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

Kazuya Hosokawa

Status and phase: Enrolling; Phase 4

Conditions: Pulmonary Arterial Hypertension of Congenital Heart Disease; Eisenmenger Syndrome

Treatments: Drug: Sotatercept; Drug: vasodilator-based PAH therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07356778

CTR-2025-Sep

Details and patient eligibility

About

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.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 2 patient groups

Sotatercept add-on + vasodilator-based PAH therapy

Experimental group

Treatment:

Drug: vasodilator-based PAH therapy

Drug: Sotatercept

vasodilator-based PAH therapy alone

Active Comparator group

Treatment:

Drug: vasodilator-based PAH therapy