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The Study of Novel Dual Renin Angiotensin Aldosterone System (RAAS) Blockade; Valsartan/Aliskiren in African American Patients With Hypertension and the Metabolic Syndrome (SAAVE)

Primary Purpose

Hypertension, Metabolic Syndrome

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Aliskerin/Valsartan and Rampiril

About this trial

This is an interventional treatment trial for Hypertension focused on measuring Hypertension, Metabolic Syndrome, African American

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

African American men or women 18 - 80 years of age.
Appropriate therapy for high blood pressure consisting of no more than 2 antihypertensives.
Patients with at least one marker of Metabolic Syndrome as evidenced by:
- HDL cholesterol < 35mg/dl (men); < 45 mg/dl (women)
- Triglycerides > 200mg/dl
- Fasting Glucose >100mg/dl
- Waist Circumference: Men >40 inches (102cm); Women > 35 (88cm)
Recent copy of EKG.
Women able to become pregnant must use reliable contraception (e.g. hormonal contraception and double-barrier methods) throughout this study and for one week after the end of this study. Post-menopausal or surgically sterile women.

Exclusion Criteria:

Uncontrolled hypertension.
Organ transplant.
Hypersensitivity to any study medications
Systolic pressure 170 or higher or Diastolic pressure 110 or higher.
Cardiovascular events within last 6 months Stroke, Heart Attack, Stent, or Hospitalization for severe Heart Failure.
Serum potassium greater than 5.0
Heart block without a pacemaker, continuing arrhythmia or valvular heart disease.
Blocked renal artery.
Patients with severe renal impairment (creatinine 1.7 mg/dl for women and 2.0 mg/dl for men and or estimated GFR <30 mL/min) a history of dialysis, nephritic syndrome, or reno-vascular hypertension.
Any condition that may alter medication absorption.
Any condition that may place patient at higher risk from participating in study or will jeopardize the evaluation of efficacy or safety.
Use of any investigational study medications within 30 days of enrollment
Persons unwilling or unable to take regular medications or comply with study protocol.
Pregnant or nursing (lactating) women, or women of childbearing potential (defined as all women physiologically capable of becoming pregnant) who do not use reliable methods of contraception: surgical sterilization, bilateral tubal ligation, hormonal contraception, implantable and oral) and double barrier methods if accepted by local regulatory authority and ethics committee. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation.

Sites / Locations

University of Michigan Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Aliskiren/Valsartan (Valturna)

Ramipril

Arm Description

Valturna contains two prescription medicines in one tablet that work together to lower blood pressure. It contains aliskerin (Tekturna), a direct rennin inhibitor (DRI), and valsartan (Diovan), an angiotensin II receptor blocker (ARB). Aliskerin reduces the effect of rennin, and the harmful process that narrows blood vessels. It also helps blood vessels relax and widen so blood pressure is lower. Valsartan can help lower blood pressure by blocking a potent chemical, angiotensin II, which leads to blood vessel constriction and narrowing.

Ramipril (Altace) is an angiotensin-converting enzyme inhibitor (ACEI). It is a chemical compound that helps create a protein named angiotensin II. Angiotensin II can raise blood pressure by causing your blood vessels to narrow. Altace helps lower blood pressure by decreasing the amount of ACE the body makes. Ramipril has been proven by the investigators to stabilize decline in kidney function in African American patients with evidence of damage.

Outcomes

Primary Outcome Measures

Mean Change in SBP from baseline to 10 weeks (2 weeks on initial dose & 6 weeks on higher dose)

Secondary Outcome Measures

Full Information

NCT ID

NCT01432106

First Posted

September 8, 2011

Last Updated

November 14, 2013

Sponsor

University of Michigan

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01432106

Brief Title

The Study of Novel Dual Renin Angiotensin Aldosterone System (RAAS) Blockade; Valsartan/Aliskiren in African American Patients With Hypertension and the Metabolic Syndrome

Acronym

SAAVE

Official Title

A Randomized, Double Blind, Active Comparator, Parallel-group Study to Determine Whether the Combination of Valsartan and Aliskiren Provides Cardioprotection in African American Patients With Hypertension and Elements of the Metabolic Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Withdrawn

Why Stopped

Novartis terminated all projects involving aliskiren. Findings of the DMC overseeing the ALTITUDE clinical trial found a higher incidence of adverse events.

Study Start Date

February 2011 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Michigan

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Study purpose: African Americans with hypertension and markers of metabolic syndrome (small elevations in blood glucose, triglycerides and or weight) are at a high risk of cardiovascular (heart and blood vessel) problems. There is a circulating factor called angiotensin II that increases risk and may be more important in African Americans who have up to 20 times greater risk of losing kidney function and requiring dialysis. Research Investigators, including those at the University of Michigan, found one drug (Ramipril) that blocks angiotensin II effects significantly and improves kidney function in African Americans. The purpose of The SAAVE Study is to determine whether the combination of two new blockers (Valsartan and Aliskiren) of angiotensin II, are better able to lower blood pressure, also improve some of the risk factors for cardiovascular problems and provide greater protection to the heart and kidneys.

Detailed Description

The specific hypothesis of this proposal is that the combination of Valsartan/Aliskiren will provide incremental reduction in blood pressure when compared to traditional blockade of Renin Angiotensin Aldosterone System (RAAS) with ramipril. As an exploratory analysis, we propose that the blood pressure effect will be associated with suppressing plasma aldosterone levels, preserving the availability of nitric oxide, and preventing the development of insulin resistance. Other variables of interest include changes from baseline in adiponectin, Procollagen 1 and 3, osteopontin, cystatin C, and serum K+. In a nested cohort we will determine the impact of novel dual RAAS blockade on left ventricular remodeling. Should our hypotheses be proven correct and novel dual RAAS blockade is more effective than ramipril in reducing blood pressure, plasma aldosterone, preserving the availability of nitric oxide, as reflected by an increase in asymmetric dimethly arginine (ADMA) levels, and improves cardiovascular remodeling, this would have important implications for the long term prevention of target organ damage and cardiovascular events in this high risk ethnic group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension, Metabolic Syndrome

Keywords

Hypertension, Metabolic Syndrome, African American

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Aliskiren/Valsartan (Valturna)

Arm Type

Active Comparator

Arm Description

Arm Title

Ramipril

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Aliskerin/Valsartan and Rampiril

Other Intervention Name(s)

Tekturna (Aliskerin), Diovan (Valsartan), Valturna (Aliskerin/Valsartan, Altace (Ramipril)

Intervention Description

Patients will start on low dose Ramipril 10 mg or Valturna 150/160 at visit 2, and up-titrate to target dose of Ramipril 20 mg or Valturna 300/320 at visit 3. At visit 5, the addition of Hydrochlorothiazide (HCTZ) or amlodipine will be allowed to achieve the SBP target of < 140 mmHg. High dose will then be maintained throughout the remainder of the study. In case of symptoms of low blood pressures, the study medication may be decreased to the low dose. (However, all non-study medication will be manipulated, initially.)

Primary Outcome Measure Information:

Title

Mean Change in SBP from baseline to 10 weeks (2 weeks on initial dose & 6 weeks on higher dose)

Time Frame

2 weeks on initial dose & 6 weeks on higher dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: African American men or women 18 - 80 years of age. Appropriate therapy for high blood pressure consisting of no more than 2 antihypertensives. Patients with at least one marker of Metabolic Syndrome as evidenced by: HDL cholesterol < 35mg/dl (men); < 45 mg/dl (women) Triglycerides > 200mg/dl Fasting Glucose >100mg/dl Waist Circumference: Men >40 inches (102cm); Women > 35 (88cm) Recent copy of EKG. Women able to become pregnant must use reliable contraception (e.g. hormonal contraception and double-barrier methods) throughout this study and for one week after the end of this study. Post-menopausal or surgically sterile women. Exclusion Criteria: Uncontrolled hypertension. Organ transplant. Hypersensitivity to any study medications Systolic pressure 170 or higher or Diastolic pressure 110 or higher. Cardiovascular events within last 6 months Stroke, Heart Attack, Stent, or Hospitalization for severe Heart Failure. Serum potassium greater than 5.0 Heart block without a pacemaker, continuing arrhythmia or valvular heart disease. Blocked renal artery. Patients with severe renal impairment (creatinine 1.7 mg/dl for women and 2.0 mg/dl for men and or estimated GFR <30 mL/min) a history of dialysis, nephritic syndrome, or reno-vascular hypertension. Any condition that may alter medication absorption. Any condition that may place patient at higher risk from participating in study or will jeopardize the evaluation of efficacy or safety. Use of any investigational study medications within 30 days of enrollment Persons unwilling or unable to take regular medications or comply with study protocol. Pregnant or nursing (lactating) women, or women of childbearing potential (defined as all women physiologically capable of becoming pregnant) who do not use reliable methods of contraception: surgical sterilization, bilateral tubal ligation, hormonal contraception, implantable and oral) and double barrier methods if accepted by local regulatory authority and ethics committee. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kenneth Jamerson, MD

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Health System

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48106

Country

United States

12. IPD Sharing Statement

Learn more about this trial

The Study of Novel Dual Renin Angiotensin Aldosterone System (RAAS) Blockade; Valsartan/Aliskiren in African American Patients With Hypertension and the Metabolic Syndrome

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