Hypertension, Pulmonary, Ventricular Dysfunction, Left
Conditions
Keywords
Pulmonary Hypertension, Left ventricular dysfunction
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.
Interventions
DRUGRiociguat (Adempas, BAY63-2521)
1 mg single oral dose
DRUGPlacebo
Single oral dose
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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. |
| 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 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 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. |
Countries
United States
Participant flow
Recruitment details
Only subjects symptomatic with pulmonary hypertension associated with left ventricular systolic dysfunction (PH-sLVD) could participate in this study.
Pre-assignment details
One subject was screened, randomized and treated during this study. The subject completed the study according to protocol.
Participants by arm
| Arm | Count |
|---|---|
| Riociguat (Adempas, BAY63-2521) Participants received a single oral dose of 1 mg riociguat. | 1 |
| Placebo Participants received a single oral dose of 1 mg placebo. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Riociguat (Adempas, BAY63-2521) | Total |
|---|---|---|
| Age, Customized <65 years | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 1 Participants | 1 Participants |
| Gender Female | 0 Participants | 0 Participants |
| Gender Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
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
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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.
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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.
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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.
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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.
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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.
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.
Secondary
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.
Time frame: Before and 1 hour after administration of study drug
Population: Due to the very low number of patients enrolled in the study, no statistical evaluation was done.