Clinical trial NCT00303004: Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome
Official title: Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eisenmenger Syndrome
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2006-03-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: 6 minutes walking distance
Secondary outcomes:
measure: Pulmonary blood flow
measure: Systemic blood flow
measure: Pulmonary resistance
measure: Shunt ratio
measure: Erythropoitin
measure: BNP
measure: Saturation in rest
measure: Saturation in activity
measure: Quality of life
measure: Right ventricle systolic and diastolic function
measure: Working capacity
measure: Oxygen consumption at rest
measure: Oxygen consumption during maximal work
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Lars Soendergaard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iversen K, Jensen AS, Jensen TV, Vejlstrup NG, Sondergaard L. Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial. Eur Heart J. 2010 May;31(9):1124-31. doi: 10.1093/eurheartj/ehq011. Epub 2010 Mar 3.