HypertensionPhase 1SAAVENCT01432106
The Study of Novel Dual Renin Angiotensin Aldosterone System (RAAS) Blockade; Valsartan/Aliskiren in African American Patients With Hypertension and the Metabolic Syndrome
A Phase 1 study testing Aliskerin/Valsartan and Rampiril in people with Hypertension and Metabolic Syndrome, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Metabolic Syndrome
- What is being tested?
- Aliskerin/Valsartan and Rampiril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Dec 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Health System
Ann Arbor, Michigan, 48106
About this study
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 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.
Read the 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.
- Conditions
- Hypertension, Metabolic Syndrome
- Being tested
- Aliskerin/Valsartan and Rampiril
- Keywords
- Hypertension, Metabolic Syndrome, African American
- Medical subject headings
- Hypertension, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aliskerin/Valsartan and RampirilDrug
Also called Tekturna (Aliskerin), Diovan (Valsartan), Valturna (Aliskerin/Valsartan, Altace (Ramipril)
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.)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Aliskerin/Valsartan and Rampiril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in SBP from baseline to 10 weeks (2 weeks on initial dose & 6 weeks on higher dose)
Measured: 2 weeks on initial dose & 6 weeks on higher dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2011 (estimated)
- Study startFeb 2011
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: Novartis terminated all projects involving aliskiren. Findings of the DMC overseeing the ALTITUDE clinical trial found a higher incidence of adverse events.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Kenneth A. Jamerson, University of Michigan
- Investigators
- Kenneth Jamerson, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01432106
- Sponsor's protocol ID
- SPP100AUS20T
- Acronym
- SAAVE
- Status last verified
- Nov 2013
- First submitted
- 8 Sep 2011
- Last updated
- 18 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01432106
- Acronym / sponsor ID
- SAAVE / SPP100AUS20T
- Conditions
- Hypertension, Metabolic Syndrome
- Keywords
- Hypertension, Metabolic Syndrome, African American
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Novartis terminated all projects involving aliskiren. Findings of the DMC overseeing the ALTITUDE clinical trial found a higher incidence of adverse events.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Feb 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 12 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aliskiren/Valsartan (Valturna) | Active comparator | Drug: Aliskerin/Valsartan and RampirilValturna 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 | Active comparator | Drug: Aliskerin/Valsartan and RampirilRamipril (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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aliskerin/Valsartan and RampirilAlso: Tekturna (Aliskerin), Diovan (Valsartan), Valturna (Aliskerin/Valsartan, Altace (Ramipril)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.) | Drug | Aliskiren/Valsartan (Valturna), Ramipril |
Primary outcome
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Jamerson, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aliskerin/Valsartan and Rampiril in people with Hypertension and Metabolic Syndrome, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2013.