Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome
Combination Treatment With Bosentan and Sildenafil to Patients With Eisenmengers Syndrome
The purpose of this study is to investigate if combination treatment with Bosentan and
 Sildenafil to patients with Eisenmenger syndrome is beneficial.
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.
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.