HIV InfectionPhase 3VALIDATENCT00860977
Can Valacyclovir Delay the Need for Initiation of Human Immunodeficiency Virus (HIV) Treatment in HIV-infected Individuals?
A Phase 3 study testing valacyclovir in people with HIV Infection and Herpes Simplex Type II, run by University Health Network, Toronto at 25 sites in 4 countries.
Trial summary
This study is a multicentre, randomized, placebo-controlled, fully blinded, clinical trial of twice daily oral valacyclovir 500mg versus placebo with the goal of delaying the need for initiating HAART among HIV infected individuals who neither use nor require HAART, and who have not used chronic suppressive anti-HSV… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, Herpes Simplex Type II, HIV Infections
- What is being tested?
- valacyclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 202 participants
- Where
- 25 sitesin 4 countries
- Study dates
- Mar 2010to Aug 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult (aged 18 years or older or as per Local/Provincial Guidelines)
- documented HIV-1 infection (determined by EIA and Western blot, sites' standard assays are acceptable if approved in advance by the PIs for the study, Dr. Darrell Tan and/or Dr. Sharon Walmsley)
- no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
- antiretroviral naïve (no more than 14 days of total prior ARV exposure)
- CD4 count within the 400-900 cells/mm3 range (inclusive) on two consecutive occasions, with at least one measurement within 30 days of initiating trial (baseline visit)
- does not meet recommendations for initiating ARV therapy according to current guidelines
Who cannot join
- pregnancy or actively planning to become pregnant
- receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
- Estimated creatinine clearance <30 mL/min
- Other medical condition likely to cause death within 24 months
- Enrolled in a therapeutic HIV vaccine or immunotherapy trial
- Enrolled in another trial investigating the impact of another intervention on HIV disease progression
- HIV elite controller (EC), phenotypically defined here as documented duration of HIV infection of ≥5 years, a persistent CD4 cell count ≥500 cells/mm3, and a persistent plasma HIV viral load of <1000 copies/mL in the absence of antiretroviral therapy
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
Canada17 sites
University of Alberta
Edmonton, Alberta, T6G 2C8
CDHA, QEII Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9
McMaster University Health Sciences Centre
Hamilton, Ontario, L8N 3Z5
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2L 4M1
Montreal Chest Institute
Montreal, Quebec, H2X 2P4
The Ottawa Hospital, General Campus Divsions of Infectious Diseases
Ottawa, Ontario, K1H 8L6
University of Ottawa Health Services
Ottawa, Ontario, K1N 6N5
Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
Québec, G1V 4G2
Sunnybrook Health Science Centre
Toronto, Ontario, M2N 3M5
St. Clair Medical Associates
Toronto, Ontario, M4K 1N1
Maple Leaf Medical Clinic
Toronto, Ontario, M5B 1L6
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
University Health Network
Toronto, Ontario, M5G 2N2
B.C. Women's Hospital & Health Centre - Oak Tree Clinic
Vancouver, British Columbia, V6H 1N1
Vancouver Infectious Disease Clinic
Vancouver, British Columbia, V6Z 2C7
Cool Aid Community Health Centre
Victoria, British Columbia, V8W 1M8
Windsor Regional Hospital
Windsor, Ontario, N8W 1E3
United Kingdom4 sites
Brighton & Sussex University Hospitals NHS Trust
Brighton, BN2 1ES
Guy's and St. Thomas' NHS Foundation Trust
London, SE1 7EH
St. Stephen's AIDS Trust
London, SW10 9NH
St. Mary's Hospital
London, W2 1NY
Brazil3 sites
Instituto de Pesquisa Clínica Evandro Chagas
Rio de Janeiro
Ambulatorio de Infectologia da UNIFESP
São Paulo, 04040-002
Centro de Referencia e Treinamento em DST/AIDS
São Paulo, 04121-000
About this study
Official title: VALacyclovir In Delaying Antiretroviral Treatment Entry
This study is a multicentre, randomized, placebo-controlled, fully blinded, clinical trial of twice daily oral valacyclovir 500mg versus placebo with the goal of delaying the need for initiating HAART among HIV infected individuals who neither use nor require HAART, and who have not used chronic suppressive anti-HSV therapy for at least the 6 months prior to study initiation.
- Conditions
- HIV Infection, Herpes Simplex Type II, HIV Infections
- Being tested
- valacyclovir, Placebo
- Keywords
- HIV, Herpes simplex virus type II, Genital herpes, Treatment Naive
- Medical subject headings
- HIV Infections, Herpes Genitalis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
valacyclovirDrug
Also called Valtrex
oral valacyclovir 500mg twice daily
PlaceboDrug
Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily Receives: Drug: Placebo |
| Valacyclovir | Experimental | oral valacyclovir 500mg twice daily Receives: Drug: valacyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time.
Measured: up to 5 years
Secondary outcomes (7)
time from baseline until reaching the composite of either a CD4 cell count ≤350 cells/mm3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
Measured: up to 5 years
Annual rate of change in the CD4 cell count percentage, calculated as the slope of the participants' CD4 count percentage change over time
Measured: up to 5 years
Log10 plasma HIV viral load at 12, 24 and 36 months of follow-up
Measured: up to 5 years
Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine)
Measured: up to 5 years
Frequency of episodes of HSV reactivations at any anatomic site
Measured: up to 5 years
Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV
Measured: up to 5 years
Overall quality of life as measured by the MOS-HIV questionnaire at each 6-monthly time point
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2009 (estimated)
- Study startMar 2010
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- CIHR Canadian HIV Trials Network
- Responsible party
- Sponsor
- Investigators
- Sharon L Walmsley, MD FRCPC MSc, Principal investigator, University Health Network, TorontoDarrell HS Tan, MD FRCPC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00860977
- Sponsor's protocol ID
- CTN 240
- Other IDs
- ISRCTN66756285
- Acronym
- VALIDATE
- Status last verified
- Mar 2018
- First submitted
- 11 Mar 2009
- Last updated
- 6 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tan DH, Raboud JM, Kaul R, Grinsztejn B, Cahn P, Walmsley SL. Can herpes simplex virus type 2 suppression slow HIV disease progression: a study protocol for the VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial. Trials. 2010 Nov 24;11:113. doi: 10.1186/1745-6215-11-113.
PubMed 21106086
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VALacyclovir In Delaying Antiretroviral Treatment Entry
- ClinicalTrials.gov ID
- NCT00860977
- Acronym / sponsor ID
- VALIDATE / CTN 240
- Conditions
- HIV Infection, Herpes Simplex Type II, HIV Infections
- Keywords
- HIV, Herpes simplex virus type II, Genital herpes, Treatment Naive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 202 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- CIHR Canadian HIV Trials Network
- Study start
- Mar 2010 (actual)
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 13 Mar 2009 (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 is a multicentre, randomized, placebo-controlled, fully blinded, clinical trial of twice daily oral valacyclovir 500mg versus placebo with the goal of delaying the need for initiating HAART among HIV infected individuals who neither use nor require HAART, and who have not used chronic suppressive anti-HSV therapy for at least the 6 months prior to study initiation.
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: PlaceboOdourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily |
| Valacyclovir | Experimental | Drug: valacycloviroral valacyclovir 500mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- adult (aged 18 years or older or as per Local/Provincial Guidelines)
- documented HIV-1 infection (determined by EIA and Western blot, sites' standard assays are acceptable if approved in advance by the PIs for the study, Dr. Darrell Tan and/or Dr. Sharon Walmsley)
- no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
- antiretroviral naïve (no more than 14 days of total prior ARV exposure)
- CD4 count within the 400-900 cells/mm3 range (inclusive) on two consecutive occasions, with at least one measurement within 30 days of initiating trial (baseline visit)
Key exclusion criteria (7 listed)
- pregnancy or actively planning to become pregnant
- receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
- Estimated creatinine clearance <30 mL/min
- Other medical condition likely to cause death within 24 months
- Enrolled in a therapeutic HIV vaccine or immunotherapy trial
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 |
|---|---|---|
| valacyclovirAlso: Valtrexoral valacyclovir 500mg twice daily | Drug | Valacyclovir |
| PlaceboOdourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily | Drug | Placebo |
Primary outcome
annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time.
Time frame: up to 5 years
7 secondary outcomes
time from baseline until reaching the composite of either a CD4 cell count ≤350 cells/mm3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
Time frame: up to 5 years
Annual rate of change in the CD4 cell count percentage, calculated as the slope of the participants' CD4 count percentage change over time
Time frame: up to 5 years
Log10 plasma HIV viral load at 12, 24 and 36 months of follow-up
Time frame: up to 5 years
Treatment-emergent adverse events and laboratory abnormalities (CBC, serum creatinine)
Time frame: up to 5 years
Frequency of episodes of HSV reactivations at any anatomic site
Time frame: up to 5 years
Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed acyclovir-resistant HSV
Time frame: up to 5 years
Overall quality of life as measured by the MOS-HIV questionnaire at each 6-monthly time point
Time frame: up to 5 years
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 6 Mar 2018.
- Background: PubMed 21106086Tan DH, Raboud JM, Kaul R, Grinsztejn B, Cahn P, Walmsley SL. Can herpes simplex virus type 2 suppression slow HIV disease progression: a study protocol for the VALacyclovir In Delaying Antiretroviral Treatment Entry (VALIDATE) trial. Trials. 2010 Nov 24;11:113. doi: 10.1186/1745-6215-11-113.
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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.
Sharon L Walmsley, MD FRCPC MSc principal investigator
University Health Network, Toronto
Darrell HS Tan, MD FRCPC principal investigator
University Health Network, Toronto
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing valacyclovir in people with HIV Infection and Herpes Simplex Type II, run by University Health Network, Toronto at 25 sites in 4 countries.
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 6 inclusion and 7 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 6 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Canada, United Kingdom, Brazil, Argentina. 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 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.
What does the primary outcome measure?
annual rate of change in CD4 count, calculated as the slope of participants' CD4 count change / time. (time frame: up to 5 years). 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 NCT00860977, which also lists 1 linked publication.
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 6 Mar 2018; AzTrials last refreshed its copy on 1 Nov 2026.