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

Hypertension, Pulmonary Clinical Trial

— LEPHT  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01065454
• Other study ID #: 14308
• Secondary ID: 2023-507001-34-0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 14, 2010
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 202
• Est. completion date: December 31, 2025
• Est. primary completion date: June 6, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Drug:
• Riociguat (Adempas, BAY63-2521)
up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg)
• Riociguat (Adempas, BAY63-2521)
up to 1 mg three times a day (increasing from 0.5 to 1 mg)
• Riociguat (Adempas, BAY63-2521)
fixed 0.5 mg three times a day
• Placebo
Placebo three times a day

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Singapore,  Spain,  Switzerland,  United Kingdom, 

References & Publications (2)

Bonderman D, Ghio S, Felix SB, Ghofrani HA, Michelakis E, Mitrovic V, Oudiz RJ, Boateng F, Scalise AV, Roessig L, Semigran MJ; Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group. Riociguat for — View Citation

Ghio S, Bonderman D, Felix SB, Ghofrani HA, Michelakis ED, Mitrovic V, Oudiz RJ, Frey R, Roessig L, Semigran MJ. Left ventricular systolic dysfunction associated with pulmonary hypertension riociguat trial (LEPHT): rationale and design. Eur J Heart Fail. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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	Baseline and visit 6 (16 weeks)
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	Baseline and visit 6 (16 weeks)
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	Baseline and visit 6 (16 weeks)
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	Baseline and visit 6 (16 weeks)
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	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	At visit 6 (16 weeks)
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").	Baseline and visit 6 (16 weeks)
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).	Baseline and visit 6 (16 weeks)
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).	Baseline and visit 6 (16 weeks)
Secondary	Cystatin C - Change From Baseline to Week 16	Cystatin C is a biomarker for predicting new onset or deteriorating cardiovascular disease.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)
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.	Baseline and visit 6 (16 weeks)