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Placebo-controlled, multi-center study to evaluate catheter derived tests of Riociguat (BAY 63-2521) as well as safety and blood samples in patients with pulmonary hypertension associated with left heart failure.
EU CTIS ID: 2023-507001-34-00
What this study is testing
The primary objective of this study is to assess the hemodynamic profile of Riociguat in patients with symptomatic pulmonary hypertension associated with left ventricular systolic dysfunction (PH-sLVD).
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 18 to 80 years of age at the time of informed consent (The lower age limit may be higher if legally required in participating countries.)
- Male and female subjects with symptomatic PH-sLVD (group 2 / 2.1 of Dana Point Classification and World Health Organization [WHO] class II-IV) due to ischemic heart disease or dilated cardiomyopathy (DCM). Transplant candidates can be included. (Other groups of pulmonary hypertension, especially CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2 Exclusion criteria.) PH-sLVD is defined as: - LVEF ≤ 40%, diagnosed by echocardiography, radionuclide ventriculography or left heart catheter (LHC) exam within 30 days before randomization, or in the baseline echocardiography (Note: the definition of PH-sLVD was changed in amendment 3 see section 13.2.1.2) - PAPmean ≥ 25 mmHg at rest, measured by right heart catheter (RHC)
- Subjects must be pre treated and individually maximally titrated with optimized CHF therapy according to European Society of Cardiology (ESC) (9), American College of Cardiology/American Heart Association (ACC/AHA) (10) or Japanese Circulation Society (11) guidelines with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta blockers and mineralocorticoid receptor (MR) antagonists as clinically indicated. The dose regimen must have been stable for > 30 days prior to randomization. Diuretic therapy must have been stable for ≥ 1 week before performing baseline RHC.
- RHC results for the definite diagnosis of PH not older than 1 week at Visit 1. RHC must have been performed in the participating centre under standardized conditions (refer to the study specific right heart catheterization manual).
- Left heart catheter results available any time prior to randomization to judge if left-heart disease is caused by ischemic heart disease or dilated cardiomyopathy
- A negative stress test must have been performed < 1 year prior to randomization according to guidelines (stress electrocardiography [ECG], stress echocardiography, stress scintigraphy) to exclude overt or silent ischemia.
You likely can't join if
- PH in groups other than group 2.1 according to Dana Point classification (2). In particular, CTEPH must have been ruled out according to accepted diagnostic procedures and guidelines.
- Subjects on O2 therapy
- Severe congenital abnormalities of the lungs, thorax or diaphragm
- Clinically relevant hepatic dysfunction indicated by either: - aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal (ULN) - Child Pugh stage B and C in cirrhotic patients.
- Severe renal impairment (glomerular filtration rate [GFR] < 30 mL/min calculated by Modification of Diet in Renal Disease [MDRD] formula)
- Uncontrolled arterial hypertension (systolic blood pressure [SBP] > 180 mmHg or diastolic blood pressure [DBP] > 110 mmHg)
See the full eligibility criteria
Who can join
- 18 to 80 years of age at the time of informed consent (The lower age limit may be higher if legally required in participating countries.)
- Male and female subjects with symptomatic PH-sLVD (group 2 / 2.1 of Dana Point Classification and World Health Organization [WHO] class II-IV) due to ischemic heart disease or dilated cardiomyopathy (DCM). Transplant candidates can be included. (Other groups of pulmonary hypertension, especially CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2 Exclusion criteria.) PH-sLVD is defined as: - LVEF ≤ 40%, diagnosed by echocardiography, radionuclide ventriculography or left heart catheter (LHC) exam within 30 days before randomization, or in the baseline echocardiography (Note: the definition of PH-sLVD was changed in amendment 3 see section 13.2.1.2) - PAPmean ≥ 25 mmHg at rest, measured by right heart catheter (RHC)
- Subjects must be pre treated and individually maximally titrated with optimized CHF therapy according to European Society of Cardiology (ESC) (9), American College of Cardiology/American Heart Association (ACC/AHA) (10) or Japanese Circulation Society (11) guidelines with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta blockers and mineralocorticoid receptor (MR) antagonists as clinically indicated. The dose regimen must have been stable for > 30 days prior to randomization. Diuretic therapy must have been stable for ≥ 1 week before performing baseline RHC.
- RHC results for the definite diagnosis of PH not older than 1 week at Visit 1. RHC must have been performed in the participating centre under standardized conditions (refer to the study specific right heart catheterization manual).
- Left heart catheter results available any time prior to randomization to judge if left-heart disease is caused by ischemic heart disease or dilated cardiomyopathy
- A negative stress test must have been performed < 1 year prior to randomization according to guidelines (stress electrocardiography [ECG], stress echocardiography, stress scintigraphy) to exclude overt or silent ischemia.
- Women are eligible if not of childbearing potential, defined as: - postmenopausal women (i.e. last menstrual bleeding at least 2 years before randomization) - women with bilateral tubal ligation - women with bilateral ovariectomy - women with hysterectomy or, if of childbearing potential, women are eligible if - a serological pregnancy test is negative at the pre-study visit, and - the woman uses a combination of condoms and a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices) for the duration of the study.
- Subject is able to understand and follow instructions and is able to participate in the study for the entire period
- Written informed consent.
What rules you out
- PH in groups other than group 2.1 according to Dana Point classification (2). In particular, CTEPH must have been ruled out according to accepted diagnostic procedures and guidelines.
- Subjects on O2 therapy
- Severe congenital abnormalities of the lungs, thorax or diaphragm
- Clinically relevant hepatic dysfunction indicated by either: - aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal (ULN) - Child Pugh stage B and C in cirrhotic patients.
- Severe renal impairment (glomerular filtration rate [GFR] < 30 mL/min calculated by Modification of Diet in Renal Disease [MDRD] formula)
- Uncontrolled arterial hypertension (systolic blood pressure [SBP] > 180 mmHg or diastolic blood pressure [DBP] > 110 mmHg)
- SBP < 100 mmHg at baseline or clinical signs or symptoms of hypotension (Note: limit changed and additional text added in amendment 3 see section 13.2.1.3)
- Myocardial disease other than ischemic or dilatative, such as infiltrative myocardial disease (i.e. amyloidosis, hypertrophic cardiomyopathy)
- Severe aortic or mitral stenosis, or any such stenosis with indication for surgery
- Coronary artery disease with angina of Canadian Cardiovascular Society (CCS) class III or IV or requiring nitrates, unstable angina, or acute myocardial infarction less than 90 days prior to randomization
- Reperfusion procedure (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) less than 90 days prior to randomization, or less than 3 weeks in case of a negative stress test after PCI
- Cardiac decompensation, either with hospitalization or visit to the emergency department, ≤ 30 days prior to randomization
- Stroke with persistent neurological deficit or known hemodynamically relevant symptomatic carotid artery stenosis
- Subjects positive for human immunodeficiency virus (HIV)
- Resting heart rate (HR) while awake of < 50 beats per minute (BPM) or > 105 BPM (in case of atrial fibrillation > 110 BPM)
- Investigational treatment in another clinical trial during the preceding 30 days
- Subjects with a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the subject's ability to participate or complete the 4 month main study
- Subjects with underlying medical disorders with an anticipated life expectancy below 2 years not due to cardiac conditions (e.g. active cancer disease with localized and/or metastasized tumor mass)
- Subjects with a history of multiple drug allergies
- Subjects with hypersensitivity to the investigational drug or any of the excipients
- Previous assignment to treatment during this study.
- Resynchronization therapy initiated ≤ 90 days prior to randomization
- Need of intravenous (IV) diuretics ≤ 30 days prior to randomization
- Treatment with IV inotropes or IV vasodilators ≤ 30 days prior to randomization
- Chronic treatment with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 (PDE5) inhibitors or prostanoids ≤ 30 days prior to randomization, or with nitrates ≤ 7 days prior to randomization (PDE5 inhibitors ≤ 7 days prior to randomization if indicated for erectile dysfunction)
- Subjects who medically require treatment with drugs that are not in line with the in or exclusion criteria of this study or that are prohibited concomitant medications (see section 6.9) for this study
- Bronchial asthma or chronic obstructive pulmonary disease (COPD) with forced expiratory volume in one second (FEV1) < 60% of predicted
- Restrictive lung disease with total lung capacity (TLC) < 60% of predicted
The study team makes the final eligibility decision.
Where it's taking place
- Switzerland
- United States
- Australia
- United Kingdom
- Japan
- China
- Singapore
- Canada
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Switzerland; United States; Australia; United Kingdom; Japan; China and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.