Riociguat single -dose study measuring of blood flow in lungs with high blood pressure associated with heart failure.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 48

Inclusion Criteria

Patients must fulfill all of the following criteria before being included in the study:
1.Age = 18 years
2.Invasive confirmation of PH associated with DHF documented by right heart catheter measurements of the following parameters:
•PAPmean = 25 mmHg and
•PCWP =15 mmHg
3.Transthoracic echocardiography
•confirming preserved ejection fraction with LVEF>50% and
•evidence for diastolic dysfunction,
-either abnormal relaxation (E/A wave ratio <1) or
-diastolic stiffness (E/A-wave ratio >2, E-wave deceleration time <115-150 ms)
4.NYHA class >I
5.Serum NT-proBNP >400 pg/ml
6.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 38

Exclusion Criteria

General exclusion criteria:
1.Previous assignment to treatment during this study
2.Participation in another clinical trial during the preceding 3 months.
3.Pregnant women, or breast feeding women, or women with childbearing potential not using a combination of condoms and a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices [IUDs]).
4.Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator.
5.Patients with a history of severe allergies or multiple drug allergies.
6.Known hypersensitivity to study drug or any of the excipients
Medication/Treatment exclusion criteria:
1.Pre-Treatment within 30 days before randomization with:
•intravenous (IV) inotropes or IV vasodilators
•endothelin receptor antagonists (ERAs), PDE5 inhibitors or prostanoids.
2.Treatment within 7 days before randomization with NO donors (e.g. nitrates).
3.Requirement of treatment with prohibited drugs (see section 6.9) within 48 h after study drug intake.
Pulmonary diseases exclusion criteria:
1.Bronchial asthma or COPD with Forced Expiratory Volume in one second (FEV1) <60% predicted.
2.Restrictive lung disease with Total Lung Capacity <60% predicted.
3.Severe congenital abnormalities of the lungs, thorax, or diaphragm.
4.O2 therapy
5.Clinical or radiological evidence of Pulmo-Veno-Occlusive Disease (PVOD) or Pulmonary Capillary Hemangiomatosis (PCH).
Exclusion criteria related to abnormalities in blood gases (measured capillary or arterial):
1.SaO2 < 88%
2.PaO2 < 55 mmHg
Cardiovascular exclusion criteria:
1.Pulmonary hypertension of groups other than 2.2 of Dana Point Classification
2.Significant valvular heart disease apart from tricuspid valvular insufficiency due to PH
3.Presence of angina pectoris of Canadian Cardiovascular Society Classification class 3 to 4 and/or requiring nitrates, unstable angina, or myocardial infarction within the last 3 months.
4.Hypertrophic cardiomyopathy, amyloidosis, or cardiomyopathy associated with storage disease
5.Constrictive pericarditis
6.Resting heart rate while awake <50 bpm or >110 bpm
7.Uncontrolled arterial hypertension (Systolic blood pressure >180 mmHg and /or diastolic blood pressure >110 mmHg) or arterial hypertension not optimally treated according to current guidelines [10].
8.Systolic blood pressure <95 mmHg.
Exclusion criteria related to disorders in organ function:
1.Clinically relevant hepatic dysfunction indicated by either:
•Aspartate aminotransferase (AST) >3 times upper limit normal (ULN)
•Child Pugh stage B and C in cirrhotic patients
2.Severe chronic renal insufficiency (glomerular filtration rate [GFR] GFR <30 mL/min calculated by Modification of Diet in Renal Disease [MDRD] formula).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of the present study is to evaluate the acute hemodynamic effects, safety, and pharmacokinetics of Riociguat in patients with PH associated with diastolic heart failure.;Secondary Objective: ;Primary end point(s): The primary efficacy variable is the peak decrease from baseline in mean pulmonary arterial pressure (PAPmean).

Secondary Outcome Measures

Name	Time	Method

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