatment. Placebo drops were given by the
same schedule.

Herpes Stromal Keratitis, on Steroid Treatment (HEDS-SKS): Patients with active HSV stromal
keratitis who already were being treated with a topical corticosteroid were randomized either
to oral treatment with 200 mg acyclovir capsules (400 mg five times daily) for 10 weeks or to
the identical dose of placebo capsules. Patients also received topical prednisolone phosphate
in the dosage schedule described above for the SKN trial.

Herpes Simplex Virus Iridocyclitis, Receiving Topical Steroids (HEDS-IRT): Patients with
active HSV iridocyclitis were randomized either to oral treatment with 200 mg acyclovir
capsules (400 mg five times daily) for 10 weeks or to the identical dose of placebo capsules.
Patients also received topical prednisolone phosphate in the dosage schedule described above
for the SKN trial.

Overall Status

Unknown status

Start Date

1989-05-01

Completion Date

N/A

Primary Completion Date

N/A

Phase

Phase 3

Study Type

Interventional


Conditions


Intervention

Intervention Type

Drug

Intervention Name



Intervention Type

Drug

Intervention Name




Eligibility

Criteria

Eligibility criteria common to the three protocols included age 12 years or older, no
active HSV epithelial keratitis, no prior keratoplasty of the involved eye, and not
pregnant. Protocol-specific criteria are noted in the description above.

Gender

All

Minimum Age

12 Years

Maximum Age

N/A

Healthy Volunteers

No


Verification Date

2009-09-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Keyword


Has Expanded Access

No

Condition Browse


Intervention Browse

Mesh Term

Prednisolone acetate

Methylprednisolone acetate

Prednisolone

Methylprednisolone

Methylprednisolone Hemisuccinate

Prednisolone phosphate

Prednisolone hemisuccinate

Acyclovir



Firstreceived Results Date

N/A

Reference

Citation

Dawson CR. The herpetic Eye Disease Study. Arch Ophthalmol. 1990 Feb;108(2):191-2.

PMID

2405826


Citation

Dawson CR; Jones DB; Kaufman HE; Barron BA; Hauck WW; Wilhelmus KR; The Herpetic Eye Disease Study: Strategies of design and data analysis [Abstract]., Invest Ophthalmol Vis Sci 1990;31:553


Citation

Dawson CR, Jones DB, Kaufman HE, Barron BA, Hauck WW, Wilhelmus KR. Design and organization of the herpetic eye disease study (HEDS). Curr Eye Res. 1991;10 Suppl:105-10.

PMID

1864086


Citation

Dawson CR; Jones DB; Wilhelmus KR; Kaufman HE; Barron BA; Hauck WW; Evaluation of corneal inflammatory disease: The Herpetic Eye Disease Study (HEDS) [Abstract]., Invest Ophthalmol Vis Sci 1991;32:1221


Citation

Dawson CR; Hauck WW; Jones DB; Kaufman HE; Gee L; Barron BA; Wilhelmus KR; The Herpetic Eye Disease Study (HEDS). Clinical characteristics of randomized patients with herpetic stromal keratitis and iridocyclitis prior to initiating treatment [Abstract]., Invest Ophthalmol Vis 1992;33:1134


Citation

Barron BA, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, Wilhelmus KR, Kaufman HE, Sugar J, Hyndiuk RA, et al. Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1871-82.

PMID

7997323


Citation

Wilhelmus KR, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, Barron BA, Kaufman HE, Sugar J, Hyndiuk RA, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1883-95; discussion 1895-6.

PMID

7997324


Citation

A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 1996 Sep;114(9):1065-72.

PMID

8790090


Citation

Wilhelmus KR, Dawson CR, Barron BA, Bacchetti P, Gee L, Jones DB, Kaufman HE, Sugar J, Hyndiuk RA, Laibson PR, Stulting RD, Asbell PA. Risk factors for herpes simplex virus epithelial keratitis recurring during treatment of stromal keratitis or iridocyclitis. Herpetic Eye Disease Study Group. Br J Ophthalmol. 1996 Nov;80(11):969-72.

PMID

8976723



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Primary Purpose

Treatment


Study First Submitted

September 23, 1999

Study First Submitted Qc

September 23, 1999

Study First Posted

September 24, 1999

Last Update Submitted

September 16, 2009

Last Update Submitted Qc

September 16, 2009

Last Update Posted

September 17, 2009

Last Known Status

Active, not recruiting


ClinicalTrials.gov processed this data on August 24, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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