Pulmonary hypertension and heart failure with preserved ejection fraction
Conditions
Interventions
Trade Name: Adempas
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIOCIGUAT
CAS Number: 625115-55-1
Current Sponsor code: RIO-40400
Other descriptive name: RIOCIGUAT
Concentration unit:
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must fulfill the following criteria to be eligible for this study: - 18 to 15 mmHg at rest, measured by RHC - Optimized therapy for hypertension - The dose regimen of the background treatment must have been stable for >30 days before randomization. Diuretic therapy must have been stable for =1 week. - RHC results for the definite diagnosis of PH not older than 12 weeks at Visit 1. RHC must have been performed in the participating center under standardized conditions (refer to the study-specific Swan-Ganz catheterization manual). - CMRI must be performed at Visit 1 (baseline) or must not be older than 12 weeks with all parameters measured as listed in Section 7.3.3 of the protocol - 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 serum 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 entire duration of the study - Men enrolled in this study must agree to use adequate barrier birth control measures during the treatment period of the study and inform their sexual partners during the study period and three months beyond their study participation about the possibility of foetal impairment. - Able to understand and follow instructions and to participate in the study for its entire duration - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: - PH in groups other than group 2.2 according to Dana Point classification - Cardiac decompensation, with hospitalization or visit to the emergency department, =30 days before randomization - Left heart disease because of to ischemic heart disease or dilated cardiomyopathy - Resynchronization therapy at any time - Need for intravenous (IV) diuretics =30 days before randomization - Treatment with inotropes or IV vasodilators =30 days before randomization - Pre-treatment with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 (PDE5) inhibitors, or prostanoids =30 days before randomization, or with nitrates =7 days before randomization - 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 of study protocol) for this study - Bronchial asthma or chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) 180 mmHg or diastolic blood pressure [DBP] >110 mmHg) - SBP 105 BPM (in case of atrial fibrillation >110 BPM) - Participation in another clinical study <90 days before randomization - 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 26-week study - Subjects with underlying medical disorders with an anticipated life expectancy below 2 years because of a non-cardiac disease (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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to - Assess the pharmacodynamic profile of riociguat in subjects with symptomatic pulmonary hypertension and heart failure with preserved ejection fraction;Secondary Objective: The secondary objectives of this study are to - Assess safety and tolerability of riociguat in this study population - Assess changes in dimensions of left and right ventricles and cardiac function parameters using cardiac magnetic resonance imaging;Primary end point(s): Change from baseline of cardiac output (CO) at rest, measured by right heart catheter (RHC);Timepoint(s) of evaluation of this end point: Baseline and after 26 weeks of study drug treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in left atrial area, right ventricular volume, and right ejection fraction, measured by CMRI - Change from baseline in PVR, SVR, TPG, and PAWP, measured by RHC - Change from baseline in WHO class - Change from baseline in cardiac biomarkers NT-pro BNP;Timepoint(s) of evaluation of this end point: Baseline and after 26 weeks of study drug treatment | — |
Countries
Austria, Germany
Contacts
Public ContactStudy Team Prof. Bonderman
Medical University of Vienna
Outcome results
None listed