Contact information
Type
Scientific
Primary contact
Dr Sharon Walmsley
ORCID ID
Contact details
Toronto General Hospital
200 Elizabeth Street
13EN Room 218
Toronto
Ontario
M5G 2C4
Canada
+1 416 340 3871
sharon.walmsley@uhn.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00860977
Protocol/serial number
MCT-94245
Study information
Scientific title
Valaciclovir in delaying antiretroviral treatment entry: a multicentre, randomised, placebo-controlled, fully blinded clinical trial
Acronym
VALIDATE
Study hypothesis
As or 17-12-2012, the title changed to “Can Valaciclovir delay the need for initiation of human immunodeficiency virus (HIV) treatment in HIV – infected individuals”
As of 10/09/2010 a rollover (off treatment) period was added and the overall trial end date was updated to 01/03/2016
As of 21/09/2015 the overall trial end date has been updated from 01/03/2015 to 30/09/2016 and the recruitment end date has been updated from 01/03/2015 to 11/08/2015.
As of 09/03/2010 this trial has now started to actively recruit participants. The anticipated trial dates of this record have been updated to reflect this; all changes can be found in the relevant fields. The previous anticipated start and end dates were as follows:
Previous anticipated start date: 31/10/2009
Previous anticipated end date: 31/10/2015
As of 18/08/2009 this record has been extensively updated; all updates can be found under the relevant field with the above update date. Please also note that at this time, the anticipated start and end dates of this trial have also been updated; the initial anticipated start and end dates were:
Initial anticipated start date: 01/05/2009
Initial anticipated end date: 30/04/2015
At this time, Argentina was also added as a country of recruitment, and the Sponsor was updated (initial sponsor at the time of registration was Canadian HIV Trials Network (CTN) (Canada)).
Current hypothesis as of 18/08/2009:
Valaciclovir 500 mg orally twice daily delays the time until highly active anti-retroviral therapy (HAART) is recommended or initiated among adults with both stable untreated human immunodeficiency virus (HIV) and herpes simplex virus (HSV) type 2 co-infection.
Initial hypothesis at the time of registration:
Valaciclovir 500 mg orally twice daily delays the time until highly active anti-retroviral therapy (HAART) is recommended or initiated among adults with both stable untreated human immunodeficiency virus (HIV) and infrequent or asymptomatic herpes simplex virus (HSV) type 2 co-infection.
Ethics approval
Added 09/03/2010:
University Health Network Research Ethics Board approved on the 22nd September 2009.
Study design
Multicentre randomised placebo-controlled fully blinded clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) co-infection
Intervention
Patients in the intervention group will receive oral valaciclovir 500 mg twice daily, the standard dose used for HSV-2 suppression in HIV-infected individuals. Individuals in the control arm will receive an odourless placebo tablet identical to valacyclovir in appearance and taste, to be taken twice daily.
The anticipated duration of follow-up for both arms of the trial is 3 - 5 years.
Intervention type
Drug
Phase
Phase IV
Drug names
Valaciclovir
Primary outcome measure
As or 17/12/2012 primary outcome changed to: Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change/time.
Initial primary outcome measure:
Time from baseline until reaching the primary endpoint: a composite of either a CD4 cell count less than or equal to 350 cells/mm^3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
Secondary outcome measures
1. Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change/time
2. Annual rate of change in the CD4 cell count percentage, calculated as the slope of the patient's CD4 count percentage change over time
3. Log^10 plasma HIV viral load at 12, 24 and 36 months of follow-up
4. Treatment-emergent adverse events and laboratory abnormalities (complete blood count [CBC], plasma creatinine, blood urea nitrogen, alanine transaminase, aspartate transaminase, total bilirubin, amylase, international normalised ratio, partial thromboplastin time)
5. Frequency of episodes of HSV reactivations at any anatomic site
6. Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed aciclovir-resistant HSV
Added 18/08/2009:
7. Quality of life
As of 17/12/2012 the first secondary outcome changed to: Time from baseline until reaching the primary endpoint: a composite of either a CD4 cell count less than or equal to 350 cells/mm^3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first.
Overall trial start date
01/03/2010
Overall trial end date
01/03/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 17/12/2012:
1. Adult (aged 18 years or older or as per Local/Provincial Guidelines), either sex, with documented HIV-1 infection
2. Documented HIV-1 infection (determined by EIA and Western blot)
3. No use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
4. Anti-retroviral naive (no more than 14 days of total prior anti-retroviral [ARV] exposure)
5. 5. 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)
6. Does not meet recommendations for initiating ARV therapy according to current guidelines
Initial inclusion criteria at the time of registration:
1. Adults aged over 18 years, either sex, with documented HIV-1 infection
2. Documented HSV-2 seropositivity
3. Maximum of two episodes recurrent symptomatic HSV recurrences per year by self-report
4. Neither currently using nor anticipated to require chronic anti-HSV therapy during the study
5. Anti-retroviral naive (no more than 14 days of total prior anti-retroviral [ARV] exposure)
6. CD4 count within the 400 - 900 cells/mm^3 range (inclusive) on two consecutive occasions, with at least one measurement within 4 weeks of initiating trial
7. Does not meet recommendations for initiating ARV therapy according to current guidelines
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
230
Participant exclusion criteria
Current exclusion criteria as of 17/12/2012:
1. Pregnant or actively planning to become pregnant
2. Receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
3. Have an estimated creatinine clearance less than 30 ml/min
4. Have another medical condition likely to cause death within 24 months
5. Enrolled in a therapeutic HIV vaccine or immunotherapy trial
6. Enrolled in another trial investigating the impact of another intervention on HIV disease progression
7. 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
Initial exclusion criteria at the time of registration:
1. Pregnant
2. Receiving chemotherapy or chronic steroid therapy
3. Have an estimated creatinine clearance less than 30 ml/min
4. Have an active opportunistic infection
5. Have another medical condition likely to cause death within 24 months
6. Enrolled in a therapeutic vaccine or immunotherapy trial
7. Enrolled in another trial investigating the impact of another intervention on HIV disease progression
8. Fit the phenotype of an HIV elite controller (EC), since the natural history of HIV infection is fundamentally different in such individuals
Recruitment start date
01/03/2010
Recruitment end date
11/08/2015
Locations
Countries of recruitment
Argentina, Brazil, Canada
Trial participating centre
Toronto General Hospital
Toronto, Ontario
M5G 2C4
Canada
Sponsor information
Organisation
University Health Network (UHN) (Canada)
Sponsor details
200 Elizabeth Street
Toronto
Ontario
M5G 2C4
Canada
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-94245)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2010 protocol in http://www.ncbi.nlm.nih.gov/pubmed/21106086
Publication citations
-
Protocol
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, 11, 113, doi: 10.1186/1745-6215-11-113.