Significance of Regional Ventriculo-arterial Coupling in Patients With Chronic Heart Failure

Heart Failure Clinical Trial

Official title:

Significance of Regional Ventriculo-arterial Coupling in Patients With Chronic Heart Failure: Effects of Endothelial Progenitor Cells and a Direct Renin Inhibitor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01298258
• Other study ID #: 99NSC-REVAC
• Status: Recruiting
• Phase: N/A
• First received: February 15, 2011
• Last updated: February 16, 2011
• Start date: July 2010
• Est. completion date: July 2013

Study information

• Verified date: July 2010
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: Chen-Huan Chen, M.D.
• Phone: 886228752973
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that the different components of arterial load are coupled with different components of LV function. The regional ventriculo-arterial couplings may be important in the pathogenesis of heart failure and ventricular remodeling, and in the prediction of future cardiovascular events.

Description:

Heart failure is a major health problem worldwide. Optimal treatment of this disabling and fatal condition may require functional characterization of the failed left ventricle (LV) and its interaction with the arterial system. Part of the physiological significance of the ventriculo-arterial coupling has been studied experimentally and clinically using the framework of the ratio of effective arterial elastance (Ea) to end-systolic elastance (Ees), with limited clinical applications.

From central ascending aorta to terminal arterioles, every segment of the arterial tree contributes to the arterial loads that interact and impact LV performance in both systole and diastole, leads to atrial and ventricular remodeling and hypertrophy, and results in the development of heart failure. On the other hand, the ventricular systole is a complex coordination of multi-directional myocardial fibers involving longitudinal contraction, circumferential shortening, radial thickening, twist, and torsion, the so-called LV deformations.

In the proposed 3-year project, the investigators hypothesize that the different components of arterial load are coupled with different components of LV function. The regional ventriculo-arterial couplings may be important in the pathogenesis of heart failure and ventricular remodeling, and in the prediction of future cardiovascular events. Therapies targeting these may play a role in the prevention and treatment of heart failure. Therefore, the investigators will study at least 60 patients with chronic heart failure (NYHA Class II-IV) who will randomly receive a direct renin inhibitor, aliskiren, or a placebo for 6 months on top of standard therapy. The purposes of the present study are to investigate the relationship between different components of hemodynamic load or arterial abnormalities and different components of LV myocardial deformations or regional LV function, the modulating effects of endothelial progenitor cells (EPCs) on the ventriculo-arterial coupling, and the therapeutic effects of aliskiren on the components of hemodynamic load and LV myocardial deformations and their couplings. The investigators will also investigate whether the ventriculo-arterial coupling, EPCs, and add-on therapy of aliskiren predict cardiovascular outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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. NT-pro BNP = 600pg/ml (BNP = 150 pg/ml) at Visit 1 or NT-pro BNP = 450 pg/mL (BNP (= 100 pg/ml) and a hospitalization for HF within last 12 months

4. Patients must be on a stable dose of either an ACE inhibitor or an ARB for at least 4 weeks prior to Visit 1.

5. 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.

6. 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 get pregnant or will be pregnant within 6 months.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Aliskiren
Aliskiren 150mg

Locations

Country	Name	City	State
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan	National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CV mortality and HF re-admission		1 year after enrollment	No
Secondary	Ventricular function		1 year after enrollment	No