A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction (LEPHT)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01065454 |
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Recruitment Status :
Active, not recruiting
First Posted : February 9, 2010
Results First Posted : December 25, 2013
Last Update Posted : March 27, 2023
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Sponsor:
Bayer
Information provided by (Responsible Party):
Bayer
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypertension, Pulmonary Ventricular Dysfunction, Left | Drug: Riociguat (Adempas, BAY63-2521) Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 202 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Randomized, Double Blind, Placebo Controlled, Parallel Group, Multi-center Study to Evaluate the Hemodynamic Effects of Riociguat (BAY 63-2521) as Well as Safety and Kinetics in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction |
| Actual Study Start Date : | April 14, 2010 |
| Actual Primary Completion Date : | June 6, 2012 |
| Estimated Study Completion Date : | December 31, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hypertension
MedlinePlus related topics:
Pulmonary Hypertension
Drug Information available for:
Riociguat
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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).
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Drug: Riociguat (Adempas, BAY63-2521)
up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg) |
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Experimental: Riociguat (Adempas, BAY63-2521) up to 1 mg
Participants received riociguat up to 1 mg tid (increasing from 0.5 to 1 mg).
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Drug: Riociguat (Adempas, BAY63-2521)
up to 1 mg three times a day (increasing from 0.5 to 1 mg) |
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Experimental: Riociguat (Adempas, BAY63-2521) fixed 0.5 mg
Participants received riociguat 0.5 mg tid (fixed dose).
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Drug: Riociguat (Adempas, BAY63-2521)
fixed 0.5 mg three times a day |
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Placebo Comparator: Placebo
Participants received placebo tid.
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Drug: Placebo
Placebo three times a day |
Primary Outcome Measures :
- Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 [ Time Frame: 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 Outcome Measures :
- Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
- Systemic Vascular Resistance (SVR) - Change From Baseline to Week 16 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline and visit 6 (16 weeks) ]Troponin T is a cardiac-specific protein which is released from damaged or injured heart muscle cells.
- Asymmetric Dimethylarginine (ADMA) - Change From Baseline to Week 16 [ Time Frame: 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 [ Time Frame: 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.
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| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01065454
Locations
Show 83 study locations
Sponsors and Collaborators
Bayer
Investigators
| Study Director: | Bayer Study Director | Bayer |
Publications of Results:
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT01065454 |
| Other Study ID Numbers: |
14308 2009-015878-35 ( EudraCT Number ) |
| First Posted: | February 9, 2010 Key Record Dates |
| Results First Posted: | December 25, 2013 |
| Last Update Posted: | March 27, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Bayer:
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Pulmonary Hypertension Left ventricular dysfunction |
Additional relevant MeSH terms:
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Hypertension, Pulmonary Hypertension Ventricular Dysfunction Ventricular Dysfunction, Left Vascular Diseases Cardiovascular Diseases |
Lung Diseases Respiratory Tract Diseases Heart Diseases Riociguat Enzyme Activators Molecular Mechanisms of Pharmacological Action |