Ranolazine in Diastolic Heart Failure (RALI-DHF)

July 11, 2012 updated by: Gilead Sciences

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Goettingen, Germany
        • University Medicine Goettingen (UMG)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ranolazine
Drug: Ranolazine
Intravenous treatment followed oral treatment for 13 days.
Other Names:
  • 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 Names:
  • Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to 30 minutes in cardiac catheterization hemodynamic parameters at both resting and paced conditions
Time Frame: Baseline to 30 minutes

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 Outcome Measures

Outcome Measure
Time Frame
Change from baseline to Day 14 in mitral E wave velocity/mitral annular velocity (E/E') ratio
Time Frame: Baseline to Day 14
Baseline to Day 14
Change from baseline to Day 14 in VO2 max
Time Frame: Baseline to Day 14
Baseline to Day 14
Change from baseline to Day 14 in N-terminal pro-brain B-type natriuretic peptide (NT-pro-BNP)
Time Frame: Baseline to Day 14
Baseline to Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Collaborators

University Medicine Göttingen, Cardiac Center

Investigators

  • Principal Investigator: Lars S. Maier, MD, University Medicine Göttingen, Cardiac Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (ACTUAL)

February 1, 2011

Study Completion (ACTUAL)

February 1, 2011

Study Registration Dates

First Submitted

July 12, 2010

First Submitted That Met QC Criteria

July 14, 2010

First Posted (ESTIMATE)

July 16, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

July 12, 2012

Last Update Submitted That Met QC Criteria

July 11, 2012

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-270-0101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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