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

• Conditions: Pulmonary hypertension associated with diastolic heart failure; MedDRA version: 13.1Level: LLTClassification code 10037405Term: Pulmonary hypertension primarySystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

• Registration Number: EUCTR2010-018436-41-AT
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-22
• Last Update Posted: 11 February 2013

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

o in patients with sinus rhythm: either abnormal relaxation (E/A wave ratio <1) or diastolic stiffness (E/A-wave ratio >2)
or
o in patients with atrial fibrillation: E-wave deceleration time <150 ms
4. NYHA class >I
5. Serum NT-proBNP >220 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 30 days.

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 defined by the requirement for surgical repair apart from tricuspid valvular insufficiency due to PH.

3.Presence of myocardial ischemia as indicated by angina pectoris, stress test, or coronary angiography.

4.Unstable angina or myocardial infarction within the last 3 months.

5. Revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery
bypass graft [CABG]) within the last 3 months.

6. Cardiac surgery within the last 3 months, or transcatheter aortic valve implantation within
30 days, or ongoing prolonged hospitalization after cardiac surgery.

7. Clinical instability with cardiac decompensation or clinical constellation at the time of randomization, characterized by any of the following:

a. Pleural or pericardial effusion requiring pleura- / pericardiocentesis
b. Need for IV diuretic treatment or evidence for volume overload

c. Admission to emergency or intensive care unit

d. Need for non-study procedures including stress testing or contrast media exposure that could confound the results and stress the patient

8. Critical carotid artery stenosis

9. Hypertrophic cardiomyopathy, amyloidosis, or cardiomyopathy associated with storage disease

10. Constrictive pericarditis

11. Resting heart rate while awake <50 bpm or >110 bpm

12. Uncontrolled arterial hypertension (Systolic blood pressure >180 mmHg and /or diastolic blood pressure >110 mmHg) or arterial hypertension not optimally managed according to current guidelines and requiring immediate antihypertensive treatment.

Exclusion criteria related to disorders in organ function:
1.Clinically r

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).