Sota-ES - Sotatercept in Patients With Congenital Heart Disease and Eisenmenger´s Syndrome

Inclusion criteria

• Age ≥18 years
• Congenital heart disease with Eisenmenger syndrome (known unrepaired atrial septal defect, and/or ventricular septal defect, and/or patent ductus arteriosus; patients with anomalous pulmonary venous drainage will not be considered)
• Eisenmenger syndrome defined as right-to-left or bi-directional shunt with a mPAP >25 mmHg, PAWP < 15 mmHg, and PVR >5 WU
• In patients with pre-tricuspid shunt, the consideration of Eisenmenger syndrome requires one of the following: Systemic arterial O2 saturation (SaO2) at rest <88% and more than 70%, and/or SaO2 <80% during 6MWT, and secondary erythrocytosis (Hb > 15.0 g/dl for females and 16.0 g/dl for males)
• On stable doses of background PAH therapy* and diuretics (i.e., patient-individual dose goal for each therapy achieved) for ≥30 days
• 6-minute walking distance >100 m
• WHO-FC II or III
• Written informed consent

Exclusion criteria

• Age <18 years

• Diagnosis of pulmonary hypertension groups 2, 3, 4, or 5
• Hospitalization or change in PAH background therapies within 30 days prior to screening (changes in dose of diuretics or parenteral prostanoids [<10% change in infusion rate over the preceding 3 months] are allowed)
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mmHg or sitting diastolic blood pressure >100 mmHg during screening visit after a period of rest
• Baseline systolic blood pressure <90 mmHg at screening
• Left ventricular systolic dysfunction (LVEF 40%)
• Restrictive lung disease with a TLC < 60% AND demonstration of more than mild fibrosis on chest CT prior to enrolment (note that patients with congenital heart disease may have thoracic cage deformities [e.g. pectus] that may lead to thoracic cage restriction in the absence of parenchymal lung disease).
• Obstructive lung disease (FEV1 < 60% pred. and FEV1/FVC <60%)
• Chronic thromboembolic disease (intermediate or high probability) on V/Q scan and evidence of distal thromboembolism on CT angiography (note that proximal in-situ thrombosis is a known complication of Eisenmenger's and will not be considered an exclusion criterion - such patients may be reviewed centrally for inclusion)
• Significant liver disease (Child II or III)
• Any of the following clinical laboratory values at the screening visit:

• Estimated glomerular filtration rate (eGFR) <30 mL/min/m2 (as defined by the Modification of Diet in Renal Disease [MDRD] equation)
• Serum alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels >3 × ULN (bilirubin criterion waived if there is a documented history of Gilbert's syndrome)
• Baseline platelet count <50,000/µl (<50.0 x 109/L) at screening
• Documented episodes of previous repetitive hyperviscosity syndrome
• History of haemoptysis within 12 months prior to screening, and/or repeated severe epistaxis (≥ 1 episode per month)
• Uncorrected iron deficiency (iron stores must be normal defined as a Ferritin > 100 and transferrin saturation [TSAT] ≥ 20%)
• Recent (< 3 months) enrolment into a rehabilitation program
• Untreated sleep disordered breathing with an AHI > 10. Patients with sleep apnea will need to have been on CPAP or BiPAP for 3 months prior to enrolment.
• Prior or current exposure to sotatercept or luspatercept
• Treatment by phlebotomy within 1 month prior to screening
• Participation in another interventional study
• Pregnant (serum B-HCG) or lactating women