Ranolazine in Diastolic Heart Failure

NCT01163734 | Completed Phase 2

• 1 other identifier: GS-US-270-0101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with CAD and clinical symptoms of heart failure or patients with suspected heart failure with preserved ejection fraction (HFpEF) will be enrolled. Study drug will be given as continuous IV infusion followed by oral treatment for 13 days. LV pressures and hemodynamic data will be measured prior to and after administration of study drug. In addition, Doppler ECHO, cardiopulmonary exercise testing (CPET), and NT-pro-BNP determination will be performed. Adverse events and safety labs will be collected and monitored.

Conditions

Diastolic Heart Failure

Keywords

Heart Failure with Preserved Ejection Fraction (HFpEF); Coronary Artery Disease (CAD)

Outcome Measures

Primary Outcomes (1)

• Change from baseline to 30 minutes in cardiac catheterization hemodynamic parameters at both resting and paced conditions

  Change from baseline to 30 minutes from initiation of study drug bolus No.1 in cardiac catheterization hemodynamic parameters at both resting and paced conditions: Time-constant of relaxation (tau) Left ventricular end-diastolic pressure (LVEDP) dP/dtmin (minimal rate of LV pressure change)

  Baseline to 30 minutes

Secondary Outcomes (3)

• Change from baseline to Day 14 in mitral E wave velocity/mitral annular velocity (E/E') ratio

  Baseline to Day 14

• Change from baseline to Day 14 in VO2 max

  Baseline to Day 14

• Change from baseline to Day 14 in N-terminal pro-brain B-type natriuretic peptide (NT-pro-BNP)

  Baseline to Day 14

Study Arms (2)

Ranolazine

EXPERIMENTAL

Drug: Ranolazine

Saline 0.9%

PLACEBO COMPARATOR

Saline 0.9% and placebo tablet

Other: Saline 0.9% and placebo tablet

Interventions

Ranolazine DRUG

Intravenous treatment followed oral treatment for 13 days.

Also known as: Ranexa

Ranolazine

Saline 0.9% and placebo tablet OTHER

Intravenous treatment followed by oral treatment for 13 days

Also known as: Normal Saline

Saline 0.9%

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged \> 40 years
• Clinical symptoms of heart failure (NYHA class II-III) at time of screening (e.g., dyspnea, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema)
• Left ventricular ejection fraction (LVEF) \> 45% at screening
• With:
• E/E' \> 15 measured by Tissue Doppler echocardiography at screening
• NT-pro-BNP \> 220pg/mL at screening
• Average resting LVEDP \>18 mm Hg (refer to continued eligibility criteria),
• Average resting time constant of relaxation (tau) \> 50 ms at time of cardiac catheterization (refer to continued eligibility criteria)
• Signed informed consent

You may not qualify if:

• Acute cardiac decompensation requiring mechanical ventilation
• Hypotension with blood pressure \< 90/50 mm Hg
• Primary hypertrophic or restrictive cardiomyopathy or systemic illness associated with infiltrative heart disease (e.g., cardiac amyloidosis)
• Pericardial constriction
• Hemodynamically significant uncorrected obstructive or regurgitant valvular disease
• Cor pulmonale or other causes of right heart failure not associated with left ventricular dysfunction
• Clinically significant pulmonary disease in the opinion of the Investigator or requiring home oxygen or oral steroid therapy
• History of serious cardiac dysrrhythmias including atrial fibrillation with resting heart rate of \> 100 beats per minute
• Need for treatment with Class I or III antiarrhythmic medications
• Implantable pacemaker, cardioverter-defibrillator, or left ventricular assist device
• Clinically significant chronic hepatic impairment (Child-Pugh Class B \[moderate\] or Class C \[severe\])
• Severe renal insufficiency defined as creatinine clearance ≤30 mL/min as calculated by Cockcroft-Gault formula or Modified Diet in Renal Disease (MDRD) equation.
• History of congenital or a family history of long QT syndrome, or known acquired QT interval prolongation
• Inability to exercise due to other co-morbidities that may affect performance of cardiopulmonary exercise test (CPET) (e.g., osteoarthritis, peripheral vascular disease)
• Current treatment with potent and moderate CYP3A inhibitors

Sponsors & Collaborators

• Gilead Sciences: lead
• University Medicine Göttingen, Cardiac Center: collaborator

Study Sites (1)

University Medicine Goettingen (UMG)

Göttingen, Germany

Location

Related Publications (2)

• Maier LS, Layug B, Karwatowska-Prokopczuk E, Belardinelli L, Lee S, Sander J, Lang C, Wachter R, Edelmann F, Hasenfuss G, Jacobshagen C. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: the RALI-DHF proof-of-concept study. JACC Heart Fail. 2013 Apr;1(2):115-22. doi: 10.1016/j.jchf.2012.12.002. Epub 2013 Apr 1.

  PMID: 24621836 DERIVED

• Jacobshagen C, Belardinelli L, Hasenfuss G, Maier LS. Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study. Clin Cardiol. 2011 Jul;34(7):426-32. doi: 10.1002/clc.20897. Epub 2011 Apr 27.

  PMID: 21538388 DERIVED

MeSH Terms

Conditions

Heart Failure, Diastolic; Coronary Artery Disease

Interventions

Ranolazine; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Lars S. Maier, MD

  University Medicine Göttingen, Cardiac Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 16, 2010
• Study Start: April 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: July 12, 2012

Record last verified: 2011-03

Locations

DE (1)