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

Study Overview
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Brief Summary
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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
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Adverse event data will be covered in Adverse events section.

Official Title
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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)

Conditions
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Hypertension, Pulmonary, Ventricular Dysfunction, Left

Intervention / Treatment
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* Drug: Riociguat (Adempas, BAY63-2521)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riociguat (Adempas, BAY63-2521)<br>Participants received a single oral dose of 1 mg riociguat. | Drug: Riociguat (Adempas, BAY63-2521)<br>* 1 mg single oral dose<br>|
| Placebo Comparator: Placebo<br>Participants received a single oral dose of 1 mg placebo. | Drug: Placebo<br>* Single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak Power Index at Rest | 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 | Before and 1 hour after administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular Stroke Work Index (LVSWI) at Rest | 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 | Before and 1 hour after administration of study drug | 
| Change in Left Ventricular Ejection Fraction (LVEF) at Rest | 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 | Before and 1 hour after administration of study drug | 
| Change in End-systolic Elastance at Rest | 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 | Before and 1 hour after administration of study drug | 
| Change in Peak Power Index During the Cardiopulmonary Exercise Tests | 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 | Before and 1 hour after administration of study drug | 
| Change in Lateral Mitral Annular Peak Systolic Velocity (Sm) During the Cardiopulmonary Exercise Tests | The lateral mitral annular peak systolic velocity (Sm) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. | Before and 1 hour after administration of study drug | 
| Change in Peak Systolic Tricuspid Annular Velocity (RV-Sm) During the Cardiopulmonary Exercise Tests | The peak systolic tricuspid annular velocity (RV-Sm) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. | Before and 1 hour after administration of study drug | 
| Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) During the Cardiopulmonary Exercise Tests | The tricuspid annular plane systolic excursion (TAPSE) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. | Before and 1 hour after administration of study drug | 
| Change in Lateral Mitral Annular Peak Early Diastolic Velocity (E') During the Cardiopulmonary Exercise Tests | The lateral mitral annular peak early diastolic velocity (E') is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. | Before and 1 hour after administration of study drug | 
| Change in the Slope of the Relationship Between Work Rate and Mean Pulmonary Arterial Pressure (PAPmean) During the Cardiopulmonary Exercise Tests | 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. | Before and 1 hour after administration of study drug | 
| Change in the Ventilatory Efficiency (V'E/V'CO2) Measured From Baseline to the Anaerobic Threshold (AT) During the Cardiopulmonary Exercise Tests (CPET) | 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. | Before and 1 hour after administration of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension, Left ventricular dysfunction