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

NCT01156207 | Unknown Phase 4

• 2 other identifiers: NSC20110101201003020MB
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

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. 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.

Conditions

Heart Failure

Keywords

To establish the coupling between components of arterial load ( and components of LV myocardial deformations at baseline and 6 months after randomization.; To establish the role of EPCs on modulation of the components of arterial load and LV myocardial deformations and their coupling.

Outcome Measures

Primary Outcomes (1)

• LV systolic function, the global longitudinal strain

  During 1-year treatment, ventricular systolic functions would be measured by using speckle tracking and presented as global longitudinal, circumferential, and radial strain at baseline and at the end of study. The changes of strain would be compared between 2 study groups.

  1 year

Secondary Outcomes (1)

• plasma NT-proBNP level

  1 year

Study Arms (2)

Aliskiren

EXPERIMENTAL

Drug: Aliskiren

placebo

PLACEBO COMPARATOR

Drug: Aliskiren

Interventions

Aliskiren DRUG

300mg Aliskiren qd for 6 month

Aliskiren; placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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
• Patients must be on a stable dose of either an ACE inhibitor or an ARB for at least 4 weeks prior to Visit 1.
• 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.
• Patients with documented sinus rhythm at Visit 1. -

You may not qualify if:

• History of hypersensitivity to any of the study drugs.
• Patients who require treatment with both ACEI and ARB.
• Current acute decompensated HF (exacerbation of chronic HF manifested by signs \& symptoms that may require IV therapy).
• Symptomatic hypotension and/or less than 100 mmHg at the time of screening or less than 90 mmHg at the time of randomization.
• 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.
• Serum potassium \> 5.0 mmol/L at screening (Visit 1).
• 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.
• Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1.
• Patients with active or unstable bronchospasm or asthma (patients must be on stable regimen of respiratory medications for 1 month prior to Visit 1).
• Right heart failure due to severe pulmonary disease.
• Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to visit 1.
• Patients with a history of heart transplant or who are on a transplant list or with left ventricular assistance device (LVAD device).
• Documented ventricular arrhythmia with syncopal episodes within past 3 months, prior to visit 1, that is untreated.
• Symptomatic bradycardia or second or third degree heart block without a pacemaker.
• Implantation of a CRT (cardiac resynchronization therapy) device within the prior 3 months from visit 1 or intent to implant a CRT device.

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead
• National Science and Technology Council, Taiwan: collaborator

Study Sites (2)

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Heart Failure

Interventions

aliskiren

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: June 6, 2010
• First Posted: July 2, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2013
• Last Updated: July 2, 2010

Record last verified: 2010-06

Locations

TW (2)