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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01065454




Trial ID
NCT01065454
Ethics application status
Date submitted
8/02/2010
Date registered
8/02/2010
Date last updated
26/01/2018

Titles & IDs
Public title
A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction
Scientific 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
Secondary ID [1] 0 0
2009-015878-35
Secondary ID [2] 0 0
14308
Universal Trial Number (UTN)
Trial acronym
LEPHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension, Pulmonary 0 0
Ventricular Dysfunction, Left 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Placebo

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).

Experimental: Riociguat (Adempas, BAY63-2521) up to 1 mg - Participants received riociguat up to 1 mg tid (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).

Placebo Comparator: Placebo - Participants received placebo tid.


Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
up to 2 mg three times a day (increasing from 0.5 to 1 to 2 mg)

Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
up to 1 mg three times a day (increasing from 0.5 to 1 mg)

Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
fixed 0.5 mg three times a day

Treatment: Drugs: Placebo
Placebo three times a day

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
At visit 6 (16 weeks)
Secondary outcome [18] 0 0
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").
Timepoint [18] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [19] 0 0
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).
Timepoint [19] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [20] 0 0
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).
Timepoint [20] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [21] 0 0
Cystatin C - Change From Baseline to Week 16 - Cystatin C is a biomarker for predicting new onset or deteriorating cardiovascular disease.
Timepoint [21] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [22] 0 0
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.
Timepoint [22] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [23] 0 0
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.
Timepoint [23] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [24] 0 0
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.
Timepoint [24] 0 0
Baseline and visit 6 (16 weeks)
Secondary outcome [25] 0 0
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.
Timepoint [25] 0 0
Baseline and visit 6 (16 weeks)

Eligibility
Key inclusion criteria
- Male and female patients with symptomatic pulmonary hypertension due to left
ventricular systolic dysfunction despite optimized heart failure therapy
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Types of pulmonary hypertension other than group 2.1 of Dana Point Classification

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Chermside
Recruitment hospital [3] 0 0
- Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Austria
State/province [14] 0 0
Tirol
Country [15] 0 0
Austria
State/province [15] 0 0
Wien
Country [16] 0 0
Belgium
State/province [16] 0 0
Aalst
Country [17] 0 0
Belgium
State/province [17] 0 0
Bruxelles - Brussel
Country [18] 0 0
Belgium
State/province [18] 0 0
Gent
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
China
State/province [23] 0 0
Sichuan
Country [24] 0 0
China
State/province [24] 0 0
Beijing
Country [25] 0 0
China
State/province [25] 0 0
Shanghai
Country [26] 0 0
Czechia
State/province [26] 0 0
Brno
Country [27] 0 0
Czechia
State/province [27] 0 0
Olomouc
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha 2
Country [29] 0 0
Czechia
State/province [29] 0 0
Praha 4
Country [30] 0 0
Denmark
State/province [30] 0 0
Aarhus N
Country [31] 0 0
France
State/province [31] 0 0
Bron
Country [32] 0 0
France
State/province [32] 0 0
Lille Cedex
Country [33] 0 0
France
State/province [33] 0 0
Nantes
Country [34] 0 0
France
State/province [34] 0 0
Pessac
Country [35] 0 0
France
State/province [35] 0 0
Rouen
Country [36] 0 0
France
State/province [36] 0 0
Toulouse
Country [37] 0 0
Germany
State/province [37] 0 0
Baden-Württemberg
Country [38] 0 0
Germany
State/province [38] 0 0
Bayern
Country [39] 0 0
Germany
State/province [39] 0 0
Hessen
Country [40] 0 0
Germany
State/province [40] 0 0
Mecklenburg-Vorpommern
Country [41] 0 0
Germany
State/province [41] 0 0
Nordrhein-Westfalen
Country [42] 0 0
Germany
State/province [42] 0 0
Saarland
Country [43] 0 0
Germany
State/province [43] 0 0
Thüringen
Country [44] 0 0
Germany
State/province [44] 0 0
Berlin
Country [45] 0 0
Italy
State/province [45] 0 0
Campania
Country [46] 0 0
Italy
State/province [46] 0 0
Lombardia
Country [47] 0 0
Japan
State/province [47] 0 0
Aichi
Country [48] 0 0
Japan
State/province [48] 0 0
Gifu
Country [49] 0 0
Japan
State/province [49] 0 0
Hiroshima
Country [50] 0 0
Japan
State/province [50] 0 0
Ibaraki
Country [51] 0 0
Japan
State/province [51] 0 0
Mie
Country [52] 0 0
Japan
State/province [52] 0 0
Miyagi
Country [53] 0 0
Japan
State/province [53] 0 0
Nagasaki
Country [54] 0 0
Japan
State/province [54] 0 0
Osaka
Country [55] 0 0
Japan
State/province [55] 0 0
Saga
Country [56] 0 0
Japan
State/province [56] 0 0
Saitama
Country [57] 0 0
Japan
State/province [57] 0 0
Shiga
Country [58] 0 0
Japan
State/province [58] 0 0
Shizuoka
Country [59] 0 0
Japan
State/province [59] 0 0
Tokyo
Country [60] 0 0
Japan
State/province [60] 0 0
Wakayama
Country [61] 0 0
Netherlands
State/province [61] 0 0
Amsterdam
Country [62] 0 0
Netherlands
State/province [62] 0 0
Nijmegen
Country [63] 0 0
Poland
State/province [63] 0 0
Bydgoszcz
Country [64] 0 0
Poland
State/province [64] 0 0
Gdansk
Country [65] 0 0
Poland
State/province [65] 0 0
Lodz
Country [66] 0 0
Poland
State/province [66] 0 0
Warszawa
Country [67] 0 0
Singapore
State/province [67] 0 0
Singapore
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Spain
State/province [69] 0 0
Murcia
Country [70] 0 0
Spain
State/province [70] 0 0
Palma De Mallorca
Country [71] 0 0
Spain
State/province [71] 0 0
A Coruña
Country [72] 0 0
Spain
State/province [72] 0 0
Barcelona
Country [73] 0 0
Spain
State/province [73] 0 0
Sevilla
Country [74] 0 0
Spain
State/province [74] 0 0
Valencia
Country [75] 0 0
Sweden
State/province [75] 0 0
Göteborg
Country [76] 0 0
Switzerland
State/province [76] 0 0
Ticino
Country [77] 0 0
Switzerland
State/province [77] 0 0
Genève
Country [78] 0 0
Switzerland
State/province [78] 0 0
Zürich
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Cambridge
Country [80] 0 0
United Kingdom
State/province [80] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT01065454
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries