Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Aliskiren and Valsartan vs Valsartan Alone in Patients With Stage II Systolic Hypertension and Type II Diabetes Mellitus (ViVID)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00927394
First received: June 24, 2009
Last updated: December 3, 2012
Last verified: December 2012
  Purpose

The purpose of the study was to evaluate the blood pressure (BP)-lowering efficacy of the combination of aliskiren and valsartan, as initial therapy, compared to valsartan monotherapy in Type II Diabetic patients with Stage II hypertension.


Condition Intervention Phase
Hypertension
Drug: Aliskiren
Drug: Valsartan
Drug: Placebo for Aliskiren
Drug: Placebo for Valsartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: An 8 Week Randomized, Double-Blind, Parallel Group, Multi-Center, Active Controlled Study to Evaluate the Antihypertensive Efficacy and Safety of Aliskiren Administered in Combination With Valsartan Versus Valsartan Alone in Patients With Stage 2 Systolic Hypertension and Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (MASBP) at Week 8 [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    The 24-hour ambulatory systolic blood pressure was evaluated at baseline (Week 0) and post-baseline visits. The mean hourly systolic blood pressure was calculated at post-dosing hours 1-24 for each patient. The MASBP for each patient was calculated by averaging the patient's available hourly means for post-dosing hours 1-24.


Secondary Outcome Measures:
  • Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP) [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
    Sitting blood pressure was measured at trough (24 hours ± 3 hours post dose) and recorded at all study visits. At the first study visit, the arm in which the highest sitting diastolic blood pressure was found was the arm used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for five minutes, systolic and diastolic blood pressures were measured 3 times using the standard mercury sphygmomanometer. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting office blood pressure for that visit.

  • Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP) at Week 8 [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    The 24-hour ambulatory diastolic blood pressure was evaluated at baseline (Week 0) and post-baseline visits. The mean hourly diastolic blood pressure was calculated at post-dosing hours 1-24 for each patient. The MADBP for each patient was calculated by averaging the patient's available hourly means for post-dosing hours 1-24.

  • Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (MAPP) at Week 8 [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    The 24-hour ambulatory pulse pressure was evaluated at baseline (Week 0) and post-baseline visits.

  • Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP) [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
    Sitting blood pressure was measured at trough (24 hours ± 3 hours post dose) and recorded at all study visits. At the first study visit, the arm in which the highest sitting diastolic blood pressure was found was the arm used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for five minutes, systolic and diastolic blood pressures were measured 3 times using the standard mercury sphygmomanometer. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting office blood pressure for that visit.

  • Change From Baseline in Mean Sitting Pulse Pressure (MSPP) at Week 8 [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    At each visit, the pulse rate was measured for 30 seconds just prior to the first sitting blood pressure measurement.

  • Percentage of Patients Achieving Blood Pressure Control [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Blood pressure control was defined as MSSBP/MSDBP <140/90 mmHg. Percentage of patients achieving of blood pressure control at the corresponding visit was reported

  • Percentage of Responders [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    Responders were defined as patients with MSSBP <130 mmHg or a reduction from baseline in MSSBP of >20 mmHg.Percentage of responders achieving a response at the corresponding visit was reported.

  • Change From Baseline in Plasma Renin Activity (PRA) at Week 8 [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
  • Change From Baseline in Plasma Renin Concentration (PRC) at Week 8 [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
  • Change From Baseline in Plasma Aldosterone at Week 8 [ Time Frame: Baseline, week 8 ] [ Designated as safety issue: No ]
  • Number of Patients With Adverse Events, Serious Adverse Events and Death [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen.

    Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.



Enrollment: 1143
Study Start Date: May 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Therapy: Aliskiren + Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day)for 8 weeks. 1 tablet of Aliskiren 150 mg + 1 tablet of placebo Aliskiren 150 mg + 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg daily for 2 weeks. Forced titrated to: 2 tablets of Aliskiren 150 mg + 2 capsules of Valsartan 160 mg daily for 6 weeks
Drug: Aliskiren
Aliskiren 150 mg tablet
Drug: Valsartan
Valsartan 160 mg capsules
Drug: Placebo for Aliskiren
Placebo for Aliskiren 150 mg tablets
Drug: Placebo for Valsartan
Placebo for Valsartan 160 mg capsules
Active Comparator: Monotherapy: Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day) for 8 weeks. 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 2 weeks. Forced titrated to: 2 capsules of Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 6 weeks.
Drug: Valsartan
Valsartan 160 mg capsules
Drug: Placebo for Aliskiren
Placebo for Aliskiren 150 mg tablets
Drug: Placebo for Valsartan
Placebo for Valsartan 160 mg capsules

Detailed Description:

When protocol Amendment 2 was released, there were patients who had already been randomized into the study. These patients were included in the trial prior to making changes to the eligibility criteria. Thus, the study contains 2 distinct cohorts. Cohort 1 contains those patients who had already been randomized, and had been deemed eligible based on the original inclusion/exclusion criteria, prior to Amendment 2. No new patients were randomized to Cohort 1. Cohort 2 contains patients who were randomized, having been found eligible based on the revised inclusion/exclusion criteria, after Amendment 2. Differences in the inclusion and exclusion criteria are indicated below.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed.
  • Men or women 18 years and older.
  • Patients with Type 2 diabetes mellitus with an HbA1c ≤ 9 % at visit 1 and on a stable anti-diabetic regimen not including insulin or stable diet and exercise for at least 4 weeks prior to visit 1.

Cohort 1:

  • Patients with Stage 2 systolic hypertension, defined as having a MSSBP ≥160 mmHg and <200 mmHg at Visit 5 (randomization).
  • Patients who have been newly diagnosed with hypertension or who have not received antihypertensive medication for at least 4 weeks (28 days) prior to Visit 1 must have MSSBP ≥ 160 mmHg and < 200 mmHg at Visit 1, otherwise, they will be considered screen failures.
  • Patients receiving antihypertensive medication must have a MSSBP of ≥150 mmHg and <200 mmHg at Study Visit 1, otherwise they will be considered screen failures.

Cohort 2:

  • Patients must also have had a mean 8-hour daytime ambulatory systolic blood pressure (ASBP) ≥140 mmHg AND mean 8-hour daytime ambulatory diastolic blood pressure (ADBP) ≥90 mmHg at Visit 5 (randomization).
  • Hypertensive patients with MSSBP ≥150 mmHg and but <200 mmHg AND MSDBP ≥95 but <120 mmHg at Visit 5 (randomization).
  • Patients who had been newly diagnosed with hypertension or who had not received antihypertensive medication for at least 4 weeks (28 days) prior to Visit 1 must have had MSSBP ≥150 mmHg but <200 mmHg and MSDBP ≥95 but <120 mmHg at Visit 1, otherwise, they were considered screen failures.

Exclusion Criteria:

  • Office blood pressure measured by cuff (MSSBP ≥200 mmHg or MSDBP ≥120 mmHg).
  • History or evidence of secondary hypertension of any etiology.
  • Refractory hypertension, defined as having uncontrolled BP (≥140/90 mmHg) while receiving 3 antihypertensive medications at the maximum approved dose of each drug, one of which must be a diuretic.
  • Patients treated with more than 3 antihypertensive medications (each component of a combination drug counts individually).
  • Type 2 diabetes mellitus currently requiring insulin treatment.
  • modification of diet in renal disease (MDRD) estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2
  • Serum sodium less than lower limit of normal, serum potassium < 3.5 mEq/L or ≥ 5.3 mEq/L at Visit 1.
  • Known Keith-Wagener grade III or IV hypertensive retinopathy.

Cohort 1:

- Patients with known diabetic retinopathy (eg, having a history of laser therapy for diabetic retinopathy) or diabetic neuropathy (eg, receiving medication for diabetic neuropathy).

Cohort 2:

- Patients with known diabetic retinopathy or diabetic neuropathy and/or having a history of treatment for either.

Other protocol-defined inclusion/exclusion criteria applied.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00927394

Locations
United States, Delaware
Investigative Site
Newark, Delaware, United States, USA
United States, Missouri
Investigative Site
Kansas, Missouri, United States
United States, New Jersey
Investigative Site
Camden, New Jersey, United States
United States, Pennsylvania
Investigative Site
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Novartis
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00927394     History of Changes
Other Study ID Numbers: CSPV100AUS02
Study First Received: June 24, 2009
Results First Received: October 1, 2012
Last Updated: December 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Hypertension, Type II Diabetes, Aliskiren, Valsartan,
Systolic blood pressure, Diastolic blood pressure,
Stage II, Combination

Additional relevant MeSH terms:
Diabetes Mellitus
Hypertension
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014