Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome

This study has been completed.
Sponsor:
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00303004
First received: March 14, 2006
Last updated: January 23, 2008
Last verified: January 2008
  Purpose

The purpose of this study is to investigate if combination treatment with Bosentan and Sildenafil to patients with Eisenmenger syndrome is beneficial.


Condition Intervention Phase
Eisenmenger Syndrome
Drug: Bosentan and Sildenafil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • 6 minutes walking distance

Secondary Outcome Measures:
  • Pulmonary blood flow
  • Systemic blood flow
  • Pulmonary resistance
  • Shunt ratio
  • Erythropoitin
  • BNP
  • Saturation in rest
  • Saturation in activity
  • Quality of life
  • Right ventricle systolic and diastolic function
  • Working capacity
  • Oxygen consumption at rest
  • Oxygen consumption during maximal work

Estimated Enrollment: 20
Study Start Date: March 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Eisenmengers syndrome is condition with severe pulmonary arterial hypertension due to a shunting of blood from the left side of the heart to the right side of the heart. When the pressure in the pulmonary arteries levels the systemic blood pressure, blood begins to shunt from the right side of the heart to the left side of the heart leading to a condition with cyanosis, impaired physical capacity and increased mortality (Eisenmengers syndrome).

Several clinical trials have shown that there is a beneficial effect of treating patients with primary pulmonary arterial hypertension with Bosentan or Sildenafil and that a combination of these may have an additive or even synergistic effect. No clinical trials with Sildenafil and Bosentan has been conducted for patients with Eisenmengers syndrome. Observational studies and case stories indicate however that the effect of Bosentan or Sildenafil in patients with Eisenmengers syndrome may be as promising in these patients as in patients with primary pulmonary arterial hypertension.

We would like to examine the effect of treating patients with Eisenmengers Syndrome with a combination of Bosentan and Sildenafil.

The primary end point is change in physical performance measured with six minutes walking test.

Secondary end points is change in saturation, NYHA class, cardiac output (cardiac catheterization and innocor measurement), pulmonary vascular resistance (cardiac catheterization) shunt ratio (MRI), strain of right ventricle (BNP and echocardiography), quality of life and serum erythropoitin.

The trial is designed as a randomized, single centre, placebo controlled, double blind cross over study.

Twenty patients with Eisenmengers syndrome is included. All patients will be treated in three months with Bosentan. There after patients will be randomized to receive either Sildenafil (50 mg tid) or placebo as add on therapy for three month. Hereafter a cross over will be made and patients in combination treatment will receive only their native treatment and vice versa.

Examinations for primary and secondary endpoints will be made at baseline, before cross over and at the end of the study. All up titrating of medication will be performed during admittance. Patients will during the study period be close monitored with registration of adverse advents, physical examination and blood tests.

  Eligibility

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

Inclusion Criteria:

  • Eisenmenger syndrome
  • Negative pregnancy test

Exclusion Criteria:

  • Elevated liver enzymes to more than 3´times normal value
  • Hypotension (SBP < 90 mmhg).
  • Mandatory treatment with nitrates
  • Myocardial infarction within 3 months
  • Stroke within 3 months
  • Known allergy to Bosentan or Sildenafil
  • inherited degenerative diseases in retina
  • Breast feeding
  • Suspicion of risc of noncompliance.
  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: NCT00303004

Locations
Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Lars Soendergaard, MD Rigshospitalet, Denmark
  More Information

No publications provided by Rigshospitalet, Denmark

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kasper Iversen, Rigshospitaler
ClinicalTrials.gov Identifier: NCT00303004     History of Changes
Other Study ID Numbers: 01000
Study First Received: March 14, 2006
Last Updated: January 23, 2008
Health Authority: Denmark: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics

Additional relevant MeSH terms:
Eisenmenger Complex
Syndrome
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Disease
Heart Defects, Congenital
Heart Diseases
Pathologic Processes
Bosentan
Sildenafil
Antihypertensive Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on October 22, 2014