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

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ClinicalTrials.gov Identifier: NCT01065454
Recruitment Status : Active, not recruiting
First Posted : February 9, 2010
Results First Posted : December 25, 2013
Last Update Posted : March 5, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE February 8, 2010
First Posted Date  ICMJE February 9, 2010
Results First Submitted Date  ICMJE November 6, 2013
Results First Posted Date  ICMJE December 25, 2013
Last Update Posted Date March 5, 2021
Actual Study Start Date  ICMJE April 14, 2010
Actual Primary Completion Date June 6, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2010)
Pulmonary artery mean pressure at rest [ Time Frame: Change from baseline after 16 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2013)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2010)
  • Adverse event collection [ Time Frame: Until week 16 + 4 weeks Follow-up ]
  • Pharmacokinetic profile of Riociguat [ Time Frame: Until week 16 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypertension, Pulmonary
  • Ventricular Dysfunction, Left
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 21, 2020)
202
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2010)
180
Estimated Study Completion Date  ICMJE December 31, 2023
Actual Primary Completion Date June 6, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   China,   Czechia,   Denmark,   France,   Germany,   Italy,   Japan,   Netherlands,   Poland,   Singapore,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT01065454
Other Study ID Numbers  ICMJE 14308
2009-015878-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, time point and process of data access. As such, Bayer commits to sharing upon request from qualified researcher's 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date March 2021

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