Hypertension, Pulmonary, Heart Failure With Normal Ejection Fraction
Conditions
Keywords
PH-HFpEF
Brief summary
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 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
Interventions
DRUGRiociguat
Adempas up-titrated to max. 1.5mg TID
DRUGPlacebo
Placebo sham-titrated TID
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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 and HF-PEF (group 2 / 2.2 of Dana Point classification(4) and WHO class II to IV) (Other groups of PH, especially HF-REF, PAH, CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2
Exclusion criteria
.) * PH-HF-PEF defined as: * LVEF ≥50%, diagnosed by echocardiography or left heart catheterization (LHC) within 30 days before randomization * PAPmean ≥25 mmHg at rest, measured by RHC * PAWP \>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 * 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 * 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. * Able to understand and follow instructions and to participate in the study for its entire duration * Written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of cardiac output at rest, measured by right heart catheterization | Baseline and 26 weeks after study drug treatment | Change from baseline of cardiac output at rest, measured by right heart catheterization after 26 weeks of study drug treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in cardiac magnetic resonance imaging parameters | Baseline and 26 weeks after study drug treatment | Change from baseline in right ventricular ejection fraction by cardiac magnetic resonance imaging |
| Change from baseline in hemodynamic parameters other than cardiac output | Baseline and 26 weeks after study drug treatment | Change from baseline in pulmonary vascular resistance by right heart catheterization |
| Change from baseline in WHO functional class | Baseline and 26 weeks after study drug treatment | — |
| Change from baseline in biomarker levels | Baseline and 26 weeks after study drug treatment | Change from baseline in serum N-terminal prohormone B-type natriuretic peptide (NTproBNP) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in quality of life scores: MLHF | Baseline and 26 weeks after study drug treatment | — |
| Events of special interest | Baseline and 26 weeks after study drug treatment | Events of special interest considered for calculation of the combined endpoint time to clinical worsening |
| Change from baseline in T1-mapping parameters by CMR | Baseline and 26 weeks after study drug treatment | Change from baseline in native T1 times of the left ventricular myocardium |
| Composite endpoint | Baseline and 26 weeks after study drug treatment | Composite endpoint as defined by: time to death from cardiovascular causes or first hospitalization for a cardiovascular event, including acute or worsening heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia |
| All-cause mortality | Baseline and 26 weeks after study drug treatment | — |
| Change from baseline in echocardiography parameters | Baseline and 26 weeks after study drug treatment | Change from baseline in left ventricular end-systolic volume by echocardiography |
| Change from baseline in exercise capacity: 6-minute walk distance | Baseline and 26 weeks after study drug treatment | — |
| Change from baseline in exercise capacity: Borg CR 10 scale | Baseline and 26 weeks after study drug treatment | — |
| Change from baseline in quality of life scores: EQ-5D | Baseline and 26 weeks after study drug treatment | — |
Countries
Austria
Outcome results
None listed