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

July 12, 2010
July 11, 2012
April 2010
February 2011   (final data collection date for primary outcome measure)
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)

Same as current
Complete list of historical versions of study NCT01163734 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Ranolazine in Diastolic Heart Failure
A Randomized, Double-blind, Placebo-controlled Study of Ranolazine in Patients With Heart Failure With Preserved Ejection Fraction

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Diastolic Heart Failure
  • Drug: Ranolazine
    Intravenous treatment followed oral treatment for 13 days.
    Other Name: Ranexa
  • Other: Saline 0.9% and placebo tablet
    Intravenous treatment followed by oral treatment for 13 days
    Other Name: Normal Saline
  • Experimental: Ranolazine
    Intervention: Drug: Ranolazine
  • Placebo Comparator: Saline 0.9%
    Saline 0.9% and placebo tablet
    Intervention: Other: Saline 0.9% and placebo tablet
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
February 2011
February 2011   (final data collection date for primary outcome measure)

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.

Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01163734
GS-US-270-0101
No
Gilead Sciences
Gilead Sciences
University Medicine Göttingen, Cardiac Center
Principal Investigator: Lars S. Maier, MD University Medicine Göttingen, Cardiac Center
Gilead Sciences
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP