A Randomized, Double-Blind, Placebo-Controlled Evaluation of Valaciclovir for the Prevention of Herpes Simplex Virus Transmission in Heterosexual Couples
Valaciclovir
Urogenital Diseases+13
+ Genital Diseases
+ Communicable Diseases
Treatment Study
Summary
Study start date: August 1, 1997
Actual date on which the first participant was enrolled.This is a randomized, multicenter, double-blind, placebo-controlled Phase III study to evaluate the effect of valaciclovir in preventing the transmission of herpes simplex virus (HSV) in heterosexual couples discordant for the presence of herpes simplex type 2 virus (HSV-2) antibody. The seropositive source partner will be randomized to receive valaciclovir 500 mg once daily or placebo for 8 months, and the susceptible seronegative partner will be monitored for clinical and subclinical (serological) acquisition of HSV. Couples must be 18 years of age or older, in general good health, and in a monogamous relationship with each other. Source partners must be seropositive for HSV-2, have a history of genital herpes recurrences, and experiencing less than 10 recurrences per year, and be off suppressive therapy upon entry into the study. Susceptible partners must be HSV-2 seronegative. The couple will be stratified based on gender and HSV status of the susceptible partner in a 2:2:1:1 ratio [HSV-1 negative female: HSV-1 positive female: HSV-1 negative male: HSV-1 positive male]. They will then be randomized to either valaciclovir 500 mg once daily or placebo (1:1 randomization) within each stratum. The primary endpoint is the proportion of couples with clinical evidence of a first episode of genital HSV in the susceptible partner with laboratory confirmation. Secondary endpoints will be time to clinical symptoms of genital HSV by the susceptible partner, time to seroconversion in the susceptible partner, and time to first recurrence of HSV in the source partner. A total of 1500 couples will be randomized into the study. Assuming a 3% incidence in the placebo arm and a reduction of 75% in the risk of showing clinical evidence of genital HSV, this study will have at least 80% power for a two-tailed test at the 5% level of significance. The safety and tolerance of valaciclovir will be assessed by laboratory evaluation and by occurrence and nature of adverse events. The study will be conducted at approximately 35 outpatient centers in the United States, Canada and Europe, therefore it is expected that each center will enroll between 40 to 60 couples.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.180 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
INCLUSION CRITERIA - SOURCE PARTNER 18 years of age or older. General good health as determined by current medical status and laboratory tests. Active heterosexual relationship with susceptible partner. Presence of HSV-2 serum antibody as determined by Western blot analysis. History of symptomatic recurrent genital herpes. Off HSV suppressive therapy upon entering study. In the opinion of the investigator, able to comply with protocol requirements. In the investigator's opinion, subjects must be candidates for receiving suppressive therapy for management of their disease. Written informed consent. EXCLUSION CRITERIA - SOURCE PARTNER: Patients who are known or suspected to be immunocompromised (e.g., patients receiving immunosuppressive therapy, patients with malignancy or seropositive for HIV). Subjects with a history of 10 or more HSV recurrences per year. Impaired renal function as defined by serum creatinine greater than 1.5 mg/dL or estimated creatinine clearance less than 30 ml/min. Impaired hepatic function defined as an alanine transaminase (ALT) level greater than 3 times the normal upper limit. Known resistance to aciclovir, famciclovir, or ganciclovir. Known hypersensitivity to aciclovir, valaciclovir, famciclovir, or ganciclovir. Malabsorption syndrome or other gastrointestinal dysfunction that might impair drug dynamics. Subjects known to be lactose intolerant. Women contemplating pregnancy within the duration of study drug dosing for this study. Women of child bearing potential not using an effective method of contraception. Positive pregnancy test (or pregnant females or nursing mothers). INCLUSION CRITERIA - SUSCEPTIBLE PARTNER 18 years of age or older. General good health as determined by current medical status. Active monogamous, heterosexual relationship with source partner. Absence of HSV-2 serum antibody as determined by Western blot analysis. In the investigator's opinion, able to comply with protocol requirements. Written informed consent. EXCLUSION CRITERIA - SUSCEPTIBLE PARTNER: Subjects who are known or suspected to be immunocompromised (e.g., patients receiving immunosuppressive therapy, patients with malignancy or seropositive for HIV). Subjects who have received an active HSV vaccine (subjects known to have received placebo in clinical trials are eligible). Presence of symptomatic genital herpes. Subjects having sexual relations with anyone other than the source partner. Women contemplating pregnancy within the time period of the study. Women of childbearing potential not using an effective method of contraception. Positive pregnancy test (or pregnant females or nursing mothers).
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, United StatesOpen National Institute of Allergy and Infectious Diseases (NIAID) in Google Maps