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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00902304




Registration number
NCT00902304
Ethics application status
Date submitted
28/04/2009
Date registered
14/05/2009
Date last updated
30/11/2012

Titles & IDs
Public title
Valsartan Intensified Primary Care Reduction of Blood Pressure Study
Scientific title
A Phase IV Clinical Trial of Intensified Blood Pressure Management in Primary Care Using Valsartan Alone and as Combination Anti-Hypertensive Therapy
Secondary ID [1] 0 0
CVAL489AAU01
Universal Trial Number (UTN)
Trial acronym
VIPER-BP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Valsartan and hydrochlorothiazide (HCTZ) - monotherapy
Treatment: Drugs - Valsartan and amlodipine
Treatment: Drugs - Usual care
Treatment: Drugs - Valsartan
Treatment: Drugs - Valsartan and hydrochlorothiazide (HCTZ) - combination arm

Active Comparator: Usual care - Physicians applied their usual pattern of patient visits and treatment strategies to achieve individualized blood pressure target

Experimental: Monotherapy (initial monotherapy arm) - Physicians utilized valsartan 160mg per day for 6 weeks, followed by (if required) dose titrations every 4 weeks thereafter until week 14 (valsartan 320mg per day, then valsartan 320mg plus hydrochlorothiazide (HCTZ) 12.5mg per day, then valsartan 320mg plus HCTZ 25mg per day (maximal dose)). For patients not at blood pressure target at week 18, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.

Experimental: Combination (initial combination therapy arm) - Physicians initially utilized single tablet combination products of either valsartan plus hydrochlorothiazide (HCTZ) or valsartan plus amlodipine for an initial 6 weeks of therapy (based on the treating physician's preference), with dose titrations (if required) every 4 weeks thereafter until week 10. The maximum dose for the HCTZ combination was valsartan 160mg plus HCTZ 25mg per day. The maximum dose for the amlodipine combination was valsartan 160mg plus amlodipine 10mg per day. For patients who were not at blood pressure target at week 14, physicians were requested to consider triple or alternative therapy at their own discretion for the remainder of the study.


Treatment: Drugs: Valsartan and hydrochlorothiazide (HCTZ) - monotherapy
Monotherapy arm - if monotherapy valsartan 320mg per day orally was not sufficient, then could add HCTZ up to 25 mg per day orally

Treatment: Drugs: Valsartan and amlodipine
From valsartan 80mg/amlodipine 5mg per day to valsartan 160mg/amlodipine 10mg per day orally

Treatment: Drugs: Usual care
As directed by investigator

Treatment: Drugs: Valsartan
Valsartan 160mg per day to 320mg per day orally

Treatment: Drugs: Valsartan and hydrochlorothiazide (HCTZ) - combination arm
Combination arm - from valsartan 80mg/hydrochlorothiazide 12.5mg per day to valsartan 160mg/hydrochlorothiazide 25mg per day orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Patients Who Have Achieved Their Pre-specified (Individualized National Heart Foundation of Australia Criteria) Blood Pressure (BP) Target - BP target groups were: <= 125/75mmHg, <= 130/80mmHg and <= 140/90mmHg. The BP target was based on the patient's clinical risk profile as specified by National Heart Foundation of Australia guidelines.
Timepoint [1] 0 0
26 weeks
Secondary outcome [1] 0 0
Change in Mean Sitting Systolic Blood Pressure - The visit window was from 22 to 36 weeks. If more than one blood pressure measure was available within the specified window, then the one closest to the scheduled visit was used for analysis. If no measure was available within this window, then the last recorded BP post-randomization was used for the endpoint. Analysis of covariance model was used with the factors: baseline blood pressure, treatment and blood pressure target group at randomization.
Timepoint [1] 0 0
Baseline and 26 weeks
Secondary outcome [2] 0 0
Change in Mean Sitting Diastolic Blood Pressure - The visit window was from 22 to 36 weeks. If more than one blood pressure measure was available within the specified window, then the one closest to the scheduled visit was used for analysis. If no measure was available within this window, then the last recorded BP post-randomization was used for the endpoint. Analysis of covariance model was used with the factors: baseline blood pressure, treatment and blood pressure target group at randomization.
Timepoint [2] 0 0
Baseline and 26 weeks
Secondary outcome [3] 0 0
Change in Absolute Cardiovascular Risk Score - The absolute cardiovascular risk assessment uses the Framingham Risk Equation to predict risk of a cardiovascular event over the next 5 years. A score of <10% is a low risk, 10 to 15% is a moderate risk, and >15% is a high risk.
A decrease indicates improvement.
Timepoint [3] 0 0
Baseline and 26 weeks
Secondary outcome [4] 0 0
Number of Patients With at Least One Adverse Events Attributable to Anti-hypertensive Therapy - The rate of all adverse events by preferred terms as determined by the General Practice investigators to be related to study intervention therapy was reported. Percentage of adverse events was calculated based on the number of participants analyzed. 41 adverse events were not reported as inadequate information was supplied to allow determination of drug treatment at onset.
Timepoint [4] 0 0
26 weeks
Secondary outcome [5] 0 0
Number of 'Early Responder' Patients Who Achieve Individualized Blood Pressure Control After 1 or 2 Adjustments - A comparison of the early responders was made based on the blood pressure measurements taken at the week 6 visit window according to gender and guideline targets. The guideline targets were: patients with renal impairment: 125/75 mmHg; patients with end-organ damage/cardiovascular disease: 130/80 mmHg; others: 140/90 mmHg.
Timepoint [5] 0 0
26 weeks
Secondary outcome [6] 0 0
Change in the EQ-5D Score - The EQ-5D total indexed score (AUS) measures self-reported quality of life with the following 5 dimensions: mobility (range 1,2,3), self-care (range 1,2,3), usual activity (range 1,2,3), pain/discomfort (range 1,2,3) and anxiety/depression (range 1,2,3), where a 1 indicates no problems, a 2 indicates moderate problems, and a 3 indicates severe problems. The range of possible utility scores are between -0.217 (derived from worse responses from all 5 dimensions with severe problems ie 3,3,3,3,3) and 1.000 (no problems for all 5 dimensions) for each dimension. An increase in EQ-5D indexed score (AUS) indicates improvement.
Timepoint [6] 0 0
Baseline and 26 weeks
Secondary outcome [7] 0 0
Number of Patients With Depression - Patients with depression refers to potential depressive symptoms, not clinically diagnosed depression. The 2 question Arrol screening tool was used to determine if the patient had potential depressive symptoms. The 2 questions are: During the last month have you often been bothered by feeling down, depressed or hopeless? During the past month have you often been bothered by little interest or pleasure in doing things? The presence of potential depressive symptoms was determined by a 'yes' answer to either of these questions.
Timepoint [7] 0 0
Baseline and week 26
Secondary outcome [8] 0 0
Change in Center for Epidemiologic Studies Depression (CES-D) Score From Baseline to Week 26 - The CES-D score was from 0 to 30, with a higher score indicating a higher level of depression.
The categories for the score are: 0 to 9 suggests no depression; 10 to 15 suggests mild depression; 16 to 24 suggests moderate depression; 24 or above suggests severe depression.
Timepoint [8] 0 0
Baseline and week 26
Secondary outcome [9] 0 0
Participants With End Organ Disease at Baseline and Week 26 - A patient was considered to have end organ damage with either of the following: 1) proteinuria (dipstick = 1+ or more or protein/creatinine ratio > 30mg/mol or 24h urine protein > 0.3g); 2) no proteinuria, but presence of microalbuminuria (urine albumin/creatinine ratio 3.6 to 25mg/mol(male) or 3.6 to 35mg/mol (female) detected; 3) no proteinuria or microalbuminuria, but presence of macroalbuminuria (urine albumin/creatinine ratio > 25mg/mol(male) or >35mg/mol (female) detected OR 4) ECG evidence of LVH (Sokolow-Lyon voltage criteria values >= 38mm).
Baseline potential for end organ damage was calculated in all 1562 randomised patients based on the criteria outlined above. If no investigation/data available, assumed no end-organ damage.
It is important to note that given the limited number of ECGs at 26 weeks, between group comparisons should be limited to the two time points (baseline and 26 weeks).
Timepoint [9] 0 0
Baseline and week 26
Secondary outcome [10] 0 0
Change in Self-care Behavior Score From Baseline to Week 26 - A modified self-care behavior tool (questionnaire) was used to calculate 2 domain scales: maintenance and confidence. Each domain has a standardized score between 0 and 100. Self-care is best represented by maintenance. Confidence is an important process that moderates the relationship between self-care and outcomes. Higher index score suggests better self-care. A score of 70 or greater can be used as the cut-point to judge self-care adequacy.
Timepoint [10] 0 0
Baseline and week 26
Secondary outcome [11] 0 0
Rate of Treatment Compliance - The rate of compliance was planned to be estimated from the quantity of unused medication returned at each scheduled visit over the entire follow-up period. Rate of compliance = (tablets supplied - tablets returned)/(tablets for 100% compliance).
Timepoint [11] 0 0
26 weeks
Secondary outcome [12] 0 0
Number of Patients With Major Clinical Endpoints - Major clinical endpoints measured were all-cause mortality and fatal and non-fatal cardiovascular events (e.g. acute myocardial infarction, stroke and heart failure).
Timepoint [12] 0 0
26 weeks

Eligibility
Key inclusion criteria
- newly diagnosed or currently treated hypertensive patients who have not attained their
blood pressure target and require active pharmacological treatment as recommended by
the local guidelines as judged by the general practitioner
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- significantly elevated blood pressure (severe hypertension)

- requiring 3 or more antihypertensive drugs

- severe kidney disease or dialyses

- clinical diagnosis requiring concomitant therapy with antihypertensive treatment that
would be outside the therapies allowed under study protocol

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Professor Garry Jennings-Co Principal Investigator - Melbourne
Recruitment hospital [2] 0 0
Professor Simon Stewart-Principal Investigator - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Baker IDI Heart and Diabetes Institute
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will assess the efficacy of an intensive blood pressure management strategy
compared to usual care in a primary care (general practice) setting.
Trial website
https://clinicaltrials.gov/show/NCT00902304
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications