Keratitis, HerpeticPhase 3NCT00000138
Herpetic Eye Disease Study (HEDS) I
A Phase 3 study testing Prednisolone Phosphate and Acyclovir in people with Keratitis, Herpetic and Ocular Herpes Simplex, run by National Eye Institute (NEI).
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Keratitis, Herpetic, Ocular Herpes Simplex
- What is being tested?
- Prednisolone Phosphate and Acyclovir
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- May 1989to not given
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
About this study
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.
Read the 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.
- Conditions
- Keratitis, Herpetic, Ocular Herpes Simplex
- Being tested
- Prednisolone Phosphate, Acyclovir
- Keywords
- Herpes Simplex Stromal Keratitis
- Medical subject headings
- Keratitis, Herpetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prednisolone PhosphateDrug
AcyclovirDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 1999 (estimated)
- Study startMay 1989
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Keratitis, HerpeticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000138
- Sponsor's protocol ID
- NEI-37
- Status last verified
- Sep 2009
- First submitted
- 23 Sep 1999
- Last updated
- 17 Sep 2009
- Results posted
- No
Publications
Dawson CR. The herpetic Eye Disease Study. Arch Ophthalmol. 1990 Feb;108(2):191-2. doi: 10.1001/archopht.1990.01070040043027. No abstract available.
PubMed 2405826Dawson 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
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. doi: 10.3109/02713689109020365.
PubMed 1864086Dawson 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
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
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. doi: 10.1016/s0161-6420(13)31155-5.
PubMed 7997323Wilhelmus 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. doi: 10.1016/s0161-6420(94)31087-6.
PubMed 7997324A 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. doi: 10.1001/archopht.1996.01100140267002.
PubMed 8790090Wilhelmus 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. doi: 10.1136/bjo.80.11.969.
PubMed 8976723Wilhelmus KR, Mitchell BM, Jones DB; Herpetic Eye Disease Study Group. Photographic monitoring of herpes simplex virus keratitis during anti-inflammatory treatment. Arch Ophthalmol. 2011 Feb;129(2):252-3. doi: 10.1001/archophthalmol.2010.366. No abstract available.
PubMed 21320979
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Herpetic Eye Disease Study (HEDS) I
- ClinicalTrials.gov ID
- NCT00000138
- Acronym / sponsor ID
- NEI-37
- Conditions
- Keratitis, Herpetic, Ocular Herpes Simplex
- Keywords
- Herpes Simplex Stromal Keratitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- May 1989
- First posted
- 24 Sep 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prednisolone Phosphate | Drug | – |
| Acyclovir | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2009.
- Background: PubMed 2405826Dawson CR. The herpetic Eye Disease Study. Arch Ophthalmol. 1990 Feb;108(2):191-2. doi: 10.1001/archopht.1990.01070040043027. No abstract available.
- BackgroundDawson 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
- Background: PubMed 1864086Dawson 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. doi: 10.3109/02713689109020365.
- BackgroundDawson 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
- BackgroundDawson 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
- Background: PubMed 7997323Barron 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. doi: 10.1016/s0161-6420(13)31155-5.
- Background: PubMed 7997324Wilhelmus 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. doi: 10.1016/s0161-6420(94)31087-6.
- Background: PubMed 8790090A 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. doi: 10.1001/archopht.1996.01100140267002.
- Background: PubMed 8976723Wilhelmus 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. doi: 10.1136/bjo.80.11.969.
- Derived from this study: PubMed 21320979Wilhelmus KR, Mitchell BM, Jones DB; Herpetic Eye Disease Study Group. Photographic monitoring of herpes simplex virus keratitis during anti-inflammatory treatment. Arch Ophthalmol. 2011 Feb;129(2):252-3. doi: 10.1001/archophthalmol.2010.366. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Prednisolone Phosphate and Acyclovir in people with Keratitis, Herpetic and Ocular Herpes Simplex, run by National Eye Institute (NEI).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000138, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2009.