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

Phase 2

Terminated

• Conditions: Hypertension, Pulmonary; Ventricular Dysfunction, Left
• Interventions: Drug: Riociguat (Adempas, BAY63-2521); Drug: Placebo

• Registration Number: NCT01065051
• Lead Sponsor: Bayer

Brief Summary

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

Detailed Description

Adverse event data will be covered in Adverse events section.

Study Timeline

• Study First Submitted: 2010-02-08
• Study First Submitted QC: 2010-02-08
• Study First Posted: 2010-02-09
• Study Start: 2010-11
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Results First Submitted: 2013-11-04
• Status Verified: 2013-12
• Results First Submitted QC: 2013-12-31
• Last Update Submitted: 2013-12-31
• Results First Posted: 2014-01-06
• Last Update Posted: 2014-01-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Riociguat (Adempas, BAY63-2521)	Riociguat (Adempas, BAY63-2521)	Participants received a single oral dose of 1 mg riociguat.
Placebo	Placebo	Participants received a single oral dose of 1 mg placebo.

Primary Outcome Measures

Name	Time	Method
Change in Peak Power Index at Rest	Before and 1 hour after administration of study drug	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

Name	Time	Method
Change in the Ventilatory Efficiency (V'E/V'CO2) Measured From Baseline to the Anaerobic Threshold (AT) During the Cardiopulmonary Exercise Tests (CPET)	Before and 1 hour after administration of study drug	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.
Change in Peak Power Index During the Cardiopulmonary Exercise Tests	Before and 1 hour after administration of study drug	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 Peak Systolic Tricuspid Annular Velocity (RV-Sm) During the Cardiopulmonary Exercise Tests	Before and 1 hour after administration of study drug	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	Before and 1 hour after administration of study drug	The tricuspid annular plane systolic excursion (TAPSE) 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	Before and 1 hour after administration of study drug	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 Left Ventricular Stroke Work Index (LVSWI) at Rest	Before and 1 hour after administration of study drug	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	Before and 1 hour after administration of study drug	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	Before and 1 hour after administration of study drug	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 Lateral Mitral Annular Peak Systolic Velocity (Sm) During the Cardiopulmonary Exercise Tests	Before and 1 hour after administration of study drug	The lateral mitral annular peak systolic velocity (Sm) 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	Before and 1 hour after administration of study drug	The lateral mitral annular peak early diastolic velocity (E') is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.