ClinicalTrials.gov
ClinicalTrials.gov Menu

Beta-blockers in i-PAH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01246037
Recruitment Status : Unknown
Verified January 2014 by A. Vonk Noordegraaf, VU University Medical Center.
Recruitment status was:  Active, not recruiting
First Posted : November 23, 2010
Last Update Posted : January 14, 2014
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
A. Vonk Noordegraaf, VU University Medical Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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 or disease Intervention/treatment Phase
Idiopathic Pulmonary Arterial Hypertension Drug: Bisoprolol Phase 1 Phase 2

  Show Detailed Description

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Beta-blocker Therapy in Idiopathic Pulmonary Arterial Hypertension
Study Start Date : February 2011
Actual Primary Completion Date : January 2014
Estimated Study Completion Date : April 2014

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Effectivity [ Time Frame: 6 months ]
    The primary efficacy endpoint is improvement in RV function as reflected by RVEF determined by means of cardiac MRI.

  2. Safety [ Time Frame: continue ]
    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 :
  1. Is Bisoprolol treatment effective in reducing sympathetic overdrive? [ Time Frame: 0,6,12 months ]
    Herefore the investigators use a C11-Hed-, H2O15- and a C11-acetate- nuclear scan

  2. 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 ]
    Pressure-Volume loops will be reconstructed from the combined right heart catheterization data and MRI measurements

  3. Is Bisoprolol treatment effective in improving the perfusion and mechanical efficiency (oxygen consumption per joule) of the heart? [ Time Frame: 0,6,12 months ]
    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.

  4. Is Bisoprolol effective in improving exercise capacity? [ Time Frame: Every two weeks ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: A. Vonk Noordegraaf, Prof. dr., VU University Medical Center
ClinicalTrials.gov Identifier: NCT01246037     History of Changes
Other Study ID Numbers: 2010-262
First Posted: November 23, 2010    Key Record Dates
Last Update Posted: January 14, 2014
Last Verified: January 2014

Keywords provided by A. Vonk Noordegraaf, VU University Medical Center:
Pulmonary Arterial Hypertension
Beta-blocker
Adrenergic Receptor Antagonist

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Adrenergic beta-Antagonists
Bisoprolol
Adrenergic Antagonists
 Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists