Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT01184404
Recruitment Status : Unknown
Verified December 2015 by Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was:  Recruiting
First Posted : August 19, 2010
Last Update Posted : December 22, 2015
Sponsor:
Information provided by (Responsible Party):
Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Tracking Information
First Submitted Date  ICMJE August 11, 2010
First Posted Date  ICMJE August 19, 2010
Last Update Posted Date December 22, 2015
Study Start Date  ICMJE September 2011
Estimated Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2010)
peak V'O2 [ Time Frame: 18 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01184404 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2010)
Right ventricular function [ Time Frame: 18 weeks ]
To determine 18 weeks after baseline differences in right ventricular function (assessed by transthoracic echocardiography)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bosentan Improves Clinical Outcome of Adults With Congenital Heart Disease or Mitral Valve Lesions Who Undergo CArdiac Surgery
Official Title  ICMJE Bosentan Improves Clinical Outcome of Adults With Congenital Heart Disease or Mitral Valve Lesions Who Undergo CArdiac Surgery
Brief Summary 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
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Congenital Heart Disease
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Bosentan
  • No Intervention: Control
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 18, 2010)
100
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01184404
Other Study ID Numbers  ICMJE 03603
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Sponsor  ICMJE Berto J Bouma
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Verification Date December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP