Beta-blockers in i-PAH

NCT01246037 | Unknown Phase 1 DMC

• 1 other identifier: 2010-262
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; Beta-blocker; Adrenergic Receptor Antagonist

Outcome Measures

Primary Outcomes (2)

• Effectivity

  The primary efficacy endpoint is improvement in RV function as reflected by RVEF determined by means of cardiac MRI.

  6 months

• Safety

  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.

  continue

Secondary Outcomes (4)

• Is Bisoprolol treatment effective in reducing sympathetic overdrive?

  0,6,12 months

• Is Bisoprolol effective in reversing maladaptive remodeling of the right ventricular wall, and does Bisoprolol thereby improve the diastolic properties of the right ventricle?

  0,6 and 12 months

• Is Bisoprolol treatment effective in improving the perfusion and mechanical efficiency (oxygen consumption per joule) of the heart?

  0,6,12 months

• Is Bisoprolol effective in improving exercise capacity?

  Every two weeks

Study Arms (2)

First placebo

EXPERIMENTAL

First half year placebo, second half year bisoprolol

Drug: Bisoprolol

First Bisoprolol

EXPERIMENTAL

First half year bisoprolol, second half year placebo

Drug: Bisoprolol

Interventions

Bisoprolol DRUG

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.

First Bisoprolol; First placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

VUmc

Amsterdam, Netherlands

Location

Related Publications (1)

• van Campen JS, de Boer K, van de Veerdonk MC, van der Bruggen CE, Allaart CP, Raijmakers PG, Heymans MW, Marcus JT, Harms HJ, Handoko ML, de Man FS, Vonk Noordegraaf A, Bogaard HJ. Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study. Eur Respir J. 2016 Sep;48(3):787-96. doi: 10.1183/13993003.00090-2016. Epub 2016 Jul 7.

  PMID: 27390285 DERIVED

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension; Pulmonary Arterial Hypertension

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Anton Vonk Noordegraaf, Prof. MD PhD

  VU University Medical Center, pulmonary department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: November 18, 2010
• First Posted: November 23, 2010
• Study Start: February 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: April 1, 2014
• Last Updated: January 14, 2014

Record last verified: 2014-01

Locations

NL (1)