The aim of this study is to assess whether increasing oral doses of Riociguat are safe and improve the well-being, symptoms and outcome in patients with pulmonary hypertension associated with left ventricular systolic dysfunction
Pharmacokinetics parameters were regarded as exploratory parameters. Adverse event data will be covered in Adverse events section.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
202
up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg)
up to 1 mg three times a day (increasing from 0.5 to 1 mg)
fixed 0.5 mg three times a day
Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16
Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.
Time frame: Baseline and visit 6 (16 weeks)
Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16
The mixed venous oxygen saturation rate (SvO2) is a directly measured hemodynamic parameter. SvO2 is recorded during a right heart catheterization.
Time frame: Baseline and visit 6 (16 weeks)
Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16
The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80\*(PAPmean - PCWP)/CO
Time frame: Baseline and visit 6 (16 weeks)
Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16
The pulmonary vascular resistance index (PVRi) is a calculated hemodynamic parameter. PVRi is derived from the pulmonary vascular resistance (PVR) normalized by the body surface area (BSA). Formula: PVRi = 80\*(PAPmean - PCWP)\*BSA/CO
Time frame: Baseline and visit 6 (16 weeks)
Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16
The systemic vascular resistance (SVR) is a calculated hemodynamic parameter. SVR is derived from the directly measured parameter mean right atrial pressure (RAPmean) and the calculated parameter mean systemic arterial pressure (SAPmean) divided by the cardiac output (CO). RAPmean is acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: SVR = 80\*(SAPmean - RAPmean)/CO
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Placebo three times a day
Unnamed facility
Los Angeles, California, United States
Unnamed facility
San Diego, California, United States
Unnamed facility
Torrance, California, United States
Unnamed facility
Westminster, California, United States
Unnamed facility
Miami, Florida, United States
Unnamed facility
Iowa City, Iowa, United States
Unnamed facility
Baltimore, Maryland, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Rochester, Minnesota, United States
Unnamed facility
St Louis, Missouri, United States
...and 73 more locations
Time frame: Baseline and visit 6 (16 weeks)
Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16
The systemic vascular resistance index (SVRi) is a calculated hemodynamic parameter. SVRi is derived from the systemic vascular resistance (SVR) normalized by the body surface area (BSA). Formula: SVRi = 80\*(SAPmean - RAPmean)\*BSA/CO
Time frame: Baseline and visit 6 (16 weeks)
Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16
The transpulmonary pressure gradient (TPG) is a calculated hemodynamic parameter. TPG is calculated from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP). These 2 parameters are acquired during a right heart catheterization. Formula: TPG = PAPmean - PCWP
Time frame: Baseline and visit 6 (16 weeks)
Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16
Pulmonary capillary wedge pressure (PCWP) is a directly measured hemodynamic parameter acquired during a right heart catheterization.
Time frame: Baseline and visit 6 (16 weeks)
Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16
The tricuspid annular plane systolic excursion (TAPSE) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.
Time frame: Baseline and visit 6 (16 weeks)
Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16
Systolic pulmonary arterial pressure (PAPsyst) is a directly measured hemodynamic parameter acquired during a right heart catheterization.
Time frame: Baseline and visit 6 (16 weeks)
Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16
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: Baseline and visit 6 (16 weeks)
Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16
Left ventricular end-systolic volume (LVESV) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.
Time frame: Baseline and visit 6 (16 weeks)
Left Ventricular End-diastolic Volume (LVEDV) - Change From Baseline to Week 16
Left ventricular end-diastolic volume (LVEDV) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.
Time frame: Baseline and visit 6 (16 weeks)
E-wave Deceleration Time - Change From Baseline to Week 16
E-wave deceleration time is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.
Time frame: Baseline and visit 6 (16 weeks)
Ratio of Mitral Peak Velocity of Early Filling to Mitral Peak Velocity of Late Filling (E/A) - Change From Baseline to Week 16
E/A ratio is a measured echocardiography parameter and describes the ratio of mitral peak velocity of early filling to mitral peak velocity of late filling. It is acquired during a non-invasive echocardiography examination.
Time frame: Baseline and visit 6 (16 weeks)
6-minute Walking Distance (6MWD) - Change From Baseline to Week 16
6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
Time frame: Baseline and visit 6 (16 weeks)
WHO (World Health Organization) Functional Class - Change From Baseline to Week 16
The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement, changes to a higher functional class resemble deterioration of PAH.
Time frame: Baseline and visit 6 (16 weeks)
Percentage of Participants With Clinical Worsening
The combined endpoint "time to clinical worsening", made up of the following components, defined by the first occurrence: all cause mortality, including cardiovascular mortality; first hospitalization for a cardiovascular event, including heart failure, acute myocardial infarction, stroke or ventricular arrhythmia; upgrade of the HTx (heart transplantation) status to next higher level; need for IV diuretics; persistent worsening of WHO functional class due to deterioration of PH or cardiac function.
Time frame: At visit 6 (16 weeks)
Borg CR 10 Scale - Change From Baseline to Week 16
The Borg CR10 Scale is a patient reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the patient's exertion during a physical test. Low values indicate low levels of exertion, high values indicate more intense exertion reported by the patient. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal").
Time frame: Baseline and visit 6 (16 weeks)
EQ-5D Utility Score - Change From Baseline to Week 16
EQ-5D utility score is a Quality-of-Life patient reported outcome measure. An increase in the utility score represents an improvement in quality of life. The score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Baseline and visit 6 (16 weeks)
Minnesota Living With Heart Failure Questionnaire (MLHF) Score - Change From Baseline to Week 16
The self-reported Minnesota Living with Heart Failure questionnaire (MLHF) is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The MLHF total score can range from 0 (best) to 105 (worst).
Time frame: Baseline and visit 6 (16 weeks)
Cystatin C - Change From Baseline to Week 16
Cystatin C is a biomarker for predicting new onset or deteriorating cardiovascular disease.
Time frame: Baseline and visit 6 (16 weeks)
N-terminal Pro-brain Natriuretic Peptide (NT-pro BNP) - Change From Baseline to Week 16
N-terminal pro-brain natriuretic peptide (NT-pro BNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.
Time frame: Baseline and visit 6 (16 weeks)
Troponin T - Change From Baseline to Week 16
Troponin T is a cardiac-specific protein which is released from damaged or injured heart muscle cells.
Time frame: Baseline and visit 6 (16 weeks)
Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxides. Recent clinical studies have indicated that ADMA may have diagnostic relevance as a novel cardiovascular risk marker.
Time frame: Baseline and visit 6 (16 weeks)
Osteopontin - Change From Baseline to Week 16
Osteopontin is a cytokine-like pro-fibrotic mediator, which is expressed in cardiovascular tissues. Its expression is induced by increased pressure and volume load in the myocardium, kidney and lung. Therefore, osteopontin may be used as a prognostic marker in patients with cardiovascular diseases.
Time frame: Baseline and visit 6 (16 weeks)