Heart failure with normal left ventricle systolic function (HFNEF) are common causes of hospitalisation mainly in the elderly population and are frequently associated with pulmonary hypertension. It is commonly seen, that patients with left heart disease and pulmonary hypertension with right ventricle dysfunction have a worse prognosis. The medical condition to be investigated is HFNEF (Ejection fraction > 50%) and secondary pulmonary hypertension. MedDRA version: 9.1 Level: LLT Classification
Conditions
Interventions
Trade Name: Tracleer
Product Name: Bosentan (Tracleer)
Product Code: Ro 47.0203
Pharmaceutical Form: Capsule*
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral
Sponsors
Universitätslehrkrankenhaus Hall in Tirol
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Screening phase a) Clinically signs or history of congestive heart failure NYHA II-III: (Fatigue, dyspnoea on excertion, lung crepitations, pulmonary oedema, ankle and or lower leg swelling, jugular pressure enhancement, hepatomegaly) b) Echocardiographic signs of diastolic dysfunction: Echocardiographic requirements for definition of heart failure with normal ejection fraction ? E/E` > 15 ? E/E` > 8 + NTpBNP > 220 pg/dl ? E/E` > 8 + E:A 280 ms or Ard-Ad > 30 ms or atrial enlargement or atrial fibrillation ? NTpBNP > 220 + combination 3.) ? IVRT – IVRTm 30 mm short axis parasternal, and one of the following ? Tricuspid valve regurgitation velocity (TRV) > 3 m/s; ? RV-anular systolc velocity 150 m 25 mmHg ? PCWP > 15 mmHg 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who are not on guideline conform treatments for cardio-vascular disease. Left ventricle systolic dysfunction (EF 40 mm Hg, moderate and severe mitral regurgitation, acute coronary disease, stable coronary artery disease or peripheral vascular disease limiting exercise. Other causes of pulmonary – artery – hypertension: relevant obstructive ventilatory disease > stage II (lung function tests for obstructive ventilation disturbances) collagen disease (Tests: MSCT and ANA, ANCA), chronic thrombo- embolic pulmonary arterial hypertension (MSCT), sleep disorder. HIV, HCV, HBV infection. Drug related PAH. Orthopaedic disease, immobility, inability to perform 6MWT and cancer. Liver disease Child-Pugh B and C, three fold above normal elevated liver enzymes, anaemia Hb < 10 mg/dl, drug therapy with cyclosporine A , tacrolimus, Sirolimus, Rifampicin and Glibenclamide; other specific therapies treating pulmonary hypertension, known adverse reactions to bosentan and pregnancy. Patients with child bearing potential need to be tested for pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Change on exercise capacity in patients with heart failure due to diastolic dysfunction (HFNEF > 50%) and secondary pulmonary hypertension (pulmonary venous hypertension – PVH) who are under guideline conform therapy of left ventricle dysfunction and additionally are treated with bosentan or placebo.;Secondary Objective: a) combined endpoint of clinical worsening ( death, re-hospitalisation, drug intervention because of clinically worsening, symptomatic worsening) b) Hemodynamics accessed by echocardiography in a 3 and 6 months follow up periode c) Laboratory testing: change in NTpBNP, C-reactive protein and Endothelin-1 d) safety of the intake of Bosentan;Primary end point(s): Change in 6 Minute Walk Test after 12 weeks of Bosentan medication Secondary end points: Clinical, laboratory and physical parameters a) NYHA classification after 3 and 6 months in comparison to the screening phase b) Borg Index (after 3 and 6 months) c) Quality of life SF 36 / Minnesota living with heart failure score (3 and 6 months) d) Echocardiography: Echocardiographic assessments at 3 and 6 months in contrast to the begining of the study (EF, E:E`, E:A, DT, Ard, Ad, LA-diameter, IVRT - IVRTm RV-diameter, excentricity index, TAPSE, RV-anular systolc velocity, TR-gradient and assumed systolic right ventricular pressure) e) Exercise capacity 6MWT after 6 months. f) Measurements of clinical worsening (Death, or Rehospitalisation because of clinically worsening, or Drug intervention because of clinically worsening, or Symptomatic worsening defined as: Appearance or worsening in heart failure, or Decline of 6 MWD = 10% in two tests within two weeks, or Decline of 6 MWD = 5 % in two tests within two weeks additionally to increasing Borg Index = 2) g) explorative end points: NTpBPN, C-reactive protein, Endothelin-1 after 3 and 6 months h) safety end-points: appearance and number of Adverse Events/ severe Adverse Events | — |
Countries
Austria
Outcome results
None listed