Betablocker Therapy in Pulmonary Arterial Hypertension

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-020424-21-NL
• Date of registration: 30/08/2010
• Prospective Registration: Yes
• Primary sponsor: VU medical center
• Public title: Betablocker Therapy in Pulmonary Arterial Hypertension
• Scientific title: Betablocker Therapy in Pulmonary Arterial Hypertension
• Date of first enrolment: 10/01/2011
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020424-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
Population:
The VUMC serves as a national tertiary referral centre for the diagnosis and treatment of PAH and had 1500 referrals in 10 years. Currently more than 100 idiopathic PAH patients are treated in the VUMC, which make it possible to select our study population with care from this large cohort.
We choose to limit our study to idiopathic PAH patients, since this is a well-characterized homogenous group with little or no co-morbidities. It is estimated that the current prevalence of iPAH in the Netherlands is about 200 patients. However, if our results turn out to be positive this might have an important impact on the management of other more common types of pulmonary hypertension.

Inclusion criteria
From our database containing currently 156 PAH patients we will carefully select patients who meet the following inclusion criteria:
• Idiopathic PAH patients
• Stable on PAH specific treatment defined
o No change in PAH specific treatment in the past 6 months
o No change in functional class in the past 6 months
o <10 % change in 6 minute walk distance in the past 6 months
• Functional class 2 or 3
• In sinus rhythm

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 are
• History of systemic hypertension, ischaemic heart disease, valvular disease or cardiomyopathy.
• Asthma
• Use of concomitant medication other than diuretics, Acenocoumarol and PAH targeted therapy
• History of cardiac arrhythmias or the use of anti-arrhythmic drugs
• Sick sinus syndrome
• systolic hypotension < 90 mmHg
• AV-block
• Clinically relevant sinus-bradycardia.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Idiopathic pulmonal arterial hypertension
MedDRA version: 12.1 Level: LLT Classification code 10020787 Term: Hypertension pulmonary

Intervention(s)

Product Name: Bisoprolol
Product Code: C07AB07
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Safety of Bisoprolol treatment in iPAH patients is not taken as a primary endpoint but seen as a precondition for this study and will be closely monitored. Dose titration will be guided by possible side effects. Furthermore, although beta-blocker are considered contraindicated in PAH patients, a considerable number of patients frequently receives beta-blocker therapy in an uncontrolled way (3), without any side effects being reported until now.
Our primary efficacy endpoint is improvement in RV function as reflected by RVEF determined by means of cardiac MRI.

Main Objective: The main question of this study is: ‘Is selective beta-blocker treatment safe and effective in reducing sympathetic overdrive, thereby improving RV function and remodeling in patients with iPAH?‘
Safety of Bisoprolol treatment in iPAH patients is not taken as a primary endpoint but seen as a precondition for this study and will be closely monitored. Dose titration will be guided by possible side effects. Furthermore, although beta-blocker are considered contraindicated in PAH patients, a considerable number of patients frequently receives beta-blocker therapy in an uncontrolled way (3), without any side effects being reported until now.
Our primary efficacy endpoint is improvement in RV function as reflected by RVEF determined by means of cardiac MRI.

Secondary Objective: In addition to the determination of RVEF, we will explore how beta-blocker therapy affects sympathetic overdrive, remodeling of the RV, single beat elastance, exercise capacity and mechanical efficiency. This will provide us with useful information with regards to the mode of action of beta-blocker therapy in iPAH, or alternatively, why beta-blocker may be ineffective in these patients. Therefore we have the following additional study questions:
* Is Bisoprolol treatment effective in reducing sympathetic overdrive?
* Is Bisoprolol effective in reversing maladaptive remodeling of the right ventricular wall, and does Bisoprolol thereby improve the diastolic properties of the right ventricle?
* Is Bisoprolol treatment effective in improving the perfusion and mechanical efficiency (oxygen consumption per joule) of the heart?
* Is Bisoprolol effective in improving exercise capacity?

Secondary ID(s)

bbbipah.1