Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH. (CHEST-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00855465
First received: December 15, 2008
Last updated: October 24, 2014
Last verified: October 2014

December 15, 2008
October 24, 2014
February 2009
June 2012   (final data collection date for primary outcome measure)
6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.
6 Minute Walking Distance [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00855465 on ClinicalTrials.gov Archive Site
  • Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ 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
  • N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    N-terminal pro-brain natriuretic peptide (NT-proBNP) 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.
  • World Health Organization (WHO) Functional Class - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ 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 week 16 ] [ 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; heart/lung transplantation; rescue endarterectomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH.
  • Borg CR 10 Scale - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. 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 week 16 ] [ Designated as safety issue: No ]
    EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).
  • Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst).
  • Change from baseline in Pulmonary Vascular Resistance (PVR) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in NT-pro BNP [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in WHO functional class [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Borg Dyspnoea Score [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Time to clinical worsening [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in EQ-5D and LPH. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Safety variables: adverse events, laboratory parameters, ECG, vital signs. [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • All Caused Mortality [ Time Frame: At visit 6 (week 16) ] [ Designated as safety issue: Yes ]
    All cause mortality (including cardiovascular mortality) was one component of the composite endpoint "time to clinical worsening".
  • Mean Pulmonary Artery Pressure (PAPmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.
  • Cardiac Index (CI) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The cardiac index (CI) is a calculated hemodynamic parameter. CI is derived from the directly measured parameters cardiac output (CO), divided by the body surface area (BSA). BSA is a calculated parameter, using the subject's height and weight in the DuBois formula. Formula: BSA = (W [kg]*0.425)*(H [cm]*0.725)*0.007184 (m^2)
  • Systolic Blood Pressure (SBP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Systolic systemic arterial blood pressure (SBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 95 - 180 mmHg.
  • Diastolic Blood Pressure (DBP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Diastolic systemic arterial blood pressure (DBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: <= 110 mmHg.
  • Heart Rate (HR) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Heart rate (HR) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 50 -105 beats per minute (bpm) at rest.
  • Alanine Aminotransferase (ALT) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Alanine Aminotransferase (ALT) is a standard clinical chemistry parameter. Normal range: 0 to 45 U/L.
  • Aspartate Aminotransferase (AST) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Aspartate Aminotransferase (AST) is a standard clinical chemistry parameter. Normal range: 0 to 41 U/L.
  • Alkaline Phosphatase (AP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Alkaline phosphatase (AP) is a standard clinical chemistry parameter. Normal range: 40 to 129 U/L (males), 35 to 104 U/L (females)
  • Bilirubin - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Bilirubin is a standard clinical chemistry parameter. Normal range: 0.1 to 1.2 mg/dL
  • Creatinine - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Creatinine is a standard clinical chemistry parameter. Normal range: 0.25 to 1.20 mg/dL (males), 0.46 to 1.00 mg/dL (females)
  • Creatinine Clearance - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Creatinine clearance is a standard clinical chemistry parameter. Normal range: 90 to 140 mL/min (males), 80 to 125 mL/min (females)
  • Creatine Kinase (CK) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Creatine Kinase is a standard clinical chemistry parameter. Normal range: 35 to 232 U/L (males), 26 to 145 U/L (females)
  • Erythrocytes (RBC) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Erythrocytes (red blood cells, RBC) is a standard clinical hematology parameter. Normal range: 4.6 to 5.8*10^12 cells/L (males), 4.1 to 5.2*10^12 cells/L (females)
  • Leukocytes (WBC) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Leukocytes (white blood cells, WBC) is a standard clinical hematology parameter. Normal range: 4.0 to 10.7*10^9 cells/L
  • Lymphocytes - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Total lymphocytes is a standard clinical hematology parameter. Normal range: 1.0 to 4.0*10^9 cells/L
  • Neutrophils - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Neutrophils is a standard clinical hematology parameter. Normal range: 1.6 to 7.4*10^9 cells/L
  • Hemoglobin - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Hemoglobin is a standard clinical hematology parameter. Normal range: 13.5 to 17.5 g/dL (males), 12.0 to 16.0 g/dL (females)
  • Hematocrit - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Hematocrit is a standard clinical hematology parameter. Normal range: 40 to 52% (males), 36 to 46% (females)
  • Potassium - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Potassium is a standard clinical chemistry parameter. Normal range: 3.5 to 5.3 mmol/L
  • Urate - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Urate is a standard clinical chemistry parameter. Normal range: 4.0 to 8.5 mg/dL (males, 16-59 years), 3.4 to 8.7 mg/dL (males, >60 years) 2.5 to 7.5 mg/dL (females)
  • Urea (BUN) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Urea (blood urea nitrogen, BUN) is a standard clinical chemistry parameter. Normal range: 4 to 25 mg/dL
  • Cystatin C - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Cystatin C is a biomarker. Normal range: 0.53 to 1.01 ng/mL
  • Triacylglycerol Lipase - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Triacylglycerol lipase is a standard clinical chemistry parameter. Normal range: 7 to 60 U/L
  • Arterial Partial Pressure of Carbon Dioxide (PaCO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Arterial partial pressure of carbon dioxide (PaCO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.
  • Arterial Partial Oxygen Pressure (PaO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Arterial partial pressure of oxygen (PaO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.
  • Oxygen Saturation (SaO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Oxygen saturation (SaO2) is measured as part of the capillary or arterial blood gas analysis. Normal blood oxygen saturation is considered 95-100 percent. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.
  • Mean PR Duration (PRmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    PR duration was evaluated as part of the 12-lead electrocardiogram. electrocardiograms (ECGs) were recorded after the participant had been at rest for 15 minutes in a supine position.
  • Mean QRS Duration (QRSmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    QRS duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
  • Mean QT Duration (QTmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    QT duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
  • Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Bazett-corrected QTcB duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
  • Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Fridericia-corrected QTcF duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
  • Mean RR Duration (RRmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    RR duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
  • Mean Ventricular Rate (VRmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Ventricular rate was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position
Not Provided
 
A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH.
Randomized, Double-blind, Placebo-controlled, Multi-centre, Multi-national Study to Evaluate the Efficacy and Safety of Oral BAY63-2521 (1 mg, 1.5 mg, 2 mg, or 2.5 mg Tid) in Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521, given orally for 16 weeks, in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Adverse event data will be covered in Adverse events section.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Pulmonary Hypertension
  • Drug: Riociguat (Adempas, BAY63-2521)
    BAY63-2521: 1 mg tid - 2,5 mg tid orally for 16 weeks.
  • Drug: Placebo
    Matching Placebo tid orally for 16 weeks
  • Experimental: Riociguat (Adempas, BAY63-2521)_individual dose titration
    Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks
    Intervention: Drug: Riociguat (Adempas, BAY63-2521)
  • Placebo Comparator: Placebo
    Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
262
June 2012
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male and female patients with CTEPH either inoperable or with persistent or recurrent PH after surgery.

Exclusion Criteria:

  • All types of pulmonary hypertension except subtypes 4.1 and 4.2 of the Venice Clinical Classification of Pulmonary Hypertension.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Czech Republic,   Denmark,   France,   Germany,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Portugal,   Russian Federation,   Slovakia,   Spain,   Switzerland,   Taiwan,   Turkey,   United Kingdom
 
NCT00855465
11348, 2007-000072-16
Yes
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
October 2014

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