Hemodynamic and Echocardiographic Assessment of Riociguat Effects on Myocardial Wall Contractility and Relaxation Kinetics (HEARTWORK)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01065051
First received: February 8, 2010
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

The aim of this study is to assess whether oral Riociguat affects the left ventricular contractility and relaxation in patients with pulmonary hypertension associated with left ventricular systolic dysfunction


Condition Intervention Phase
Hypertension, Pulmonary
Ventricular Dysfunction, Left
Drug: Riociguat (Adempas, BAY63-2521)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Effects of a Single Dose of 1 mg Riociguat (BAY63-2521) on Myocardial Contractility and Relaxation in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction (PH-sLVD)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Change in Peak Power Index at Rest [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The peak power index is a calculated hemodynamic parameter. It is derived from the directly measured parameters mean systolic arterial pressure (SAPmean) and mean pulmonary capillary wedge pressure (PCWPmean). These 2 parameters are acquired during a right heart catheterization. The peak power index is calculated from the maximal power (which also takes the calculated parameter cardiac output into account) divided by the left ventricular end-diastolic volume (LVEDV). Formula: Peak Power Index = (SAPmean - PCWPmean)*CO [cardiac output]*16.667/LVEDV


Secondary Outcome Measures:
  • Change in Left Ventricular Stroke Work Index (LVSWI) at Rest [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The left ventricular stroke work index (LVSWI) is a calculated hemodynamic parameter. It is derived from the directly measured parameters mean systolic arterial pressure (SAPmean) and mean pulmonary capillary wedge pressure (PCWPmean). These 2 parameters are acquired during a right heart catheterization. The LVSWI is also dependent of the calculated hemodynamic parameter stroke volume index (SVI). Formula: LVSWI = (SAPmean - PCWPmean)*SVI*0.0136

  • Change in Left Ventricular Ejection Fraction (LVEF) at Rest [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a non-invasive echocardiography examination. Formula: LEVF = 100*(LVEDV - LVESV)/LVEDV

  • Change in End-systolic Elastance at Rest [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The end-systolic elastance is a calculated hemodynamic parameter. It is approximated by the directly measured hemodynamic parameter end-systolic pressure divided by the directly measured echocardiography parameter left ventricular end-systolic volume (LVESV). The end-systolic pressure is acquired during a right heart catheterization. The LVESV is acquired during a non-invasive echocardiography examination. Approximated by end-systolic pressure/LVESV

  • Change in Peak Power Index During the Cardiopulmonary Exercise Tests [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The peak power index is a calculated hemodynamic parameter. It is derived from the directly measured parameters mean systolic arterial pressure (SAPmean) and mean pulmonary capillary wedge pressure (PCWPmean). These 2 parameters are acquired during a right heart catheterization. Formula: Peak Power Index = (SAPmean - PCWPmean)*CO*16.667/LVEDV

  • Change in Lateral Mitral Annular Peak Systolic Velocity (Sm) During the Cardiopulmonary Exercise Tests [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The lateral mitral annular peak systolic velocity (Sm) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.

  • Change in Peak Systolic Tricuspid Annular Velocity (RV-Sm) During the Cardiopulmonary Exercise Tests [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The peak systolic tricuspid annular velocity (RV-Sm) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.

  • Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) During the Cardiopulmonary Exercise Tests [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The tricuspid annular plane systolic excursion (TAPSE) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.

  • Change in Lateral Mitral Annular Peak Early Diastolic Velocity (E') During the Cardiopulmonary Exercise Tests [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The lateral mitral annular peak early diastolic velocity (E') is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.

  • Change in the Slope of the Relationship Between Work Rate and Mean Pulmonary Arterial Pressure (PAPmean) During the Cardiopulmonary Exercise Tests [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    The slope of the relationship between work rate during cardiopulmonary exercise tests and PAPmean is derived from the directly measured hemodynamic parameter mean pulmonary arterial pressure (PAPmean). PAPmean is acquired during a right heart catheterization.

  • Change in the Ventilatory Efficiency (V'E/V'CO2) Measured From Baseline to the Anaerobic Threshold (AT) During the Cardiopulmonary Exercise Tests (CPET) [ Time Frame: Before and 1 hour after administration of study drug ] [ Designated as safety issue: No ]
    Ventilatory efficiency (V'E/V'CO2) and anaerobic threshold (AT) were parameters directly measured or derived by computed analysis from the spiroergometry system during the cardiopulmonary exercise test.


Enrollment: 1
Study Start Date: November 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Riociguat (Adempas, BAY63-2521)
Participants received a single oral dose of 1 mg riociguat.
Drug: Riociguat (Adempas, BAY63-2521)
1 mg single oral dose
Placebo Comparator: Placebo
Participants received a single oral dose of 1 mg placebo.
Drug: Placebo
Single oral dose

Detailed Description:

Adverse event data will be covered in Adverse events section.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients with symptomatic pulmonary hypertension due to left ventricular systolic dysfunction despite standard heart failure therapy

Exclusion Criteria:

  • Types of pulmonary hypertension other than group 2.1 of Dana Point Classification
  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: NCT01065051

Locations
United States, Massachusetts
Boston, Massachusetts, United States, 02114-2696
United States, Minnesota
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01065051     History of Changes
Other Study ID Numbers: 14549
Study First Received: February 8, 2010
Results First Received: November 4, 2013
Last Updated: December 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Pulmonary Hypertension
Left ventricular dysfunction

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Ventricular Dysfunction
Ventricular Dysfunction, Left
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Heart Diseases

ClinicalTrials.gov processed this record on September 16, 2014