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: September 23, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Hypertension, Pulmonary
Ventricular Dysfunction, Left
Drug: Riociguat (Adempas, BAY63-2521)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 201
Study Start Date: April 2010
Estimated Study Completion Date: December 2018
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Drug: Riociguat (Adempas, BAY63-2521)
up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg)
Experimental: Riociguat (Adempas, BAY63-2521) up to 1 mg
Participants received riociguat up to 1 mg tid (increasing from 0.5 to 1 mg).
Drug: Riociguat (Adempas, BAY63-2521)
up to 1 mg three times a day (increasing from 0.5 to 1 mg)
Experimental: Riociguat (Adempas, BAY63-2521) fixed 0.5 mg
Participants received riociguat 0.5 mg tid (fixed dose).
Drug: Riociguat (Adempas, BAY63-2521)
fixed 0.5 mg three times a day
Placebo Comparator: Placebo
Participants received placebo tid.
Drug: Placebo
Placebo three times a day

Detailed Description:

Pharmacokinetics parameters were regarded as exploratory parameters. Adverse event data will be covered in Adverse events section.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01065454

  Show 111 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01065454     History of Changes
Other Study ID Numbers: 14308, 2009-015878-35
Study First Received: February 8, 2010
Results First Received: November 6, 2013
Last Updated: September 23, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Denmark: Danish Medicines Agency
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Singapore: Health Sciences Authority
United States: Food and Drug Administration

Keywords provided by Bayer:
Pulmonary Hypertension
Left ventricular dysfunction

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Ventricular Dysfunction
Ventricular Dysfunction, Left
Cardiovascular Diseases
Heart Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014