Bosentan Improves Clinical Outcome of Adults With Congenital Heart Disease or Mitral Valve Lesions Who Undergo CArdiac Surgery (BOCA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01184404
First received: August 11, 2010
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

Cardiac surgery relieves symptoms and increases life expectancy in cardiac patients, with and without congenital heart disease (CHD). However, cardiac surgery involves many risks of complications, such as bleeding, arrhythmias, and death.Right ventricular failure is another complication, contributing to poor clinical outcome. Right ventricular failure is a clinical syndrome, often difficult to treat, characterized by edema, elevated jugular venous pressure, oliguria, hypotension, and in severe cases shock, multi organ failure and death. Patients with CHD and patients with mitral valve lesions are suspected to be at increased risk for developing right ventricular failure post-operatively. In addition, other clinical factors contributing to right ventricular failure are mechanical pulmonary ventilation, pulmonary hypertension and cardiac surgery. Right ventricular failure during cardiac surgery is caused by the cardiopulmonary bypass by reperfusion with high partial pressures of oxygen, air embolism, and the release of cytokines. The endothelin-1 cytokine induces vasoconstriction of the pulmonary arterioles resulting in right ventricular afterload elevation. Treating patients with an endothelin-1 receptor antagonist might improve clinical outcome post operatively by decreasing right ventricular afterload


Condition Intervention
Congenital Heart Disease
Drug: Bosentan

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bosentan Improves Clinical Outcome of Adults With Congenital Heart Disease or Mitral Valve Lesions Who Undergo CArdiac Surgery

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • peak V'O2 [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    The primary objective of this study is to determine changes in aerobic capacity (peak V'O2)in adult CHD patients or with mitral valve lesions who undergo surgery comparing treated with non-treated patients.


Secondary Outcome Measures:
  • Right ventricular function [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    To determine 18 weeks after baseline differences in right ventricular function (assessed by transthoracic echocardiography)


Estimated Enrollment: 100
Study Start Date: September 2011
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
The treatment group receives a starting dose of 62.5 mg tablet bosentan twice daily for four weeks followed by 125 mg tablet of bosentan twice daily two weeks prior to and 12 weeks after surgery.
Drug: Bosentan
The treatment group receives a starting dose of 62.5 mg tablet bosentan twice daily for four weeks followed by 125 mg tablet of bosentan twice daily two weeks prior to and 12 weeks after surgery.
Other Name: Tracleer Bosentan
No Intervention: Control

Detailed Description:

Rationale: Cardiac surgery relieves symptoms and increases life expectancy in cardiac patients, with and without congenital heart disease (CHD). However, cardiac surgery involves many risks of complications, such as bleeding, arrhythmias, and death. Right ventricular failure is another complication, contributing to poor clinical outcome. This clinical syndrome is often difficult to treat and is characterized by edema, elevated jugular venous pressure, oliguria, hypotension, and in severe cases shock, multi organ failure and death.

Patients at increased risk for developing post operative right ventricular failure are those with CHD or with mitral valve lesions, because of their elevated afterload. Other clinical factors contributing to right ventricular failure are mechanical pulmonary ventilation, pre-existing pulmonary hypertension and cardiac surgery. Right ventricular failure due to cardiac surgery is caused by the cardiopulmonary bypass, by reperfusion with high partial pressures of oxygen, air embolism, and the release of cytokines. The endothelin-1 cytokine release during cardiac surgery induces vasoconstriction of the pulmonary arterioles resulting in right ventricular afterload elevation. Therefore, we hypothesize that treating patients with an endothelin-1 receptor antagonist will improve clinical outcome, measured by aerobic capacity (peak V'O2), by decreasing right ventricular afterload peri-operatively.

Objective: To investigate whether an endothelin-1 receptor antagonist improves aerobic capacity (peak V'O2) in adults with CHD or with mitral valve lesions who undergo cardiac surgery.

Study design: A prospective randomized open label assessment with blinded end-points (PROBE-design). Total duration of the study is 18 weeks with 6 weeks pre-operative and 12 weeks post-operative treatment with bosentan.

Study population: Adults with CHD who undergo cardiac surgery and patients undergoing mitral valve surgery in the Academic Medical Centre in Amsterdam. Patients will be randomized six weeks before surgery. The study will continue until 12 weeks postoperatively.

Intervention: The treatment group receives a starting dose of 62.5 mg tablet bosentan twice daily for four weeks followed by 125 mg tablet of bosentan twice daily two weeks prior to and 12 weeks after surgery. The other group receives no study medication.

Main study parameters/endpoints: 1) on the intensive care unit a) hemodynamics b)Sequential Organ Failure Assessment (SOFA) score and c) hours of hospitalization 2) at discharge the right ventricular function (assessed by transthoracic echocardiography) 3) six weeks post-operatively a) clinical condition with exercise capacity (peak V'O2) b) right ventricular function (assessed by transthoracic echocardiography) c) the quality of life 4) twelve weeks post-operatively a) right ventricular function (assessed by transthoracic echocardiography) b) differences in clinical status and symptoms

  Eligibility

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

Inclusion Criteria:

  • Adults with CHD or mitral valve lesions who are scheduled for elective cardiac surgery

Exclusion Criteria:

  • Current treatment with bosentan
  • Systemic arterial pressure < 85 mmHg
  • Incapable of giving informed consent
  • Hypersensitivity to bosentan or any of its help substances
  • Moderate to severe liver disease: Child-Pugh class B or C
  • Raised plasma transaminases level > three times limiting value.
  • Simultaneous use of cyclosporine A
  • Percutaneous Transluminal Angioplasty procedures
  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: NCT01184404

Contacts
Contact: Mark Schuuring, MD 31205668687 m.j.schuuring@amc.uva.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, NH, Netherlands, 1105AZ
Contact: Mark Schuuring, MD    31205668687    m.j.schuuring@amc.uva.nl   
Principal Investigator: B J Bouma, MD PhD         
Sponsors and Collaborators
Berto J Bouma
  More Information

No publications provided

Responsible Party: Berto J Bouma, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01184404     History of Changes
Other Study ID Numbers: 03603
Study First Received: August 11, 2010
Last Updated: June 24, 2014
Health Authority: The Netherlands: EMEA European Medicines Agency

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Congenital heart disease
Cardiac surgery
Bosentan

Additional relevant MeSH terms:
Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014