Ranolazine in Diastolic Heart Failure

Diastolic Heart Failure Clinical Trial

— RALI-DHF  

Official title:

A Randomized, Double-blind, Placebo-controlled Study of Ranolazine in Patients With Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01163734
• Other study ID #: GS-US-270-0101
• Status: Completed
• Phase: Phase 2
• First received: July 12, 2010
• Last updated: July 11, 2012
• Start date: April 2010
• Est. completion date: February 2011

Study information

• Verified date: March 2011
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Diastolic Heart Failure
• Heart Failure
• Heart Failure, Diastolic

Intervention

Drug:
• Ranolazine
Intravenous treatment followed oral treatment for 13 days.

Other:
• Saline 0.9% and placebo tablet
Intravenous treatment followed by oral treatment for 13 days

Locations

Country	Name	City	State
Germany	University Medicine Goettingen (UMG)	Goettingen

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	University Medicine Göttingen, Cardiac Center

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change from baseline to Day 14 in mitral E wave velocity/mitral annular velocity (E/E') ratio		Baseline to Day 14	No
Secondary	Change from baseline to Day 14 in VO2 max		Baseline to Day 14	No
Secondary	Change from baseline to Day 14 in N-terminal pro-brain B-type natriuretic peptide (NT-pro-BNP)		Baseline to Day 14	No