Add-on Aliskiren Treatment in Patients With Chronic Congestive Heart Failure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2009 by National Taiwan University Hospital.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Taipei Veterans General Hospital, Taiwan
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01040494
First received: December 25, 2009
Last updated: January 18, 2010
Last verified: December 2009
  Purpose

Aliskiren is a potent direct renin inhibitor and has been recently shown to have favorable neurohumoral effects in patients with heart failure (HF) Objective:To study the effects of add-on aliskiren treatment in patients with HF on components of arterial load, from central aorta to peripheral arterioles and biomarkers Methods:Patients with NYHA Class II to IV HF, who have been treated with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker are randomized to 6 months of treatment with placebo or aliskiren (150mg per day) treatment. Components of arterial load, from central aorta to peripheral arterioles as well as a wide-range of biomarkers, including inflammatory biomarkers, N-terminal pro-B type natriuretic peptide, arterial remodeling markers (procollagen, matrix metalloproteinase) will be measured before, 2 months and 6 months after treatment.

What is New or Innovative in this study? The importance of central hemodynamics and biomarker changes in patients with HF has been shown in observation studies. This is the first randomized control trial that examines comprehensively the effects of a direct rennin inhibitor on central hemodynamics and biomarkers in HF patients who are receiving standard heart failure therapy.


Condition Intervention Phase
Congestive Heart Failure
Drug: Aliskiren
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of add-on Aliskiren Treatment on Central and Peripheral Hemodynamics and Biomarkers in Patients With Chronic Congestive Heart Failure (NYHA Class II-IV) (First Year Project)

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Central hemodynamics including aortic impedance, central blood pressure, pulse wave velocity [ Time Frame: baseline, 2 months, 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biomarkers including NT-pro-BNP, CRP, MMP [ Time Frame: baseline, 2 months, 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2010
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aliskiren, add-on
HF patients will be randomized to receive add-on aliskiren 150 mg for 6 months
Drug: Aliskiren
all eligible patients will be randomized to receive aliskiren 150 mg on top of optimal HF therapy, including ACEI, ARB, beta blockers as considered appropriate by the investigator and in accordance with standard therapy guidelines for 6 months
Other Name: rasilez
Placebo Comparator: placebo, add-on
patients will be randomized to receive add-on placebo for 6 months
Drug: Placebo
all eligible patients will be randomized to receive placebo on top of optimal HF therapy, including ACEI, ARB, beta blockers as considered appropriate by the investigator and in accordance with standard therapy guidelines for 6 months
Other Name: Placebo

Detailed Description:

Introduction: Aliskiren is a potent direct renin inhibitor and has been recently shown to have favorable neurohumoral effects in patients with heart failure (HF) Objective:To study the effects of add-on aliskiren treatment in patients with HF on components of arterial load, from central aorta to peripheral arterioles and biomarkers Methods:Patients with NYHA Class II to IV HF, who have been treated with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker are randomized to 6 months of treatment with placebo or aliskiren (150mg per day) treatment. Components of arterial load, from central aorta to peripheral arterioles as well as a wide-range of biomarkers, including inflammatory biomarkers, N-terminal pro-B type natriuretic peptide, arterial remodeling markers (procollagen, matrix metalloproteinase) will be measured before, 2 months and 6 months after treatment.

What is New or Innovative in this study? The importance of central hemodynamics and biomarker changes in patients with HF has been shown in observation studies. This is the first randomized control trial that examines comprehensively the effects of a direct rennin inhibitor on central hemodynamics and biomarkers in HF patients who are receiving standard heart failure therapy.

  Eligibility

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

Inclusion Criteria:

  1. Outpatients ≥ 18 years of age, male or female. Female patients must be either post-menopausal for one year, surgically sterile, or using effective contraceptive methods such as oral contraceptives, barrier method with spermicide or an intrauterine device.
  2. Patients with a diagnosis of chronic heart failure (NYHA Class II-IV) and reduced systolic function: LVEF ≤ 45% at Visit 1 (local measurement, measured within the past 6 months assessed by echocardiogram, MUGA, CT scan, MRI or ventricular angiography).
  3. Patients must be on a stable dose of either an ACE inhibitor or an ARB for at least 4 weeks prior to Visit 1.
  4. Patients must be treated with a beta blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks prior to Visit 1.
  5. Patients with documented sinus rhythm at Visit 1.

Exclusion Criteria:

  1. History of hypersensitivity to any of the study drugs.
  2. Patients who require treatment with both ACEI and ARB.
  3. Current acute decompensated HF (exacerbation of chronic HF manifested by signs & symptoms that may require IV therapy).
  4. Symptomatic hypotension and/or less than 100 mmHg at the time of screening or less than 90 mmHg at the time of randomization.
  5. eGFR < 30 ml/min/1.73m2 as measured by the MDRD formula at Visit 1 (screening) , or a > 25% decrease after 14 days of active run-in period.
  6. Serum potassium > 5.0 mmol/L at screening (Visit 1).
  7. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months prior to visit 1.
  8. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1.
  9. Patients with active or unstable bronchospasm or asthma (patients must be on stable regimen of respiratory medications for 1 month prior to Visit 1).
  10. Right heart failure due to severe pulmonary disease.
  11. Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 1.
  12. Patients with a history of heart transplant or who are on a transplant list or with left ventricular assistance device (LVAD device).
  13. Documented ventricular arrhythmia with syncopal episodes within past 3 months, prior to visit 1, that is untreated.
  14. Symptomatic bradycardia or second or third degree heart block without a pacemaker.
  15. Implantation of a CRT (cardiac resynchronization therapy) device within the prior 3 months from visit 1 or intent to implant a CRT device.
  16. Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
  17. Presence of other hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic and sub-aortic stenosis.
  18. Severe primary pulmonary, renal or hepatic disease.
  19. Presence of any other disease with a life expectancy of < 1 year.
  20. Chronic long-term requirement for NSAIDs (high dose) or COX2 inhibitors, with the exception of aspirin at doses used for CV prophylaxis (≤325 mg o.d.).
  21. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs
  22. Subjects are now breast feeding, get pregnant or will be pregnant within 6 months.
  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: NCT01040494

Contacts
Contact: Lian-YU Lin, MD, PhD 886-2-23123456 ext 65002 lin7010@ms1.hinet.net

Locations
Taiwan
National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 886
Contact: Lian-Yu Lin, MD, PhD    +886-2-23123456 ext 65002    lin7010@ms1.hinet.net   
Principal Investigator: Lian-Yu Lin, MD, PhD         
Taipei Veteral General Hospital Not yet recruiting
Taipei, Taiwan, 886
Contact: Chen-Huan Chen, MD, PhD    +886-2-8712121 ext 2073    chench@vghtpe.gov.tw   
Principal Investigator: Chen-Huan Chen, MD, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
Taipei Veterans General Hospital, Taiwan
Investigators
Principal Investigator: Lian-Yu Lin, MD, PhD National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: Lian-Yu Lin, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01040494     History of Changes
Other Study ID Numbers: 200911004M
Study First Received: December 25, 2009
Last Updated: January 18, 2010
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Aliskiren
Congestive heart failure
Central hemodynamics

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 19, 2014