A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction (LEPHT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01065454
First received: February 8, 2010
Last updated: January 25, 2014
Last verified: January 2014

February 8, 2010
January 25, 2014
April 2010
June 2012   (final data collection date for primary outcome measure)
Pulmonary Artery Mean Pressure (PAPmean) at Rest - Change From Baseline to Week 16 [ Time Frame: Baseline and visit 6 (16 weeks) ] [ Designated as safety issue: No ]
Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.
Pulmonary artery mean pressure at rest [ Time Frame: Change from baseline after 16 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01065454 on ClinicalTrials.gov Archive Site
  • Venous Oxygen Saturation (SvO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and visit 6 (16 weeks) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.
  • Adverse event collection [ Time Frame: Until week 16 + 4 weeks Follow-up ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profile of Riociguat [ Time Frame: Until week 16 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction
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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Hypertension, Pulmonary
  • Ventricular Dysfunction, Left
  • Drug: Riociguat (Adempas, BAY63-2521)
    up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg)
  • Drug: Riociguat (Adempas, BAY63-2521)
    up to 1 mg three times a day (increasing from 0.5 to 1 mg)
  • Drug: Riociguat (Adempas, BAY63-2521)
    fixed 0.5 mg three times a day
  • Drug: Placebo
    Placebo three times a day
  • 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).
    Intervention: Drug: Riociguat (Adempas, BAY63-2521)
  • Experimental: Riociguat (Adempas, BAY63-2521) up to 1 mg
    Participants received riociguat up to 1 mg tid (increasing from 0.5 to 1 mg).
    Intervention: Drug: Riociguat (Adempas, BAY63-2521)
  • Experimental: Riociguat (Adempas, BAY63-2521) fixed 0.5 mg
    Participants received riociguat 0.5 mg tid (fixed dose).
    Intervention: Drug: Riociguat (Adempas, BAY63-2521)
  • Placebo Comparator: Placebo
    Participants received placebo tid.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
201
May 2017
June 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Belgium,   Canada,   China,   Czech Republic,   Denmark,   France,   Germany,   Italy,   Japan,   Netherlands,   Poland,   Singapore,   Spain,   Sweden,   Switzerland,   United Kingdom
 
NCT01065454
14308, 2009-015878-35
Yes
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP