Hypertension, Pulmonary, Ventricular Dysfunction, Left
Conditions
Keywords
Pulmonary Hypertension, Left ventricular dysfunction
Brief summary
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
Detailed description
Pharmacokinetics parameters were regarded as exploratory parameters. Adverse event data will be covered in Adverse events section.
Interventions
DRUGRiociguat (Adempas, BAY63-2521)
up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg)
DRUGPlacebo
Placebo three times a day
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients with symptomatic pulmonary hypertension due to left ventricular systolic dysfunction despite optimized 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 |
|---|---|---|
| Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | The mixed venous oxygen saturation rate (SvO2) is a directly measured hemodynamic parameter. SvO2 is recorded during a right heart catheterization. |
| Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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 |
| Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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 |
| Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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. |
| Osteopontin - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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. |
| Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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 |
| Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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 |
| Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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 |
| Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Pulmonary capillary wedge pressure (PCWP) is a directly measured hemodynamic parameter acquired during a right heart catheterization. |
| Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | The tricuspid annular plane systolic excursion (TAPSE) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. |
| Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Systolic pulmonary arterial pressure (PAPsyst) is a directly measured hemodynamic parameter acquired during a right heart catheterization. |
| Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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 |
| Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Left ventricular end-systolic volume (LVESV) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. |
| Left Ventricular End-diastolic Volume (LVEDV) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Left ventricular end-diastolic volume (LVEDV) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. |
| E-wave Deceleration Time - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | E-wave deceleration time is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination. |
| Ratio of Mitral Peak Velocity of Early Filling to Mitral Peak Velocity of Late Filling (E/A) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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. |
| 6-minute Walking Distance (6MWD) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity. |
| WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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. |
| Percentage of Participants With Clinical Worsening | At visit 6 (16 weeks) | 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. |
| Borg CR 10 Scale - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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"). |
| EQ-5D Utility Score - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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). |
| Minnesota Living With Heart Failure Questionnaire (MLHF) Score - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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). |
| Cystatin C - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Cystatin C is a biomarker for predicting new onset or deteriorating cardiovascular disease. |
| N-terminal Pro-brain Natriuretic Peptide (NT-pro BNP) - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | 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. |
| Troponin T - Change From Baseline to Week 16 | Baseline and visit 6 (16 weeks) | Troponin T is a cardiac-specific protein which is released from damaged or injured heart muscle cells. |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Italy, Japan, Netherlands, Poland, Singapore, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORBayer Study Director
Bayer
Participant flow
Recruitment details
Only subjects with symptomatic pulmonary hypertension associated with left ventricular systolic dysfunction (PH-sLVD) could participate in this study. Subjects must have been pre-treated with optimized CHF therapy.
Pre-assignment details
301 subjects were screened in 84 study centers in 18 countries worldwide. 99 of the 301 screened subjects were not randomized (adverse event \[1\], protocol violation \[1\], screen failure \[87\], withdrawal by subject \[10\]). Of the 202 subjects randomized, one subject did not receive any study medication.
Participants by arm
| Arm | Count |
|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg Participants received riociguat up to 2 mg three times per day (tid) (increasing from 0.5 to 1 to 2 mg). | 67 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg Participants received riociguat up to 1 mg tid (increasing from 0.5 to 1 mg). | 33 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg Participants received riociguat 0.5 mg tid (fixed dose). | 32 |
| Placebo Participants received placebo tid. | 69 |
| Total | 201 |
Baseline characteristics
| Characteristic | Riociguat (Adempas, BAY63-2521) up to 2 mg | Total | Placebo | Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Riociguat (Adempas, BAY63-2521) up to 1 mg |
|---|---|---|---|---|---|
| 6-minute walking distance | 380.9 Meters STANDARD_DEVIATION 125.8 | 390.5 Meters STANDARD_DEVIATION 116.94 | 382.1 Meters STANDARD_DEVIATION 123.51 | 416.6 Meters STANDARD_DEVIATION 95.77 | 401.9 Meters STANDARD_DEVIATION 101.75 |
| Age, Continuous | 59.3 Years STANDARD_DEVIATION 10.8 | 58.1 Years STANDARD_DEVIATION 11.2 | 58.9 Years STANDARD_DEVIATION 11.2 | 57.2 Years STANDARD_DEVIATION 9.9 | 55.1 Years STANDARD_DEVIATION 13.2 |
| Baseline drug and device therapy Aldosterone antagonists | 51 Participants | 153 Participants | 53 Participants | 23 Participants | 26 Participants |
| Baseline drug and device therapy Amiodarone | 9 Participants | 24 Participants | 8 Participants | 4 Participants | 3 Participants |
| Baseline drug and device therapy Angiotensin-converting enzyme inhibitors | 50 Participants | 142 Participants | 46 Participants | 21 Participants | 25 Participants |
| Baseline drug and device therapy Angiotensin II receptor blockers | 20 Participants | 57 Participants | 19 Participants | 10 Participants | 8 Participants |
| Baseline drug and device therapy Beta-blockers | 31 Participants | 100 Participants | 32 Participants | 21 Participants | 16 Participants |
| Baseline drug and device therapy Beta-blockers with alpha-blocking activity | 30 Participants | 86 Participants | 30 Participants | 11 Participants | 15 Participants |
| Baseline drug and device therapy Cardiac devices | 38 Participants | 120 Participants | 44 Participants | 21 Participants | 17 Participants |
| Baseline drug and device therapy Cardiac glycosides | 28 Participants | 74 Participants | 28 Participants | 6 Participants | 12 Participants |
| Baseline drug and device therapy Loop diuretics | 62 Participants | 190 Participants | 68 Participants | 29 Participants | 31 Participants |
| Baseline drug and device therapy Oral anticoagulants | 38 Participants | 102 Participants | 33 Participants | 15 Participants | 16 Participants |
| Baseline drug and device therapy Thiazide diuretics | 12 Participants | 32 Participants | 10 Participants | 7 Participants | 3 Participants |
| Body mass index | 28.87 kg/m^2 STANDARD_DEVIATION 5.27 | 28.73 kg/m^2 STANDARD_DEVIATION 5.44 | 28.65 kg/m^2 STANDARD_DEVIATION 5.89 | 29.20 kg/m^2 STANDARD_DEVIATION 5.64 | 28.16 kg/m^2 STANDARD_DEVIATION 4.72 |
| Etiology Data missing | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Etiology Ischemic cardiomyopathy | 30 Participants | 90 Participants | 34 Participants | 14 Participants | 12 Participants |
| Etiology Non-ischemic cardiomyopathy | 37 Participants | 108 Participants | 34 Participants | 17 Participants | 20 Participants |
| Glomerular filtration rate (GFR) | 65.1 mL/min/1.73m^2 STANDARD_DEVIATION 19.1 | 68.7 mL/min/1.73m^2 STANDARD_DEVIATION 19.91 | 68.7 mL/min/1.73m^2 STANDARD_DEVIATION 19.9 | 72.0 mL/min/1.73m^2 STANDARD_DEVIATION 17.9 | 72.6 mL/min/1.73m^2 STANDARD_DEVIATION 22.7 |
| Left ventricular ejection fraction (LVEF) | 28.4 Percentage STANDARD_DEVIATION 5.72 | 27.8 Percentage STANDARD_DEVIATION 5.24 | 27.1 Percentage STANDARD_DEVIATION 5.02 | 27.0 Percentage STANDARD_DEVIATION 5.21 | 28.8 Percentage STANDARD_DEVIATION 4.54 |
| Number of participants with atrial fibrillation | 9 Participants | 24 Participants | 9 Participants | 3 Participants | 3 Participants |
| Number of participants with atrial flutter | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Number of participants with diabetes mellitus (including subtypes) | 30 Participants | 87 Participants | 34 Participants | 13 Participants | 10 Participants |
| Number of participants with pacemaker rhythm | 17 Participants | 50 Participants | 17 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Female | 12 Participants | 29 Participants | 8 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 55 Participants | 172 Participants | 61 Participants | 26 Participants | 30 Participants |
| WHO (World Health Organization) functional class II | 35 Participants | 120 Participants | 42 Participants | 23 Participants | 20 Participants |
| WHO (World Health Organization) functional class III | 31 Participants | 76 Participants | 23 Participants | 9 Participants | 13 Participants |
| WHO (World Health Organization) functional class IV | 1 Participants | 5 Participants | 4 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 67 | 1 / 33 | 1 / 32 | 0 / 69 | 29 / 142 |
| other Total, other adverse events | 61 / 67 | 29 / 33 | 24 / 32 | 52 / 69 | 136 / 142 |
| serious Total, serious adverse events | 23 / 67 | 7 / 33 | 7 / 32 | 18 / 69 | 116 / 142 |
Outcome results
Primary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF \[safety analysis set\]/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 | -6.1 mmHg | Standard Deviation 9.68 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 | -0.8 mmHg | Standard Deviation 8.41 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 | -4.5 mmHg | Standard Deviation 7.35 |
| Placebo | Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 | -4.0 mmHg | Standard Deviation 9 |
p-value: 0.104495% CI: [-5.99, 0.057]ANCOVA
p-value: 0.529295% CI: [-5.71, 2.94]ANCOVA
p-value: 0.027895% CI: [-8.52, -0.5]ANCOVA
p-value: 0.382195% CI: [-2.25, 5.84]ANCOVA
p-value: 0.208495% CI: [-1.76, 8.02]ANCOVA
p-value: 0.544295% CI: [-5.66, 3]ANCOVA
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | 6-minute Walking Distance (6MWD) - Change From Baseline to Week 16 | 31.425 m | Standard Deviation 83.386 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | 6-minute Walking Distance (6MWD) - Change From Baseline to Week 16 | 25.379 m | Standard Deviation 84.244 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | 6-minute Walking Distance (6MWD) - Change From Baseline to Week 16 | -2.784 m | Standard Deviation 90.324 |
| Placebo | 6-minute Walking Distance (6MWD) - Change From Baseline to Week 16 | 17.857 m | Standard Deviation 80.851 |
95% CI: [-18.48, 38.81]
95% CI: [-26.76, 42.59]
95% CI: [-44.08, 31.78]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16 | 0.020 µmol/L | Standard Deviation 0.115 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16 | 0.026 µmol/L | Standard Deviation 0.118 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16 | 0.006 µmol/L | Standard Deviation 0.098 |
| Placebo | Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16 | 0.020 µmol/L | Standard Deviation 0.09 |
95% CI: [-0.04, 0.03]
95% CI: [-0.04, 0.05]
95% CI: [-0.07, 0.03]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Borg CR 10 Scale - Change From Baseline to Week 16 | 0.269 Scores on a scale | Standard Deviation 1.9 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Borg CR 10 Scale - Change From Baseline to Week 16 | -0.804 Scores on a scale | Standard Deviation 2.319 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Borg CR 10 Scale - Change From Baseline to Week 16 | -0.682 Scores on a scale | Standard Deviation 1.516 |
| Placebo | Borg CR 10 Scale - Change From Baseline to Week 16 | 0.187 Scores on a scale | Standard Deviation 2.64 |
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Cystatin C - Change From Baseline to Week 16 | 39.3 ng/mL | Standard Deviation 232.7 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Cystatin C - Change From Baseline to Week 16 | 11.2 ng/mL | Standard Deviation 218.5 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Cystatin C - Change From Baseline to Week 16 | 71.2 ng/mL | Standard Deviation 140.8 |
| Placebo | Cystatin C - Change From Baseline to Week 16 | 58.6 ng/mL | Standard Deviation 242.9 |
95% CI: [-117.58, 68.33]
95% CI: [-162.46, 55.88]
95% CI: [-135.78, 119.06]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | EQ-5D Utility Score - Change From Baseline to Week 16 | 0.073 Scores on a scale | Standard Deviation 0.211 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | EQ-5D Utility Score - Change From Baseline to Week 16 | 0.016 Scores on a scale | Standard Deviation 0.242 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | EQ-5D Utility Score - Change From Baseline to Week 16 | 0.004 Scores on a scale | Standard Deviation 0.166 |
| Placebo | EQ-5D Utility Score - Change From Baseline to Week 16 | 0.018 Scores on a scale | Standard Deviation 0.201 |
95% CI: [-0.04, 0.1]
95% CI: [-0.07, 0.09]
95% CI: [-0.07, 0.11]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | E-wave Deceleration Time - Change From Baseline to Week 16 | 2.857 msec | Standard Deviation 31.47 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | E-wave Deceleration Time - Change From Baseline to Week 16 | -0.636 msec | Standard Deviation 38.138 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | E-wave Deceleration Time - Change From Baseline to Week 16 | 8.000 msec | Standard Deviation 39.542 |
| Placebo | E-wave Deceleration Time - Change From Baseline to Week 16 | -1.208 msec | Standard Deviation 43.937 |
95% CI: [-7.38, 17.95]
95% CI: [-9.79, 22.73]
95% CI: [-6.14, 26.84]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16 | 6.599 Percentage | Standard Deviation 43.187 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16 | 12.659 Percentage | Standard Deviation 41.769 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16 | 5.529 Percentage | Standard Deviation 48.322 |
| Placebo | Left Ventricular Ejection Fraction (LVEF) - Change From Baseline to Week 16 | 11.121 Percentage | Standard Deviation 42.989 |
95% CI: [-0.21, 1.24]
95% CI: [-0.07, 1.69]
95% CI: [-0.74, 1.15]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Left Ventricular End-diastolic Volume (LVEDV) - Change From Baseline to Week 16 | 6.599 mL | Standard Deviation 43.187 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Left Ventricular End-diastolic Volume (LVEDV) - Change From Baseline to Week 16 | 12.659 mL | Standard Deviation 41.769 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Left Ventricular End-diastolic Volume (LVEDV) - Change From Baseline to Week 16 | 5.529 mL | Standard Deviation 48.322 |
| Placebo | Left Ventricular End-diastolic Volume (LVEDV) - Change From Baseline to Week 16 | 11.121 mL | Standard Deviation 42.989 |
95% CI: [-21.13, 12.6]
95% CI: [-17.59, 23.16]
95% CI: [-26.43, 17.2]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16 | 1.805 mL | Standard Deviation 31.735 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16 | 6.415 mL | Standard Deviation 28.832 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16 | 1.507 mL | Standard Deviation 34.033 |
| Placebo | Left Ventricular End-systolic Volume (LVESV) - Change From Baseline to Week 16 | 7.295 mL | Standard Deviation 32.311 |
95% CI: [-17.33, 7.22]
95% CI: [-14.55, 15.11]
95% CI: [-21.05, 10.69]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Minnesota Living With Heart Failure Questionnaire (MLHF) Score - Change From Baseline to Week 16 | -10.789 Scores on a scale | Standard Deviation 22.232 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Minnesota Living With Heart Failure Questionnaire (MLHF) Score - Change From Baseline to Week 16 | -5.132 Scores on a scale | Standard Deviation 14.111 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Minnesota Living With Heart Failure Questionnaire (MLHF) Score - Change From Baseline to Week 16 | -7.595 Scores on a scale | Standard Deviation 18.651 |
| Placebo | Minnesota Living With Heart Failure Questionnaire (MLHF) Score - Change From Baseline to Week 16 | 0.211 Scores on a scale | Standard Deviation 15.964 |
95% CI: [-12.81, -0.78]
95% CI: [-13.96, 0.35]
95% CI: [-15.29, 0.28]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | N-terminal Pro-brain Natriuretic Peptide (NT-pro BNP) - Change From Baseline to Week 16 | -168.42 pg/mL | Standard Deviation 1585.28 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | N-terminal Pro-brain Natriuretic Peptide (NT-pro BNP) - Change From Baseline to Week 16 | -213.48 pg/mL | Standard Deviation 1204.24 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | N-terminal Pro-brain Natriuretic Peptide (NT-pro BNP) - Change From Baseline to Week 16 | -215.71 pg/mL | Standard Deviation 769.16 |
| Placebo | N-terminal Pro-brain Natriuretic Peptide (NT-pro BNP) - Change From Baseline to Week 16 | 171.51 pg/mL | Standard Deviation 2123.55 |
95% CI: [-1055.23, 240.54]
95% CI: [-1212.74, 318.22]
95% CI: [-1369.48, 334.53]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Osteopontin - Change From Baseline to Week 16 | -13.400 µg/mL | Standard Deviation 44.931 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Osteopontin - Change From Baseline to Week 16 | -0.852 µg/mL | Standard Deviation 22.396 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Osteopontin - Change From Baseline to Week 16 | -2.722 µg/mL | Standard Deviation 29.379 |
| Placebo | Osteopontin - Change From Baseline to Week 16 | -4.588 µg/mL | Standard Deviation 77.576 |
95% CI: [-30.79, 2.53]
95% CI: [-32.89, 7.43]
95% CI: [-41.53, 5]
Secondary
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)
Population: Intent to Treat (ITT) - a randomized participant was valid for ITT analyses if at least one dose of study medication was administered. Only participants with a baseline and at least one post-baseline measurement were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Percentage of Participants With Clinical Worsening | 23.9 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Percentage of Participants With Clinical Worsening | 15.1 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Percentage of Participants With Clinical Worsening | 15.6 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Worsening | 21.7 Percentage of participants |
95% CI: [-13.36, 14.61]
95% CI: [-24.32, 5.39]
95% CI: [-22.26, 10.13]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16 | -3.93 mmHg | Standard Deviation 9.381 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16 | 0.25 mmHg | Standard Deviation 9.001 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16 | -2.818 mmHg | Standard Deviation 7.842 |
| Placebo | Pulmonary Capillary Wedge Pressure (PCWP) - Change From Baseline to Week 16 | -2.68 mmHg | Standard Deviation 7.791 |
95% CI: [-5, 0.8]
95% CI: [-2.1, 4.9]
95% CI: [-4.9, 2.7]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16 | -152.60 dyn*s*cm^-5*m^2 | Standard Deviation 250.366 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16 | -61.763 dyn*s*cm^-5*m^2 | Standard Deviation 202.138 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16 | -91.65 dyn*s*cm^-5*m^2 | Standard Deviation 237.256 |
| Placebo | Pulmonary Vascular Resistance Index (PVRi) - Change From Baseline to Week 16 | -76.47 dyn*s*cm^-5*m^2 | Standard Deviation 311.693 |
95% CI: [-172.9, 5.5]
95% CI: [-162.1, 45.6]
95% CI: [-153.7, 67.1]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 | -78.15 dyn*s*cm^-5 | Standard Deviation 125.261 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 | -33.05 dyn*s*cm^-5 | Standard Deviation 99.322 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 | -51.44 dyn*s*cm^-5 | Standard Deviation 124.107 |
| Placebo | Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 | -36.97 dyn*s*cm^-5 | Standard Deviation 157.523 |
95% CI: [-89.4, -3.8]
95% CI: [-84.9, 20.4]
95% CI: [-83, 30]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Ratio of Mitral Peak Velocity of Early Filling to Mitral Peak Velocity of Late Filling (E/A) - Change From Baseline to Week 16 | -0.247 E/A ratio | Standard Deviation 0.957 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Ratio of Mitral Peak Velocity of Early Filling to Mitral Peak Velocity of Late Filling (E/A) - Change From Baseline to Week 16 | 0.141 E/A ratio | Standard Deviation 1.261 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Ratio of Mitral Peak Velocity of Early Filling to Mitral Peak Velocity of Late Filling (E/A) - Change From Baseline to Week 16 | -0.063 E/A ratio | Standard Deviation 0.884 |
| Placebo | Ratio of Mitral Peak Velocity of Early Filling to Mitral Peak Velocity of Late Filling (E/A) - Change From Baseline to Week 16 | -0.175 E/A ratio | Standard Deviation 1.079 |
95% CI: [-0.55, 0.24]
95% CI: [-0.34, 0.67]
95% CI: [-0.45, 0.56]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16 | -651.98 dyn*s*cm^-5*m^2 | Standard Deviation 757.617 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16 | -217.14 dyn*s*cm^-5*m^2 | Standard Deviation 742.465 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16 | -100.31 dyn*s*cm^-5*m^2 | Standard Deviation 612.46 |
| Placebo | Systemic Vascular Resistance Index (SVRi) - Change From Baseline to Week 16 | -195.11 dyn*s*cm^-5*m^2 | Standard Deviation 853.927 |
95% CI: [-687.4, -205.6]
95% CI: [-530.4, 67.2]
95% CI: [-353.7, 283.7]
Secondary
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
Time frame: Baseline and visit 6 (16 weeks)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 | -340.44 dyn*s*cm^-5 | Standard Deviation 394.87 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 | -118.72 dyn*s*cm^-5 | Standard Deviation 369.865 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 | -67.46 dyn*s*cm^-5 | Standard Deviation 315.097 |
| Placebo | Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 | -94.37 dyn*s*cm^-5 | Standard Deviation 431.049 |
95% CI: [-363.4, -115.3]
95% CI: [-274.4, 32.6]
95% CI: [-189.3, 138.2]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16 | -7.69 mmHg | Standard Deviation 14.251 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16 | -2.89 mmHg | Standard Deviation 12.333 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16 | -5.86 mmHg | Standard Deviation 11.589 |
| Placebo | Systolic Pulmonary Arterial Pressure (PAPsyst) - Change From Baseline to Week 16 | -4.49 mmHg | Standard Deviation 13.717 |
95% CI: [-8.76, 1.09]
95% CI: [-6.05, 6.01]
95% CI: [-8.93, 4.06]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16 | -2.16 mmHg | Standard Deviation 4.795 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16 | -1.01 mmHg | Standard Deviation 5.224 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16 | -1.65 mmHg | Standard Deviation 4.652 |
| Placebo | Transpulmonary Pressure Gradient (TPG) - Change From Baseline to Week 16 | -1.37 mmHg | Standard Deviation 7.001 |
95% CI: [-3.1, 0.5]
95% CI: [-3.1, 1.3]
95% CI: [-3.2, 1.5]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16 | 0.584 mm | Standard Deviation 2.344 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16 | 1.140 mm | Standard Deviation 2.986 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16 | 0.304 mm | Standard Deviation 2.109 |
| Placebo | Tricuspid Annular Plane Systolic Excursion (TAPSE) - Change From Baseline to Week 16 | 0.393 mm | Standard Deviation 1.586 |
95% CI: [-0.58, 1.14]
95% CI: [-0.23, 1.87]
95% CI: [-1.11, 1.06]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Troponin T - Change From Baseline to Week 16 | 0.005 µg/L | Standard Deviation 0.027 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Troponin T - Change From Baseline to Week 16 | -0.008 µg/L | Standard Deviation 0.042 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Troponin T - Change From Baseline to Week 16 | -0.001 µg/L | Standard Deviation 0.006 |
| Placebo | Troponin T - Change From Baseline to Week 16 | 0.003 µg/L | Standard Deviation 0.015 |
95% CI: [-0.01, 0.01]
95% CI: [-0.02, 0]
95% CI: [-0.02, 0.01]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 | 1.98 Percentage | Standard Deviation 7.084 |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 | 0.46 Percentage | Standard Deviation 7.866 |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 | -0.21 Percentage | Standard Deviation 5.969 |
| Placebo | Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 | 1.28 Percentage | Standard Deviation 9.259 |
95% CI: [-0.83, 4.56]
95% CI: [-3.12, 3.51]
95% CI: [-3.31, 3.77]
Secondary
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)
Population: Per-protocol set (PPS) - A subject was included in the PPS if he/she was valid for SAF/ITT and showed no major protocol deviations affecting efficacy. Only participants with a baseline and at least one post-baseline measurement were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) up to 2 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | -1 | 20.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 1 | 5.6 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 2 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 0 | 74.1 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | -1 | 21.4 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 1 | 3.6 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) up to 1 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 0 | 75 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 0 | 68.2 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | -1 | 22.7 Percentage of participants |
| Riociguat (Adempas, BAY63-2521) Fixed 0.5 mg | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 1 | 9.1 Percentage of participants |
| Placebo | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | -1 | 19.6 Percentage of participants |
| Placebo | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 1 | 8.9 Percentage of participants |
| Placebo | WHO (World Health Organization) Functional Class - Change From Baseline to Week 16 | 0 | 71.4 Percentage of participants |