Herpes SimplexPhase 3NCT00001649
Valaciclovir to Prevent Transmission of Herpes Simplex Virus
A Phase 3 study testing Valaciclovir in people with Herpes Simplex, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will evaluate the effectiveness of the drug valaciclovir in preventing transmission of genital herpes from an infected to an uninfected sexual partner. Genital herpes is caused by the herpes simplex virus 2 (HSV-2), or, infrequently herpes simplex virus 1 (HSV-1). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Herpes Simplex
- What is being tested?
- Valaciclovir
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1997to Aug 2003
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 15Show fewer
- 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.
- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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).
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Evaluation of Valaciclovir for the Prevention of Herpes Simplex Virus Transmission in Heterosexual Couples
This study will evaluate the effectiveness of the drug valaciclovir in preventing transmission of genital herpes from an infected to an uninfected sexual partner. Genital herpes is caused by the herpes simplex virus 2 (HSV-2), or, infrequently herpes simplex virus 1 (HSV-1). Valaciclovir prevents the herpes virus from multiplying and may also reduce its transmission between partners.
Couples 18 years of age and older in which one partner is infected with HSV-2 (source partner) and the other is not (susceptible partner), may be eligible for this study. Candidates will be screened with blood tests for routine laboratory studies and to verify the presence or absence of HSV-2 or HSV-1 infection.
Read more
Participants will give a medical history, undergo a physical examination, including genital examination, and receive counseling on safer sex practices and how to recognize signs and symptoms of a possible first episode of genital herpes. Source partners will also be counseled on transmission of genital herpes, and susceptible partners will be interviewed about their sexual history and practices. The source partner will be randomly assigned to take either a 500-mg tablet of valaciclovir or placebo (a pill with no active ingredient) daily for 8 months. All participants will be given diary cards to complete for a month-the source partner will record any drug side effects and the susceptible partner will record any signs or symptoms of possible HSV infection.
Participants will be seen in the clinic once a month for 8 months. At these visits, source partners will 1) return unused study medication and the completed diary card; 2) discuss any adverse drug side effects experienced in the last month; 3) review medications other than the study drug taken in the last month; 4) undergo counseling on safer sex practices, transmission of genital herpes, and recognizing signs and symptoms of a first episode of genital herpes; and 5) review symptoms and recurrences of genital herpes experienced during the last month. During the final visit, they will also provide a blood sample for routine testing and possible use in future studies. Susceptible partners will 1) have a blood sample drawn for HSV testing; 2) undergo safer sex counseling; 3) review any symptoms experienced over the last month; 4) be interviewed about sexual exposure and practices; and 5) return the completed diary card.
Source partners who have a recurrence of genital HSV while on the study will be asked to have their lesions cultured and will be offered open-label valaciclovir treatment. Susceptible partners who contract genital herpes from the source partner during the study will have a genital examination to verify a fist episode of genital herpes and will receive 10 days of open-label treatment with valaciclovir. Cultures will be taken from the mouth and genitals, current medical conditions will be reviewed, blood samples will be drawn on treatment days 1 and 10, and treatment side effects will be reviewed on days 5 and 10.
At the end of the study, infected partners will be offered a 12-month course of valaciclovir, one 500-mg tablet daily. Participants will be followed in the clinic once every 3 months to provide blood samples, return unused study medication and the diary card, discuss any drug side effects, review medications taken besides the study drug, and review symptoms or recurrences of genital herpes.
All participants will be asked to complete a questionnaire for gathering information about people with genital herpes and people at risk for the infection.
Read the detailed description
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.
- Conditions
- Herpes Simplex
- Being tested
- Valaciclovir
- Keywords
- Clinical Trial, Sexual Transmitted Disease, Phase III, HSV, Valtrex, Valaciclovir, HS2A/B3009, Herpes Simplex Virus Transmission, Heterosexual Couples
- Medical subject headings
- Herpes Simplex, Sexually Transmitted Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValaciclovirDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startAug 1997
- Study completionAug 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Herpes SimplexStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 3
- Primary purpose
- Treatment
- Enrolment
- 180 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001649
- Sponsor's protocol ID
- 970168
- Other IDs
- 97-I-0168
- Status last verified
- Aug 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Wagner HU, Van Dyck E, Roggen E, Nunn AJ, Kamali A, Schmid DS, Dobbins JG, Mulder DW. Seroprevalence and incidence of sexually transmitted diseases in a rural Ugandan population. Int J STD AIDS. 1994 Sep-Oct;5(5):332-7. doi: 10.1177/095646249400500509.
PubMed 7819350Greenblatt RM, Lukehart SA, Plummer FA, Quinn TC, Critchlow CW, Ashley RL, D'Costa LJ, Ndinya-Achola JO, Corey L, Ronald AR, et al. Genital ulceration as a risk factor for human immunodeficiency virus infection. AIDS. 1988 Feb;2(1):47-50. doi: 10.1097/00002030-198802000-00008.
PubMed 3128996Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992 Feb 1;116(3):197-202. doi: 10.7326/0003-4819-116-3-197.
PubMed 1309413
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Evaluation of Valaciclovir for the Prevention of Herpes Simplex Virus Transmission in Heterosexual Couples
- ClinicalTrials.gov ID
- NCT00001649
- Acronym / sponsor ID
- 970168
- Conditions
- Herpes Simplex
- Keywords
- Clinical Trial, Sexual Transmitted Disease, Phase III, HSV, Valtrex, Valaciclovir, HS2A/B3009, Herpes Simplex Virus Transmission
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Aug 1997
- Study completion
- Aug 2003
- First posted
- 4 Nov 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.
This study will evaluate the effectiveness of the drug valaciclovir in preventing transmission of genital herpes from an infected to an uninfected sexual partner. Genital herpes is caused by the herpes simplex virus 2 (HSV-2), or, infrequently herpes simplex virus 1 (HSV-1). Valaciclovir prevents the herpes virus from multiplying and may also reduce its transmission between partners.
Couples 18 years of age and older in which one partner is infected with HSV-2 (source partner) and the other is not (susceptible partner), may be eligible for this study. Candidates will be screened with blood tests for routine laboratory studies and to verify the presence or absence of HSV-2 or HSV-1 infection.
Participants will give a medical history, undergo a physical examination, including genital examination, and receive counseling on safer sex practices and how to recognize signs and symptoms of a possible first episode of genital herpes. Source partners will also be counseled on transmission of genital herpes, and susceptible partners will be interviewed about their sexual history and practices. The source partner will be randomly assigned to take either a 500-mg tablet of valaciclovir or placebo (a pill with no active ingredient) daily for 8 months. All participants will be given diary cards to complete for a month-the source partner will record any drug side effects and the susceptible partner will record any signs or symptoms of possible HSV infection.
Participants will be seen in the clinic once a month for 8 months. At these visits, source partners will 1) return unused study medication and the completed diary card; 2) discuss any adverse drug side effects experienced in the last month; 3) review medications other than the study drug taken in the last month; 4) undergo counseling on safer sex practices, transmission of genital herpes, and recognizing signs and symptoms of a first episode of genital herpes; and 5) review symptoms and recurrences of genital herpes experienced during the last month. During the final visit, they will also provide a blood sample for routine testing and possible use in future studies. Susceptible partners will 1) have a blood sample drawn for HSV testing; 2) undergo safer sex counseling; 3) review any symptoms experienced over the last month; 4) be interviewed about sexual exposure and practices; and 5) return the completed diary card.
Source partners who have a recurrence of genital HSV while on the study will be asked to have their lesions cultured and will be offered open-label valaciclovir treatment. Susceptible partners who contract genital herpes from the source partner during the study will have a genital examination to verify a fist episode of genital herpes and will receive 10 days of open-label treatment with valaciclovir. Cultures will be taken from the mouth and genitals, current medical conditions will be reviewed, blood samples will be drawn on treatment days 1 and 10, and treatment side effects will be reviewed on days 5 and 10.
At the end of the study, infected partners will be offered a 12-month course of valaciclovir, one 500-mg tablet daily. Participants will be followed in the clinic once every 3 months to provide blood samples, return unused study medication and the diary card, discuss any drug side effects, review medications taken besides the study drug, and review symptoms or recurrences of genital herpes.
All participants will be asked to complete a questionnaire for gathering information about people with genital herpes and people at risk for the infection.
Detailed description
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
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 |
|---|---|---|
| Valaciclovir | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7819350Wagner HU, Van Dyck E, Roggen E, Nunn AJ, Kamali A, Schmid DS, Dobbins JG, Mulder DW. Seroprevalence and incidence of sexually transmitted diseases in a rural Ugandan population. Int J STD AIDS. 1994 Sep-Oct;5(5):332-7. doi: 10.1177/095646249400500509.
- Background: PubMed 3128996Greenblatt RM, Lukehart SA, Plummer FA, Quinn TC, Critchlow CW, Ashley RL, D'Costa LJ, Ndinya-Achola JO, Corey L, Ronald AR, et al. Genital ulceration as a risk factor for human immunodeficiency virus infection. AIDS. 1988 Feb;2(1):47-50. doi: 10.1097/00002030-198802000-00008.
- Background: PubMed 1309413Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992 Feb 1;116(3):197-202. doi: 10.7326/0003-4819-116-3-197.
Related trials for Herpes Simplex
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1/2
Clinical Trial of Recombinant Herpes Zoster Vaccine (ZFA01 Adjuvant, CHO Cells)
Herpes Zoster
Active, not recruitingPhase 2
A Phase 2 Study to Evaluate JCXH-105, an srRNA-based Herpes Zoster Vaccine
Herpes Zoster (HZ), Infectious Diseases
RecruitingPhase 1/2
Safety and Immunogenicity of Recombinant Varicella Zoster Virus Vaccine in People With HIV Who Have a CD4 Count Less Than 300 or Greater Than or Equal to 300 and a Healthy Control Population
Herpes Zoster
Not yet recruitingPhase 2
Study to Compare GS-1179 Versus Valacyclovir in HSV-2 Seropositive Participants With Recurrent Genital Herpes
HSV-2 Infection
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Valaciclovir in people with Herpes Simplex, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. 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 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 NCT00001649, which also lists 3 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 4 Mar 2008.