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Beta-blockers in i-PAH

This study is currently recruiting participants.
Verified February 2013 by VU University Medical Center
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
A. Vonk Noordegraaf, VU University Medical Center
ClinicalTrials.gov Identifier:
NCT01246037
First received: November 18, 2010
Last updated: February 4, 2013
Last verified: February 2013
History of Changes
  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:

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
Estimated Primary Completion Date: February 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01246037

Contacts
Contact: Jasmijn SJ van Campen, MD +31-20-4444710 ext 7438 j.vancampen@vumc.nl
Contact: Karin de Boer, MD +31-204444444 k.deboer@vumc.nl

Locations
Netherlands
VUmc Recruiting
Amsterdam, Netherlands
Contact: Jasmijn SJ van Campen, MD     +31 20 444 2187     j.vancampen@vumc.nl    
Contact: Karin de Boer, MD     +31 20 4445040     k.deboer@vumc.nl    
Principal Investigator: Anton Vonk Noordegraaf, Prof MD PhD            
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: February 4, 2013
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, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Adrenergic beta-Antagonists
Bisoprolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists

ClinicalTrials.gov processed this record on May 16, 2013