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

Congenital Heart Disease Clinical Trial

— BOCA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01184404
• Other study ID #: 03603
• Status: Recruiting
• Phase: N/A
• First received: August 11, 2010
• Last updated: December 21, 2015
• Start date: September 2011

Study information

• Verified date: December 2015
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Mark Schuuring, MD
• Phone: 31205668687
• Email: m.j.schuuring[@]amc.uva.nl
• Is FDA regulated: No
• Health authority: The Netherlands: EMEA European Medicines Agency
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam	NH

Sponsors (1)

Lead Sponsor	Collaborator
Berto J Bouma

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	peak V'O2	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.	18 weeks	No
Secondary	Right ventricular function	To determine 18 weeks after baseline differences in right ventricular function (assessed by transthoracic echocardiography)	18 weeks	No