Ranolazine in Diastolic Heart Failure (RALI-DHF)

This study has been completed.
Sponsor:
Collaborator:
University Medicine Göttingen, Cardiac Center
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01163734
First received: July 12, 2010
Last updated: July 11, 2012
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Diastolic Heart Failure
Drug: Ranolazine
Other: Saline 0.9% and placebo tablet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: A Randomized, Double-blind, Placebo-controlled Study of Ranolazine in Patients With Heart Failure With Preserved Ejection Fraction

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change from baseline to 30 minutes in cardiac catheterization hemodynamic parameters at both resting and paced conditions [ Time Frame: Baseline to 30 minutes ] [ Designated as safety issue: No ]

    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)



Secondary Outcome Measures:
  • Change from baseline to Day 14 in mitral E wave velocity/mitral annular velocity (E/E') ratio [ Time Frame: Baseline to Day 14 ] [ Designated as safety issue: No ]
  • Change from baseline to Day 14 in VO2 max [ Time Frame: Baseline to Day 14 ] [ Designated as safety issue: No ]
  • Change from baseline to Day 14 in N-terminal pro-brain B-type natriuretic peptide (NT-pro-BNP) [ Time Frame: Baseline to Day 14 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: April 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine Drug: Ranolazine
Intravenous treatment followed oral treatment for 13 days.
Other Name: Ranexa
Placebo Comparator: Saline 0.9%
Saline 0.9% and placebo tablet
Other: Saline 0.9% and placebo tablet
Intravenous treatment followed by oral treatment for 13 days
Other Name: Normal Saline

Detailed Description:

This is a randomized, double-blind, placebo-controlled proof-of-concept study of ranolazine in patients with heart failure with preserved ejection fraction (HFpEF). Patients will be randomized to receive ranolazine or placebo in a 1.5:1 ratio (12 ranolazine: 8 placebo).

Treatment will consist of intravenous infusion of study drug followed by oral treatment for a total of 14 days treatment period. Study contact will be made approximately 14 days after the treatment period to assess safety.

Cardiac catheterization will be performed for LV pressures and hemodynamic measurements before and after drug administration. Doppler ECHO, CPET, and NT-pro-BNP determination will be performed at screening and at end of study. Adverse events and safety labs will be monitored and collected.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females aged > 40 years
  2. Clinical symptoms of heart failure (NYHA class II-III) at time of screening (e.g., dyspnea, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema)
  3. Left ventricular ejection fraction (LVEF) > 45% at screening
  4. 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)
  5. Signed informed consent

Exclusion Criteria:

  1. Acute cardiac decompensation requiring mechanical ventilation
  2. Hypotension with blood pressure < 90/50 mm Hg
  3. Primary hypertrophic or restrictive cardiomyopathy or systemic illness associated with infiltrative heart disease (e.g., cardiac amyloidosis)
  4. Pericardial constriction
  5. Hemodynamically significant uncorrected obstructive or regurgitant valvular disease
  6. Cor pulmonale or other causes of right heart failure not associated with left ventricular dysfunction
  7. Clinically significant pulmonary disease in the opinion of the Investigator or requiring home oxygen or oral steroid therapy
  8. History of serious cardiac dysrrhythmias including atrial fibrillation with resting heart rate of > 100 beats per minute
  9. Need for treatment with Class I or III antiarrhythmic medications
  10. Implantable pacemaker, cardioverter-defibrillator, or left ventricular assist device
  11. Clinically significant chronic hepatic impairment (Child-Pugh Class B [moderate] or Class C [severe])
  12. Severe renal insufficiency defined as creatinine clearance ≤30 mL/min as calculated by Cockcroft-Gault formula or Modified Diet in Renal Disease (MDRD) equation.
  13. History of congenital or a family history of long QT syndrome, or known acquired QT interval prolongation
  14. Inability to exercise due to other co-morbidities that may affect performance of cardiopulmonary exercise test (CPET) (e.g., osteoarthritis, peripheral vascular disease)
  15. Current treatment with potent and moderate CYP3A inhibitors
  16. Current treatment with potent CYP3A inducers (e.g., rifampin/rifampicin, St. John's Wort, carbamazepin/carbamazepine)
  17. Prior treatment with ranolazine
  18. Other conditions that in the opinion of the investigator may increase the risk to the patient (e.g. pts with weight ≤60 kg), prevent compliance with study protocol or compromise the quality of the clinical trial

Continued Eligibility Criteria:

Patients must continue to meet eligibility criteria and have an average (of 3 measurements) resting LVEDP > 18 mm Hg and resting tau > 50 ms at time of cardiac catheterization to receive study drug.

  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: NCT01163734

Locations
Germany
University Medicine Goettingen (UMG)
Goettingen, Germany
Sponsors and Collaborators
Gilead Sciences
University Medicine Göttingen, Cardiac Center
Investigators
Principal Investigator: Lars S. Maier, MD University Medicine Göttingen, Cardiac Center
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01163734     History of Changes
Other Study ID Numbers: GS-US-270-0101
Study First Received: July 12, 2010
Last Updated: July 11, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Gilead Sciences:
Heart Failure with Preserved Ejection Fraction (HFpEF)
Coronary Artery Disease (CAD)

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014