A Study of Sotatercept for Patients With Eisenmenger Syndrome or Unrepaired Shunt-Associated Pulmonary Arterial Hypertension Resistant to Vasodilator Therapy

Official title

An Open-label, Randomized, Controlled Trial to Evaluate the Efficacy of Sotatercept Add-on Therapy Compared to Standard PAH Therapy With Pulmonary Vasodilators for Pulmonary Arterial Hypertension Associated With Pulmonary Vasodilator-resistant, Unrepaired Congenital Shunts (ASD, VSD, PDA) Including Eisenmenger Syndrome：SuMILE Trial

Overview

What is this study about? This study will test whether adding sotatercept to usual medicines for pulmonary arterial hypertension (PAH) can help adults who have PAH due to unrepaired congenital heart defects (atrial or ventricular septal defect, or patent ductus arteriosus), including Eisenmenger syndrome. These conditions often cause long-standing changes in the lung blood vessels and low oxygen levels. Who can join? About 36 adults (age ≥18 years) in Japan whose PAH has not improved enough with pulmonary vasodilators may join. People with very severe symptoms (WHO class IV) or other serious illnesses will not be enrolled. What will happen if I join? Participants will be randomly assigned (like a coin flip, in a 2:1 ratio) to: Sotatercept + vasodilator-based PAH care, or vasodilator-based PAH care alone. The study lasts 24 weeks. Those who receive sotatercept will have injections every 3 weeks. All participants will have clinic visits and tests at the start, week 12, and week 24, including a 6-minute walk test (how far you can walk in 6 minutes), blood tests, questionnaires, and other heart-lung assessments used in routine PAH care. What are the possible benefits? Sotatercept improved exercise capacity and heart-lung measures in other PAH studies, but people with unrepaired heart defects were not included. This study may or may not help you directly, but it may help doctors learn how to use sotatercept safely in this group. What are the possible risks? Side effects seen with sotatercept include increase in haemoglobin, low platelets, nosebleeds, telangiectasia (small dilated blood vessels), bleeding, and blood clots. People with Eisenmenger syndrome can have both bleeding (for example, haemoptysis) and clotting risks. The study will check complete blood counts (CBC) regularly and adjust or pause dosing using label-based rules. Other risks are those of standard PAH care and blood tests. Time and location The study is conducted at multiple hospitals in Japan. Study participation lasts about 6 months. Costs and payments The study drug and study-specific tests will be provided at no cost. Usual medical care not required by the study will follow each hospital's standard billing. There is no required payment to join. Any travel reimbursement or stipends will follow site policy. Privacy Your information will be kept confidential. Results will be shared in journals and at meetings without using your name. Who to contact If you are interested or have questions, please contact the study team at the participating hospital.

Interventions

• Drug Sotatercept
  Sotatercept will be administered subcutaneously every 3 weeks for 24 weeks (total 8 injections): 0.3 mg/kg lead-in at Visit 1, then 0.7 mg/kg from Visit 2 if safety criteria are met. Dose holds/reductions follow label-concordant rules based on complete blood count (CBC) prior to each dose (e.g., hemoglobin rise \>4.0 g/dL from baseline; or \>2.0 g/dL from the previous dose and above ULN; or \>2.0 g/dL above ULN; and platelet count \<50,000/µL). Participants continue stable background PAH therapy
• Drug vasodilator-based PAH therapy
  Participants receive no sotatercept. They continue site-standard, stable PAH therapy for 24 weeks (endothelin receptor antagonist, PDE5 inhibitor/riociguat, and/or prostacyclin class as clinically indicated). Changes to background therapy are discouraged during the 24-week period unless required for safety; any changes are captured for analysis. The same visit schedule and assessments (e.g., 6-minute walk test, biomarkers, clinical events) apply as in the sotatercept arm.

Primary outcome measures

• Change in 6-minute walk distance at 24 weeks from baseline [Time frame: 24 weeks]

Secondary outcome measures (5)

• Mortality or lung transplantation [Time frame: 24 weeks]
• PH-related hospitalisation or initiation of parenteral prostacyclin [Time frame: 24 weeks]
• Change in WHO functional class at 24-week from baseline [Time frame: 24 weeks]
• Change in NT-pro BNP at 24-week from baseline [Time frame: 24 weeks]
• Change in emPHasis-10 at 24-week from baseline [Time frame: 24 weeks]

Eligibility criteria

Inclusion criteria

• adults (≥18 years)
• unrepaired ASD, VSD or PDA
• ≥90 days of pulmonary vasodilator therapy; and either (i) pulmonary vascular resistance (PVR) ≥5 Wood units and mean pulmonary arterial pressure (mPAP) > 20 mm Hg on right heart catheterization within 180 days, or (ii) echocardiographic tricuspid regurgitation velocity >3.4 m/s with right-to-left/bidirectional shunt plus resting SpO₂ ≤92% consistent with cyanosis
• baseline 6MWD ≥100 m
• ability to complete questionnaires

Exclusion criteria

• WHO functional class IV; other unrepaired intracardiac shunts
• severe renal/hepatic/parenchymal lung disease or LVEF <40%
• prior sotatercept use
• contraindication to sotatercept per label
• investigator-judged unsuitability

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 10 centers

• Kyushu University Hospital — Fukuoka
• The Second Department of Internal Medicine, University of Occupational and Environmental H — Fukuoka
• Division of Cardiovascular Medicine, Kobe University Hospital — Kobe
• Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectur — Kyoto
• Department of Cardiology, Nagoya University Hospital — Nagoya
• Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical S — Okayama
• Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine — Sendai
• Department of Cardiology, Keio University School of Medicine — Tokyo
• … and 2 more centers

Publications

• Yoshida K, Hosokawa K, Hiraide T, Akagi S, Ejiri K, Taniguchi Y, Adachi S, Inami T, Nakanishi N, Kataoka M, Satoh T, Tatebe S, Shinke T, Tomita H, Akazawa Y, Higaki T, Tagawa K, Ishikita A, Asakawa S, Abe K. Protocol for an open-label, randomised, controlled trial to evaluate the efficacy and safety of sotatercept add-on therapy compared with pulmonary vasodilator-based standard of care for pulmon PMID 41819579

Identifiers

NCT: NCT07356778 · CTR-2025-Sep

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗