Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

To be eligible for study participation, an individual must meet all of the following criteria:

1. Ability to understand, and willingness and ability to read and sign, the informed consent form.

2. Ability to understand and follow instructions and study procedures.

3. Willingness to comply with all study procedures and be available for the duration of the study.

4. Ability to take oral medication, and are willing to adhere to study medication regimen.

5. Age 18 years or older.

6. Diagnosed with HZO in one eye based on both of these criteria:

1. History of characteristic unilateral, usually vesicular, HZO rash in the dermatomal distribution of cranial nerve V1 or V2.

2. 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.

i. 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.

7. 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:

1. History of immunocompromised status as defined by current CDC contraindications for the vaccine against zoster (44).

1. 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.

2. 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.

3. Study participants on immunosuppressive therapy including:

i. 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.

2. 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.

3. Renal insufficiency:

1. Requires dialysis or has history of renal transplant or

2. eGFR less than 45, determined within 3 months days preceding enrollment.

4. Allergy or adverse reaction to valacyclovir or acyclovir.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. Incarceration

11. 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.

12. 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.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo
Encapsulated masked placebo
  • Drug: Masked Placebo
    Oral Placebo
Active Comparator
Masked Oral Valacyclovir 1000 mg daily
Valacyclovir, 500 mg, oral pill, two 500mg pills daily
  • Drug: Masked Oral Valacyclovir
    Oral Valacyclovir 1000 mg/day
    Other names:
    • Valtrex

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233
Contact:
Lindsay Gregg
205-488-0777
lindsaygregg@uabmc.edu

Mayo Clinic - Arizona
Scottsdale, Arizona 85259
Contact:
Emily Branch
480-301-9392
Branch.Emily@mayo.edu

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Lyndsay Dupree
501-296-1156
LLDupree@uams.edu

Scripps Clinic
La Jolla, California 92037
Contact:
Daphne Breshears
858-554-9611
Breshears.Daphne@scrippshealth.org

Loma Linda University Eye Institute
Loma Linda, California 92354
Contact:
Raquel Hernandez
909-558-2168
raqhernandez@llu.edu

Jules Stein Eye Clinic - UCLA
Los Angeles, California 90095
Contact:
Omar Levya
310-794-5604
OmarLeyva@mednet.ucla.edu

Byers Eye Institute at Stanford University
Palo Alto, California 94303
Contact:
Lisa Greer
650-725-9184
lgreer7@stanford.edu

UCSF- Francis I. Proctor Foundation
San Francisco, California 94131
Contact:
Sarah Lopez
979-229-4895
sarah.lopez@ucsf.edu

Pacific Eye Surgeons, Inc.
San Luis Obispo, California 93401
Contact:
Gabriela A Navarro
805-503-1016
GNavarro@paceyemd.com

University of Colorado
Aurora, Colorado 80045
Contact:
Mary Preston
720-848-2035
mary.preston@ucdenver.ed

Colorado Cornea Consultants P.C.
Littleton, Colorado 80120
Contact:
Breanna Nickels
720-709-7533
bnickels@corneaonline.com

Medstar Georgetown University Hospital
Washington, District of Columbia 20007
Contact:
Lisa Thompson
202-444-7237
thompsol@gunet.georgetown.edu

Delray Eye Associates, PA
Delray Beach, Florida 33484
Contact:
Ellen Salvati
561-498-8100
ellens@delrayeye.com

University of Florida
Gainesville, Florida 32610
Contact:
Shannon Hampton
352-373-8787
thists@shands.ufl.edu

Florida Eye Specialists
Jacksonville, Florida 33204
Contact:
Jillian M Smith
904-564-2020
jsmith@floridaeyespecialists.com

University of Miami - Bascom Palmer Eye Institute
Miami, Florida 33136
Contact:
JoAnne O'Day
305-326-6508
j.oday@miami.edu

Eye Consultants of Atlanta, PC
Atlanta, Georgia 30339
Contact:
Teresa A Long
404-351-2220
teresa_long@eyeconsultants.net

University of Illinois
Chicago, Illinois 60612
Contact:
Joseph Baker
312-996-7204
jbaker7@uic.edu

NorthShore University Health System
Glenview, Illinois 60026
Contact:
Mira Shiloach
847-657-1750
mshiloach@northshore.org

Case Western Reserve University
Cleveland, Indiana 44106
Contact:
Sangeetha Raghupathy
216-844-8552
Sangeetha.Raghupathy@uhhospitals.org

Indiana University - Glick Eye Institute
Indianapolis, Indiana 46202
Contact:
Linda Morgan
317-274-2277
lismorga@iupui.edu

University of Kansas Medical Center
Prairie Village, Kansas 66208
Contact:
Ashley Small, MPH
913-588-0105
asmall2@kumc.edu

University of Kentucky
Lexington, Kentucky 40509
Contact:
Michele Reg
859-323-5868
mreg4@uky.edu

LSU Health Science Center
New Orleans, Louisiana 70112
Contact:
James Outland
504-568-7634
joutla@lsuhsc.edu

Shreveport Eye Clinic
Shreveport, Louisiana 71106
Contact:
Tammy Stephens
318-861-4080
tstephens@shreveporteyeclinic.com

University of Maryland
Baltimore, Maryland 21201
Contact:
Alfred Vinnett, MD
667-214-1161
AVinnett@som.umaryland.edu

The Krieger Eye Institute
Baltimore, Maryland 21215
Contact:
B. Nichole Rusk
410-601-7643
brusk@lifebridgehealth.org

Wilmer Eye Institute John Hopkins
Bethesda, Maryland 20817
Contact:
Sabtina Jenkins
443-546-1558
sjenki43@jhmi.edu

Crossroads Eye Physician
Owings Mills, Maryland 21117
Contact:
Deborah Herman
410-581-1500
kerkerd@gmail.com

Tufts Medical Center
Boston, Massachusetts 02111
Contact:
Michael Dixon
617-636-1051
mdixon3@tuftsmedicalcenter.org

Massachusetts Eye and Ear Infirmary
Boston, Massachusetts 02114
Contact:
John Caccaviello
617-573-4436
John_Caccaviello@MEEI.HARVARD.EDU

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Marissa Fiorello
617-414-8848
Marissa.Fiorello@bmc.org

Lahey Medical Center
Peabody, Massachusetts 01960
Contact:
Christine Gould
978-538-4412
christine.gould@lahey.org

Eye Health Services
Weymouth, Massachusetts 02189
Contact:
Erica Wasil
617-472-5442
ewasil@eyehealthservices.com

University of Michigan
Ann Arbor, Michigan 48105
Contact:
Munira Hussain
734-647-8397
hussain@med.umich.edu

Verdier Eye Center
Grand Rapids, Michigan 49546
Contact:
Paula Johnson
616-949-2001
PJohnson@vecgr.com

Northwest Eye Clinic
Golden Valley, Minnesota 55427
Contact:
Jennifer Burdick
952-567-6111
jaburdick@nweyeclinic.com

Jennifer Burdick
Minnetonka, Minnesota 55305
Contact:
Jennifer Burdick
952-567-6111
jaburdick@mneye.com

Mayo Clinic
Rochester, Minnesota 55905
Contact:
Hamad Gul
507-284-5833
hamad.gul@mayo.edu

Washington University Opthalmology
Saint Louis, Missouri 63110
Contact:
Casey Hatscher
314-747-5832
chatscher@wustl.edu

Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire 03756
Contact:
Christine Toutain-Kidd
603-650-0556
christine.m.toutain-kidd@hitchcock.org

EyeCare MD of NJ
Morristown, New Jersey 07960
Contact:
Heather Ademovic
973-984-3937
frontdesk@eyecaremdnj.com

Albany Stratton VA Medical Center
Albany, New York 12208
Contact:
Leahruth Saavedra
518-626-6501
leahruth.saavedra@va.gov

Finger Lakes Ophthalmology /The Eye Care Center
Canandaigua, New York 14424
Contact:
Stacy Mahoney
585-391-1181
stacymahaney@eyecarectr.com

Stony Brook Ophthalmology
East Setauket, New York 11733
Contact:
Ann Marie Lavorna
631-444-4090
ann.lavorna@stonybrook.edu

Northwell Health
Great Neck, New York 11021
Contact:
Sajana Sivagnaman
516-881-7046
ssivagnanam@northwell.edu

New York Eye and Ear Infirmary
New York, New York 10003
Contact:
Harriet lloyd
212-979-4672
Harriet.Lloyd@mountsinai.org

NYU Langone Health
New York, New York 10016
Contact:
Tonya Robin
929-455-5041
Tonya.Robin@nyulangone.org

Weill Cornell Ophthalmology
New York, New York 10021
Contact:
Susan Herder
646-962-4118
herders@med.cornell.edu

Duke University
Durham, North Carolina 27710
Contact:
Elmer Balajonda
919-684-4418
elmer.balajonda@duke.edu

Cincinnati Eye Institute
Cincinnati, Ohio 45242
Contact:
Kelye Conrad
513-569-3462
kconrad@cincinnatieye.com

Case Western Reserve University
Cleveland, Ohio 44106
Contact:
Sangeetha Raghupathy
216-844-8552
Sangeetha.Raghupathy@uhhospitals.org

Devers Eye Institute
Portland, Oregon 97210
Contact:
Alex Bauer
503-413-6937
alex@visiongift.org

Casey Eye Institute - Oregon Health and Science University
Portland, Oregon 97239
Contact:
Jennifer Maykoski
503-494-0482
maykoski@ohsu.edu

Vantage Eye Care Center, LLC
Bala-Cynwyd, Pennsylvania 19004
Contact:
Gwen Toti
484-434-2706
gtoti@oppdoctors.com

Geisinger Eye Clinic
Danville, Pennsylvania 17822
Contact:
Marie A Kleman
570-214-6070
mkleman@geisinger.edu

University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Adrienne Saludades
215-662-8091
Adrienne.Saludades@uphs.upenn.edu

Corneal Associates at Wills Eye Hospital
Philadelphia, Pennsylvania 19107
Contact:
Heather Caffey
215-928-3180
corneatech@willseye.org

University of Tennessee - Hamilton Eye Institute
Memphis, Tennessee 38163
Contact:
Ellen Fleetwood
901-448-1299
emesseng@.utk.edu

Cornea and Cataract Consultants of Nashville
Nashville, Tennessee 37203
Contact:
Shannon Reid
615-320-7200
sreid@corneaconsultants.net

Vanderbilt Eye Institute
Nashville, Tennessee 37232
Contact:
Scott Ruark
615-936-1639
scott.ruark@vanderbilt.edu

Cornea Associates of Texas
Dallas, Texas 75231
Contact:
Jennifer De Los Santos
214-696-0146
jdelossantos@corneatexas.com

University of Texas Southwestern
Dallas, Texas 75390
Contact:
Yesenia Leach
214-645-2012
Yesenia.Leach@UTSouthwestern.edu

Cornea Consultants of Texas
Fort Worth, Texas 76107
Contact:
Jessica Yarborough
817-529-3100
yarborough@corneaconsultantstx.com

Alkek Eye Center - Baylor College of Medicine
Houston, Texas 77030
Contact:
April Leger
713-798-4123
April.Leger@bcm.edu

R and R Eye Research, LLC
San Antonio, Texas 78229
Contact:
Catherine (Maggie) Hazen
210-424-2584
maggie@rreyes.net

University of Utah - Moran Eye Center
Salt Lake City, Utah 84132
Contact:
Susan Allman
801-585-6647
Susan.Allman@hsc.utah.edu

Virginia Eye Institute
Richmond, Virginia 23226
Contact:
Lea Anderlini
804-287-4219
anderlinil@vaeye.com

NY Eye Surgeons
Seattle, Washington 98133
Contact:
Hannah Seo
206-528-6000
hannah.seo@nweyes.com

University of Wisconsin - Madison
Madison, Wisconsin 53705
Contact:
Kristine Dietzman
608-262-6222
kadietzman@wisc.edu

More Details

NCT ID
NCT03134196
Status
Recruiting
Sponsor
NYU Langone Health

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.