Beta-blockers in i-PAH - Full Text View

Purpose

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?'.

In addition to the determination of RVEF, the investigators will explore how beta-blocker therapy affects sympathetic overdrive, remodeling of the RV, single beat elastance, exercise capacity and mechanical efficiency.

30 iPAH patients will be randomized to either Bisoprolol- or placebo-treatment in a double-blinded fashion. A cross-over trial design will be used to increase the power of the study and to assess long-term effects of Bisoprolol-treatment and -withdrawal. The medication will be given in an escalating dose regimen (as described in the 'farmacotherapeutisch kompas', www.fk.cvz.nl) and treatment will be monitored along the guidelines of the American Heart Association.

Condition	Intervention	Phase
Idiopathic Pulmonary Arterial Hypertension	Drug: Bisoprolol	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Beta-blocker Therapy in Idiopathic Pulmonary Arterial Hypertension

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Bisoprolol Bisoprolol hydrochloride Bisoprolol fumarate Adrenergic beta-Antagonists

Genetic and Rare Diseases Information Center resources: Pulmonary Arterial Hypertension

U.S. FDA Resources

Further study details as provided by VU University Medical Center:

Primary Outcome Measures:

Effectivity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The primary efficacy endpoint is improvement in RV function as reflected by RVEF determined by means of cardiac MRI.
Safety [ Time Frame: continue ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Is Bisoprolol treatment effective in reducing sympathetic overdrive? [ Time Frame: 0,6,12 months ] [ Designated as safety issue: No ]
Herefore the investigators use a C11-Hed-, H2O15- and a C11-acetate- nuclear scan
Is Bisoprolol effective in reversing maladaptive remodeling of the right ventricular wall, and does Bisoprolol thereby improve the diastolic properties of the right ventricle? [ Time Frame: 0,6 and 12 months ] [ Designated as safety issue: No ]
Pressure-Volume loops will be reconstructed from the combined right heart catheterization data and MRI measurements
Is Bisoprolol treatment effective in improving the perfusion and mechanical efficiency (oxygen consumption per joule) of the heart? [ Time Frame: 0,6,12 months ] [ Designated as safety issue: No ]
Perfusion will be measured by using the H2O tracer. Oxygen consumption of the right ventricle will be estimated from the uptake of the acetate tracer. Right ventricular power output will be derived from the right heart catheterization data.
Is Bisoprolol effective in improving exercise capacity? [ Time Frame: Every two weeks ] [ Designated as safety issue: No ]
This will be measured by means of the maximal oxygen uptake which is measured by means of the incremental cardiopulmonary exercise test and six minute walking distance.


Estimated Enrollment:	30
Study Start Date:	February 2011
Estimated Study Completion Date:	April 2014
Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: First placebo First half year placebo, second half year bisoprolol	Drug: Bisoprolol In the first 4 months of study, the dose of the drug will be gradually increased; the titration scheme is based on the 'farmacotherapeutisch kompas' and monitored according to the ACC/AHA/ESC guidelines. Up titration will be performed under the responsibilities of an experienced heart failure cardiologist and pulmonologist.
Experimental: First Bisoprolol First half year bisoprolol, second half year placebo	Drug: Bisoprolol In the first 4 months of study, the dose of the drug will be gradually increased; the titration scheme is based on the 'farmacotherapeutisch kompas' and monitored according to the ACC/AHA/ESC guidelines. Up titration will be performed under the responsibilities of an experienced heart failure cardiologist and pulmonologist.

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Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Idiopathic PAH patients
Stable on PAH specific treatment defined
- No change in PAH specific treatment in the past 6 months
- No change in functional class in the past 6 months
- <10 % change in 6 minute walk distance in the past 6 months
Functional class 2 or 3
In sinus rhythm

Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01246037

Locations


Netherlands
VUmc
Amsterdam, Netherlands

Sponsors and Collaborators

VU University Medical Center

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators


Principal Investigator:	Anton Vonk Noordegraaf, Prof. MD PhD	VU University Medical Center, pulmonary department

More Information

No publications provided


Responsible Party:	A. Vonk Noordegraaf, Prof. dr., VU University Medical Center
ClinicalTrials.gov Identifier:	NCT01246037 History of Changes
Other Study ID Numbers:	2010-262
Study First Received:	November 18, 2010
Last Updated:	January 13, 2014
Health Authority:	Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by VU University Medical Center:


Pulmonary Arterial Hypertension Beta-blocker Adrenergic Receptor Antagonist

Additional relevant MeSH terms:


Hypertension Cardiovascular Diseases Vascular Diseases Adrenergic beta-Antagonists Bisoprolol Adrenergic Agents Adrenergic Antagonists Adrenergic beta-1 Receptor Antagonists Antihypertensive Agents	Autonomic Agents Cardiovascular Agents Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Sympatholytics Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015