Herpes Zoster OphthalmicusPhase 4ZEDSNCT03134196
Zoster Eye Disease Study
A Phase 4 study testing Masked Oral Valacyclovir in people with Herpes Zoster Ophthalmicus, run by NYU Langone Health at 78 sites in 2 countries.
Trial summary
This is a multi-center, randomized, double-masked, placebo-controlled clinical trial of suppressive valacyclovir for one year in immunocompetent study participants with an episode of dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to Herpes Zoster Ophthalmicus (HZO) in the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Herpes Zoster Ophthalmicus
- What is being tested?
- Masked Oral Valacyclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 527 participants
- Where
- 78 sitesin 2 countries
- Study dates
- 23 Aug 2017to 22 Jul 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
PARTICIPANT INCLUSION CRITERIA
To be eligible for study participation, an individual must meet all of the following criteria:
- Ability to understand, and willingness and ability to read and sign, the informed consent form.
- Ability to understand and follow instructions and study procedures.
- Willingness to comply with all study procedures and be available for the duration of the study.
- Ability to take oral medication, and are willing to adhere to study medication regimen.
- Age 18 years or older.
- Diagnosed with HZO in one eye based on both of these criteria:
- History of characteristic unilateral, usually vesicular, HZO rash in the dermatomal distribution of cranial nerve V1 or V2.
- Medical record documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to HZO within the preceding year. This episode of active anterior segment ocular disease may be due to HZO of recent onset (within the preceding 6 months); or chronic HZO (with onset six or more months ago); may be new, worsening, or recurrent disease after a period of inactivity; and may occur after medication was reduced.
- Study participants with chronic HZO must be on a stable treatment regimen and off antivirals for at least 30 days before enrollment. Study participants with chronic HZO who do not meet this criterion may be rescreened, if they are able to meet this criterion within 3 months after the study visit. This is not a requirement for study participants with recent onset HZO, who may be enrolled at any time, preferably after completing recommended acute antiviral treatment, if prescribed, is completed. They can be on variable dose of steroids, and only need to be off oral and topical antivirals by the enrollment visit.
- For females with reproductive potential, willingness to use highly effective contraception (e.g., hormonal contraception, barrier contraception, intrauterine device, or abstinence).
PARTICIPANT EXCLUSION CRITERIA
An individual who meets any of the following criteria will be excluded from participation in this study:
- History of immunocompromised status as defined by current CDC contraindications for the vaccine against zoster (44).
- Study participants who are diagnosed with leukemia, lymphomas or other malignant neoplasms affecting bone marrow or lymphatic system, unless leukemia in remission and off chemotherapy for at least 3 months.
- Study participants who are diagnosed with Acquired Immune Deficiency Syndrome (AIDS) or presents with other clinical manifestations of Human Immunodeficiency virus (HIV) including CD4 count of ≤ 200 cells/ml.
- Study participants on immunosuppressive therapy including:
- High-dose corticosteroids (greater than equivalent of prednisone 20 mg/day within 1 month) ii. Chemotherapy, other than low dose used for treatment of immune-mediated diseases within 3 months iii. Study participants receiving recombinant human immune mediators and immune modulators, especially antitumor necrosis agents, within 1 month prior to enrollment d. Study participants with unspecified cellular immunodeficiency. e. Study participants with history of hematopoietic stem cell transplantation.
- Medical history of a systemic disease and thought likely to meet one of the exclusion criteria listed in exclusion criterion #1 during the 18-month study period.
- Renal insufficiency:
- Requires dialysis or has history of renal transplant or
- eGFR less than 45, determined within 3 months days preceding enrollment.
- Allergy or adverse reaction to valacyclovir or acyclovir.
- History of vaccination against zoster within one month prior to enrollment. Study participants who meet this exclusion criterion may be may be screened and enrollment delayed until eligible within 3 months. If the study participant receives the Herpes Zoster Subunit vaccine (Recombinant Zoster Vaccine (RZV), Shingrix), rescreening should take place one month after the second required dose of the vaccine.
- Keratorefractive surgery, other than limbal relaxing incisions or astigmatic keratotomies at the time of cataract surgery, within 5 years of enrollment, or keratoplasty of the involved eye with zoster.
- On systemic antivirals with activity against herpes within the past 30 days, including acyclovir, valacyclovir, or famciclovir, for any reason except for treatment of recent onset HZO, including investigational drug trial.
- History of another condition that may require treatment with one of these three antivirals listed above in exclusion criterion #7, during the course of the study; study participants who require chronic suppressive antiviral treatment with these medications will be excluded.
- Sexually active women who are pregnant, nursing, or in their reproductive years who do not agree to use contraception during the 1-year treatment period.
- Incarceration
- Any condition or circumstance that in the opinion of the study investigator, would place the study participant in increased risk or affect his/her full compliance or completion of the study.
- Participation in a clinical study testing a drug, biologic, device or other intervention within the last 30 days from enrollment visit. Study participants who meet this criterion may be rescreened.
Trial locations and contacts
78 sites in 2 countries.
78 sites in 2 countries
United States71 sites
Albany Stratton VA Medical Center
Albany, New York, 12208
University of Michigan
Ann Arbor, Michigan, 48105
Eye Consultants of Atlanta, PC
Atlanta, Georgia, 30339
University of Colorado
Aurora, Colorado, 80045
Vantage Eye Care Center, LLC
Bala-Cynwyd, Pennsylvania, 19004
University of Maryland
Baltimore, Maryland, 21201
The Krieger Eye Institute
Baltimore, Maryland, 21215
Wilmer Eye Institute John Hopkins
Bethesda, Maryland, 20817
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
Finger Lakes Ophthalmology /The Eye Care Center
Canandaigua, New York, 14424
University of Illinois
Chicago, Illinois, 60612
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
Case Western Reserve University
Cleveland, Indiana, 44106
Case Western Reserve University
Cleveland, Ohio, 44106
Cornea Associates of Texas
Dallas, Texas, 75231
University of Texas Southwestern
Dallas, Texas, 75390
Geisinger Eye Clinic
Danville, Pennsylvania, 17822
Delray Eye Associates, PA
Delray Beach, Florida, 33484
Duke University
Durham, North Carolina, 27710
Stony Brook Ophthalmology
East Setauket, New York, 11733
Cornea Consultants of Texas
Fort Worth, Texas, 76107
University of Florida
Gainesville, Florida, 32610
NorthShore University Health System
Glenview, Illinois, 60026
Northwest Eye Clinic
Golden Valley, Minnesota, 55427
Verdier Eye Center
Grand Rapids, Michigan, 49546
Northwell Health
Great Neck, New York, 11021
Alkek Eye Center - Baylor College of Medicine
Houston, Texas, 77030
Indiana University - Glick Eye Institute
Indianapolis, Indiana, 46202
Florida Eye Specialists
Jacksonville, Florida, 33204
Scripps Clinic
La Jolla, California, 92037
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Kentucky
Lexington, Kentucky, 40509
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Colorado Cornea Consultants P.C.
Littleton, Colorado, 80120
Loma Linda University Eye Institute
Loma Linda, California, 92354
Jules Stein Eye Clinic - UCLA
Los Angeles, California, 90095
University of Wisconsin - Madison
Madison, Wisconsin, 53705
University of Tennessee - Hamilton Eye Institute
Memphis, Tennessee, 38163
University of Miami - Bascom Palmer Eye Institute
Miami, Florida, 33136
Jennifer Burdick
Minnetonka, Minnesota, 55305
EyeCare MD of NJ
Morristown, New Jersey, 07960
Cornea and Cataract Consultants of Nashville
Nashville, Tennessee, 37203
Vanderbilt Eye Institute
Nashville, Tennessee, 37232
LSU Health Science Center
New Orleans, Louisiana, 70112
New York Eye and Ear Infirmary
New York, New York, 10003
NYU Langone Health
New York, New York, 10016
Weill Cornell Ophthalmology
New York, New York, 10021
Crossroads Eye Physician
Owings Mills, Maryland, 21117
Byers Eye Institute at Stanford University
Palo Alto, California, 94303
Lahey Medical Center
Peabody, Massachusetts, 01960
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Corneal Associates at Wills Eye Hospital
Philadelphia, Pennsylvania, 19107
Devers Eye Institute
Portland, Oregon, 97210
Casey Eye Institute - Oregon Health and Science University
Portland, Oregon, 97239
University of Kansas Medical Center
Prairie Village, Kansas, 66208
Virginia Eye Institute
Richmond, Virginia, 23226
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah - Moran Eye Center
Salt Lake City, Utah, 84132
R and R Eye Research, LLC
San Antonio, Texas, 78229
UCSF- Francis I. Proctor Foundation
San Francisco, California, 94131
Pacific Eye Surgeons, Inc.
San Luis Obispo, California, 93401
Mayo Clinic - Arizona
Scottsdale, Arizona, 85259
Virginia Mason Medical Center
Seattle, Washington, 98101
NY Eye Surgeons
Seattle, Washington, 98133
Shreveport Eye Clinic
Shreveport, Louisiana, 71106
Washington University Opthalmology
St Louis, Missouri, 63110
Medstar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Eye Health Services
Weymouth, Massachusetts, 02189
Canada7 sites
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
Kingston Health Sciences Centre-HDH Site and Queen's University
Kingston, Ontario, K7L 5G2
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X 3E4
The Research Institute of the McGill University Health Centre/McGill Academic Eye Centre
Montreal, Quebec, H3A 4S5
Prism Eye Institute
Oakville, Ontario, L6H 0J8
Clinique Axe Visuel
Sherbrooke, Quebec, J1H4C7
University of British Columbia/Vancouver General Hospital Eye Care Centre
Vancouver, British Columbia, V5Z 3N0
About this study
Official title: Long-term Suppressive Valacyclovir Treatment for Herpes Zoster Ophthalmicus
This is a multi-center, randomized, double-masked, placebo-controlled clinical trial of suppressive valacyclovir for one year in immunocompetent study participants with an episode of dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to Herpes Zoster Ophthalmicus (HZO) in the year prior to enrollment.
Read the detailed description
The objective of the Zoster Eye Disease Study (ZEDS) is to determine whether prolonged suppressive oral antiviral treatment with valacyclovir reduces complications of Herpes Zoster Ophthalmicus (HZO), thereby improving clinical outcomes in this common and potentially vision- and life-threatening disease. There are 1,000,000 new cases of Herpes Zoster (HZ) per year in the USA, with 10-20% being HZO.
Specific Aims
Primary Aim: The primary aim of this double-masked, placebo controlled multicenter randomized clinical trial will test the hypothesis that suppressive antiviral treatment for 12 months with oral valacyclovir 1000 mg daily reduces the rate of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or iritis compared to placebo, at 12 months as the primary endpoint, and at 18 months including 6 months of follow-up after treatment, as a secondary endpoint, in patients with HZO who have had an episode of one of these disease manifestations during the year prior to enrollment.
Secondary Aim: The second aim is to test the hypothesis that suppressive treatment for 12 months with oral valacyclovir 1000 mg daily reduces the severity and duration of postherpetic neuralgia (PHN), compared to placebo, at 12 months and at 18 months as secondary endpoints, in similar patients with HZO. PHN is a debilitating chronic pain syndrome that negatively impacts quality of life, especially in elderly patients.
The study will enroll immunocompetent patients age 18 years and older who have HZO diagnosed at variable times in the past, with these types of active anterior segment ocular segment disease within the past year. Eligible patients will be randomized in a 1:1 ratio to long-term suppressive treatment with oral valacyclovir 1000 mg daily or placebo for 12 months, plus usual ophthalmic care, and followed every 3 months for a total of 18 months, to determine outcomes of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or iritis and/or severity and duration of PHN during 12 months of treatment and for 6 months following treatment discontinuation. The results with regard to PHN may be applicable to HZ in other locations. If suppressive valacyclovir treatment is determined to be effective, the potentially devastating disease burden of HZO and HZ may be reduced for patients, as well as the annual costs to society, estimated in the USA to be one billion dollars.
- Conditions
- Herpes Zoster Ophthalmicus
- Being tested
- Masked Placebo, Masked Oral Valacyclovir
- Keywords
- Herpes Zoster Ophthalmicus, Zoster Eye Disease Study, Varicella Zoster Virus, Zoster, Shingles
- Medical subject headings
- Herpes Zoster Ophthalmicus, Chickenpox, Herpes Zoster
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Masked PlaceboDrug
Oral Placebo
Masked Oral ValacyclovirDrug
Also called Valtrex
Oral Valacyclovir 1000 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Encapsulated masked placebo Receives: Drug: Masked Placebo |
| Masked Oral Valacyclovir 1000 mg daily | Active comparator | Valacyclovir, 500 mg, oral pill, two 500mg pills daily Receives: Drug: Masked Oral Valacyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With the First Occurrence of New or Worsening Stromal Keratitis Without Ulceration (SK), Endothelial Keratitis (EK), Iritis (IR), Dendriform Epithelial Keratitis (DEK), or Stromal Keratitis With Ulceration (SKU)
The number of participants with the first confirmed endpoint (new or worsening SK, EK, IR, DEK or SKU associated with pre-specified definitions of these disease manifestations and associated treatment requirements within 12 months in study participants assigned to valacyclovir compared to placebo. Diagnostic criteria were defined using the classification for SK, EK, SKU, and DEK caused by Herpes Simplex Virus (HSV) and standardization of uveitis nomenclature (SUN) for IR. A substantial increase in topical steroid treatment, defined as starting, shifting from a lower to higher potency steroid, or doubling frequency of steroid at one visit (new) or gradually within 3 months (worsening) was required for SK, EK, IR, and SKU.
Measured: Month 12
Secondary outcomes (5)
Number of Participants With Persistent Treatment Benefit at 18 Months, 6 Months After Cessation of Treatment
A secondary endpoint, at 18 months, assessed whether the treatment effect persisted 6 months after treatment. Diagnostic criteria were defined using the classification for SK, EK, SKU, and DEK caused by HSV and standardization of uveitis nomenclature (SUN) for IR. A substantial increase in topical steroid treatment, defined as starting, shifting from a lower to higher potency steroid, or doubling frequency of steroid at one visit (new) or gradually within 3 months (worsening) was required for SK, EK, IR, and SKU.
Measured: Month 18 (6 months post treatment)
Number of Postherpetic Neuralgia (PHN) Episodes
PHN was defined by a Zoster Brief Pain Inventory (ZBPI) score of ≥ 3 (the level at which pain interferes with normal activities), persisting, occurring, or reoccurring 3 or more months after the onset of Herpes Zoster Ophthalmicus (HZO).
Measured: Month 12
Number of Postherpetic Neuralgia (PHN) Episodes
PHN was defined by a ZBPI score of ≥ 3 (the level at which pain interferes with normal activities), persisting, occurring, or reoccurring 3 or more months after the onset of HZO
Measured: Month 18 (6 months post treatment)
Average Duration of Postherpetic Neuralgia (PHN) Pain
The duration of pain after zoster is obtained at every visit when they reported pain. Outcome measure was obtained using the Zoster Brief Pain Inventory (ZBPI) score of worst pain in last 24 hours of 3/10 (the level at which pain interferes with normal activities) or more occurring 3 or more months after HZO onset was used to determine the prevalence, severity and duration of PHN.
Measured: Month 24 (12 months post-treatment)
Average Duration of Postherpetic Neuralgia (PHN) Pain
The duration of pain after zoster is obtained at every visit when they reported pain. Outcome measure was obtained using the Zoster Brief Pain Inventory (ZBPI) score of worst pain in last 24 hours of 3/10 (the level at which pain interferes with normal activities) or more occurring 3 or more months after HZO onset was used to determine the prevalence, severity and duration of PHN.
Measured: Month 30 (18 months post treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2017
- Study start23 Aug 2017
- Primary completion31 Dec 2023
- Study completion22 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Herpes Zoster OphthalmicusStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 527 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Eye Institute (NEI), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Elisabeth Cohen, MD, Study chair, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03134196
- Sponsor's protocol ID
- 16-00463
- Other IDs
- 1U10EY026869
- Acronym
- ZEDS
- Status last verified
- Feb 2025
- First submitted
- 26 Apr 2017
- Last updated
- 7 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mian SI, Kim J, Troxel AB, Cohen EJ, Jeng BH; ZEDS Trial Research Group. Outcomes of Recombinant Zoster Vaccination in Herpes Zoster Ophthalmicus: A Secondary Analysis of the Zoster Eye Disease Study. Cornea. 2026 Aug 4. doi: 10.1097/ICO.0000000000004253. Online ahead of print.
PubMed 42635062Warner DB, Lee TF, Troxel AB, Prescott C, Cohen EJ, Jeng BH; ZEDS Trial Research Group. Time-Varying Effects of Valacyclovir Prophylaxis in the Zoster Eye Disease Study: A Post Hoc Exploratory Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2026 Aug 13:e263202. doi: 10.1001/jamaophthalmol.2026.3202. Online ahead of print.
PubMed 42593809Warner DB, Jeng BH, Kim J, Liu M, Troxel AB, Hochman JS, Baratz KH, Mian SI, Choulakian MY, Meyer JJ, Lu Y, Twi-Yeboah A, Lee TF, Lopez-Jimenez C, Laury SC, Cohen EJ; ZEDS Trial Research Group. Low-Dose Valacyclovir for Postherpetic Neuralgia in the Zoster Eye Disease Study: A Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):277-285. doi: 10.1001/jamaophthalmol.2024.6113.
PubMed 40048191Cohen EJ, Troxel AB, Liu M, Hochman JS, Baratz KH, Mian SI, Choulakian MY, Warner DB, Lu Y, Twi-Yeboah A, Lee TF, Kim J, Lopez-Jimenez C, Laury SC, Jeng BH; ZEDS Trial Research Group. Low-Dose Valacyclovir in Herpes Zoster Ophthalmicus: The Zoster Eye Disease Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):269-276. doi: 10.1001/jamaophthalmol.2024.6114.
PubMed 40048183Prescott CR, Cohen EJ, Hochman JS, Troxel AB, Lu Y, Twi-Yeboah A, Jimenez CL, Mian SI, Mazen CY, Warner DB, Baratz KH, Jeng BH; ZEDS Trial Research Group. Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study. Cornea. 2024 Dec 1;43(12):1473-1480. doi: 10.1097/ICO.0000000000003497.
PubMed 38411973Cohen EJ, Hochman JS, Troxel AB, Colby KA, Jeng BH; ZEDS Trial Research Group. Zoster Eye Disease Study: Rationale and Design. Cornea. 2022 May 1;41(5):562-571. doi: 10.1097/ICO.0000000000002743.
PubMed 35090154
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Suppressive Valacyclovir Treatment for Herpes Zoster Ophthalmicus
- ClinicalTrials.gov ID
- NCT03134196
- Acronym / sponsor ID
- ZEDS / 16-00463
- Conditions
- Herpes Zoster Ophthalmicus
- Keywords
- Herpes Zoster Ophthalmicus, Zoster Eye Disease Study, Varicella Zoster Virus, Zoster, Shingles
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 527 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Eye Institute (NEI), National Institutes of Health (NIH)
- Study start
- 23 Aug 2017 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 22 Jul 2024 (actual)
- First posted
- 28 Apr 2017 (actual)
- Results
- Posted 7 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, randomized, double-masked, placebo-controlled clinical trial of suppressive valacyclovir for one year in immunocompetent study participants with an episode of dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to Herpes Zoster Ophthalmicus (HZO) in the year prior to enrollment.
Detailed description
The objective of the Zoster Eye Disease Study (ZEDS) is to determine whether prolonged suppressive oral antiviral treatment with valacyclovir reduces complications of Herpes Zoster Ophthalmicus (HZO), thereby improving clinical outcomes in this common and potentially vision- and life-threatening disease. There are 1,000,000 new cases of Herpes Zoster (HZ) per year in the USA, with 10-20% being HZO.
Specific Aims
Primary Aim: The primary aim of this double-masked, placebo controlled multicenter randomized clinical trial will test the hypothesis that suppressive antiviral treatment for 12 months with oral valacyclovir 1000 mg daily reduces the rate of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or iritis compared to placebo, at 12 months as the primary endpoint, and at 18 months including 6 months of follow-up after treatment, as a secondary endpoint, in patients with HZO who have had an episode of one of these disease manifestations during the year prior to enrollment.
Secondary Aim: The second aim is to test the hypothesis that suppressive treatment for 12 months with oral valacyclovir 1000 mg daily reduces the severity and duration of postherpetic neuralgia (PHN), compared to placebo, at 12 months and at 18 months as secondary endpoints, in similar patients with HZO. PHN is a debilitating chronic pain syndrome that negatively impacts quality of life, especially in elderly patients.
The study will enroll immunocompetent patients age 18 years and older who have HZO diagnosed at variable times in the past, with these types of active anterior segment ocular segment disease within the past year. Eligible patients will be randomized in a 1:1 ratio to long-term suppressive treatment with oral valacyclovir 1000 mg daily or placebo for 12 months, plus usual ophthalmic care, and followed every 3 months for a total of 18 months, to determine outcomes of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or iritis and/or severity and duration of PHN during 12 months of treatment and for 6 months following treatment discontinuation. The results with regard to PHN may be applicable to HZ in other locations. If suppressive valacyclovir treatment is determined to be effective, the potentially devastating disease burden of HZO and HZ may be reduced for patients, as well as the annual costs to society, estimated in the USA to be one billion dollars.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Masked PlaceboEncapsulated masked placebo |
| Masked Oral Valacyclovir 1000 mg daily | Active comparator | Drug: Masked Oral ValacyclovirValacyclovir, 500 mg, oral pill, two 500mg pills daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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 |
|---|---|---|
| Masked PlaceboOral Placebo | Drug | Placebo |
| Masked Oral ValacyclovirAlso: ValtrexOral Valacyclovir 1000 mg/day | Drug | Masked Oral Valacyclovir 1000 mg daily |
Primary outcome
Number of Participants With the First Occurrence of New or Worsening Stromal Keratitis Without Ulceration (SK), Endothelial Keratitis (EK), Iritis (IR), Dendriform Epithelial Keratitis (DEK), or Stromal Keratitis With Ulceration (SKU)
Time frame: Month 12
The number of participants with the first confirmed endpoint (new or worsening SK, EK, IR, DEK or SKU associated with pre-specified definitions of these disease manifestations and associated treatment requirements within 12 months in study participants assigned to valacyclovir compared to placebo. Diagnostic criteria were defined using the classification for SK, EK, SKU, and DEK caused by Herpes Simplex Virus (HSV) and standardization of uveitis nomenclature (SUN) for IR. A substantial increase in topical steroid treatment, defined as starting, shifting from a lower to higher potency steroid, or doubling frequency of steroid at one visit (new) or gradually within 3 months (worsening) was required for SK, EK, IR, and SKU.
5 secondary outcomes
Number of Participants With Persistent Treatment Benefit at 18 Months, 6 Months After Cessation of Treatment
Time frame: Month 18 (6 months post treatment)
Number of Postherpetic Neuralgia (PHN) Episodes
Time frame: Month 12
Number of Postherpetic Neuralgia (PHN) Episodes
Time frame: Month 18 (6 months post treatment)
Average Duration of Postherpetic Neuralgia (PHN) Pain
Time frame: Month 24 (12 months post-treatment)
Average Duration of Postherpetic Neuralgia (PHN) Pain
Time frame: Month 30 (18 months post treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42635062Mian SI, Kim J, Troxel AB, Cohen EJ, Jeng BH; ZEDS Trial Research Group. Outcomes of Recombinant Zoster Vaccination in Herpes Zoster Ophthalmicus: A Secondary Analysis of the Zoster Eye Disease Study. Cornea. 2026 Aug 4. doi: 10.1097/ICO.0000000000004253. Online ahead of print.
- Derived from this study: PubMed 42593809Warner DB, Lee TF, Troxel AB, Prescott C, Cohen EJ, Jeng BH; ZEDS Trial Research Group. Time-Varying Effects of Valacyclovir Prophylaxis in the Zoster Eye Disease Study: A Post Hoc Exploratory Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2026 Aug 13:e263202. doi: 10.1001/jamaophthalmol.2026.3202. Online ahead of print.
- Derived from this study: PubMed 40048191Warner DB, Jeng BH, Kim J, Liu M, Troxel AB, Hochman JS, Baratz KH, Mian SI, Choulakian MY, Meyer JJ, Lu Y, Twi-Yeboah A, Lee TF, Lopez-Jimenez C, Laury SC, Cohen EJ; ZEDS Trial Research Group. Low-Dose Valacyclovir for Postherpetic Neuralgia in the Zoster Eye Disease Study: A Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):277-285. doi: 10.1001/jamaophthalmol.2024.6113.
- Derived from this study: PubMed 40048183Cohen EJ, Troxel AB, Liu M, Hochman JS, Baratz KH, Mian SI, Choulakian MY, Warner DB, Lu Y, Twi-Yeboah A, Lee TF, Kim J, Lopez-Jimenez C, Laury SC, Jeng BH; ZEDS Trial Research Group. Low-Dose Valacyclovir in Herpes Zoster Ophthalmicus: The Zoster Eye Disease Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):269-276. doi: 10.1001/jamaophthalmol.2024.6114.
- Derived from this study: PubMed 38411973Prescott CR, Cohen EJ, Hochman JS, Troxel AB, Lu Y, Twi-Yeboah A, Jimenez CL, Mian SI, Mazen CY, Warner DB, Baratz KH, Jeng BH; ZEDS Trial Research Group. Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study. Cornea. 2024 Dec 1;43(12):1473-1480. doi: 10.1097/ICO.0000000000003497.
- Derived from this study: PubMed 35090154Cohen EJ, Hochman JS, Troxel AB, Colby KA, Jeng BH; ZEDS Trial Research Group. Zoster Eye Disease Study: Rationale and Design. Cornea. 2022 May 1;41(5):562-571. doi: 10.1097/ICO.0000000000002743.
- Study websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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.
Elisabeth Cohen, MD study chair
NYU Langone Health
78 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Masked Oral Valacyclovir in people with Herpes Zoster Ophthalmicus, run by NYU Langone Health at 78 sites in 2 countries.
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: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Number of Participants With the First Occurrence of New or Worsening Stromal Keratitis Without Ulceration (SK), Endothelial Keratitis (EK), Iritis (IR), Dendriform Epithelial Keratitis (DEK), or Stromal Keratitis With Ulceration (SKU) (time frame: Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03134196, which also lists 6 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 7 Mar 2025.