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

NCT01432106 | Withdrawn Phase 1

• 1 other identifier: SPP100AUS20T
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; Metabolic Syndrome

Keywords

Hypertension; Metabolic Syndrome; African American

Outcome Measures

Primary Outcomes (1)

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

  2 weeks on initial dose & 6 weeks on higher dose

Study Arms (2)

Aliskiren/Valsartan (Valturna)

ACTIVE COMPARATOR

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.

Drug: Aliskerin/Valsartan and Rampiril

Ramipril

ACTIVE COMPARATOR

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.

Drug: Aliskerin/Valsartan and Rampiril

Interventions

Aliskerin/Valsartan and Rampiril DRUG

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.)

Also known as: Tekturna (Aliskerin), Diovan (Valsartan), Valturna (Aliskerin/Valsartan, Altace (Ramipril)

Aliskiren/Valsartan (Valturna); Ramipril

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Michigan Health System

Ann Arbor, Michigan, 48106, United States

Location

MeSH Terms

Conditions

Hypertension; Metabolic Syndrome

Interventions

Valsartan; aliskiren; Ramipril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Kenneth Jamerson, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 8, 2011
• First Posted: September 12, 2011
• Study Start: February 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 18, 2013

Record last verified: 2013-11

Locations

US (1)