Safety and Efficacy of Bosentan in Patients With Diastolic Heart Failure and Secondary Pulmonary Hypertension (BADDHY)
Recruitment status was Recruiting
Heart failure is a major medical and socioeconomic problem in western industrial countries, especially with aging populations. Heart failure with normal left ventricle systolic function (heart failure with preserved ejection fraction, HFPEF, heart failure with normal ejection fraction, HFNEF) are common causes of hospitalization 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 investigators hypothesize, that an additional treatment with Bosentan in this patients will improve their exercise capacity, symptoms, hemodynamics and quality of life.
Heart Failure, Diastolic
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Endothelin Receptor Blockade in Heart Failure With Diastolic Dysfunction and Pulmonary Hypertension|
- change in 6 minute waling distance after 12 weeks of bosentan (or placebo) treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- change in 6 minute walking distance after 24 weeks (12 weeks bosentan or placebo treatment and 12 weeks follow-up) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- changes in hemodynamics assessed by echocardiography after 12 and 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- time to clinical worsening after 12 and 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- levels of NTpBNP, CRP and Endothelin-1 after 12 and 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Quality of Life assessment (SF-36 and Minnesota Living With Heart Failure Score) after 12 and 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- Adverse event count after 12 and 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2009|
|Estimated Study Completion Date:||April 2011|
|Estimated Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Active Comparator: bosentan
Patients in this arm receive bosentan twice a day for 12 weeks
4 weeks of oral bosentan 62,5 mg b.i.d., followed by 8 weeks of 125 mg b.i.d.
Placebo Comparator: placebo
patients in this arm receive 12 placebo twice a day for 12 weeks
placebo twice a day for 12 weeks
Heart Failure with preserved ejection fraction is with more than 50% of cases the most common form of heart failure. Typically patients are elderly women with arterial hypertension. Mortality, hospitalization rates due to heart failure and in-hospital complications do not differ significantly from patients with systolic heart failure. However there are some subgroups of HFPEF-patients with a worse prognosis, for example up to 30% of patients develop secondary pulmonary hypertension and thus right ventricle dysfunction. Increased right-ventricle systolic pressure is associated with increased mortality in patients with all forms of heart failure.
There is a lack of evidence about HFPEF. Drugs for treating systolic heart failure showed no improvement in mortality and prognosis. Diuretics are just able to relieve symptoms. There are no clinical trials concerning HFPEF with secondary pulmonary hypertension.
The endothelin system is not only activated in PAH, but also in pulmonary venous hypertension and congestive heart failure, where ET-1 levels rise with the severity of secondary pulmonary hypertension. Pulmonary congestion leads to endothelial dysfunction that results in increased levels of Endothelin-1 (ET-1).
ET-1 is a potent vasoconstrictor. In pulmonary arterial vessels the ETA receptor is the predominant receptor (ratio of ETA to ET B = 9:1), which is responsible for vasoconstriction and remodeling of the pulmonal vasculature. In heart failure the ETA receptor is upregulated. Elevated plasma ET-1 levels correlate with pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and inversely with peak exercise capacity.
Recent clinical and laboratory findings indicate comparable pathophysiological mechanisms in pulmonary hypertension secondary to left ventricular dysfunction and pulmonary arterial hypertension. Yet, despite an expanding application in pulmonary artery hypertension, according to current opinion, the oral dual endothelin (ETA/ETB) antagonist bosentan is not indicated for PVH caused by left ventricle / left atrial pressure overload and preserved systolic function. However, there are several studies which show some effects of pulmonary vessel dilating drugs in PAH and left ventricle dysfunction.
|Contact: Bernhard Koller, M.D.||+43 (0) 5223 email@example.com|
|Contact: Wilhelm Grander, M.D.||+43 (0) 5223 firstname.lastname@example.org|
|Hospital Mostviertel Waidhofen/Ybbs||Recruiting|
|Waidhofen, Lower Austria, Austria, 3340|
|Contact: Martin Gattermeier, Prim. M.D. 07442 9004 1810 email@example.com|
|Principal Investigator: Martin Gattermeier, Prim. M.D.|
|University Teaching Hospital Hall i.T.||Recruiting|
|Hall I. T., Tyrol, Austria, 6060|
|Contact: Wilhelm Grander, M.D. +43 (0) 5223 502 firstname.lastname@example.org|
|Contact: Bernhard Koller, M.D. +43 (0) 5223 502 email@example.com|
|Principal Investigator: Wilhelm Grander, M.D.|
|Sub-Investigator: Patrizia Eller, M.D.|
|Sub-Investigator: Johannes Schwaiger, M.D.|
|Sub-Investigator: Bernhard Koller, M.D.|
|University Teaching Hospital of the Elisabethinen, Linz||Recruiting|
|Linz, Upper Austria, Austria, 4010|
|Contact: Regina Steringer-Mascherbauer, M.D. 0732 7676 0 firstname.lastname@example.org|
|Principal Investigator: Regina Steringer-Mascherbauer, M.D.|
|Sub-Investigator: Christian Ebner, M.D.|
|Wels, Upper Austria, Austria, 4600|
|Contact: Thomas Weber, M.D. 07242 415 2215 email@example.com|
|Principal Investigator: Thomas Weber, Doz. M.D.|
|Sub-Investigator: Marcus Ammer, M.D.|
|Hohenems, Austria, 6845|
|Contact: Alexander Kopf, MD 0043 5576 703 firstname.lastname@example.org|
|Principal Investigator: Alexander Kopf, MD|
|Natters, Austria, 6161|
|Contact: Christan Geltner, MD 0043 512 5408 email@example.com|
|Principal Investigator: Christian Geltner, MD|
|University Hospital Salzburg||Recruiting|
|Salzburg, Austria, 5020|
|Contact: Jörg Eichinger, MD 0043 662 4482 firstname.lastname@example.org|
|Principal Investigator: Jörg Eichinger, MD|
|Principal Investigator:||Wilhelm Grander, M.D.||University Teaching Hospital Hall i.T.|