Adding sotatercept to usual therapy for adults with Eisenmenger syndrome or unrepaired shunt-related pulmonary arterial hypertension

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

This study will test whether giving sotatercept in addition to standard PAH medicines helps adults with Eisenmenger syndrome or unrepaired shunt-associated pulmonary arterial hypertension that has not improved enough on vasodilators.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Kyushu University (Academic / other)
• Locations: 10 sites (Fukuoka, Not Required For This Country and 9 other locations)
• Trial ID: NCT07356778 on ClinicalTrials.gov

What this trial studies

This randomized phase 4 study enrolls about 36 adults in Japan whose pulmonary arterial hypertension from unrepaired atrial/ventricular septal defects or patent ductus arteriosus remains insufficiently controlled on vasodilator therapy. Participants are randomized 2:1 to receive sotatercept plus their usual vasodilator-based PAH care or to continue vasodilator-based care alone for 24 weeks. Sotatercept is given by injection every three weeks and all participants have clinic visits with tests at baseline, week 12, and week 24. The study is limited to ambulatory adults without very severe functional limitation (WHO class IV) or major comorbid organ disease.

Who should consider this trial

Good fit: Adults (≥18 years) with unrepaired ASD, VSD, or PDA and persistent PAH despite ≥90 days of vasodilator therapy, who meet hemodynamic or echocardiographic criteria and can walk ≥100 m on the 6-minute walk test, are ideal candidates.

Not a fit: Patients with very severe symptoms (WHO functional class IV), major renal/hepatic/lung disease, reduced left ventricular function, prior sotatercept use, or other unrepaired intracardiac shunts are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding sotatercept could improve exercise capacity, reduce PAH-related symptoms, and improve pulmonary vascular function or oxygenation for these patients.

How similar studies have performed: Earlier clinical trials of sotatercept in other forms of pulmonary arterial hypertension have reported promising improvements in hemodynamics and exercise capacity, supporting its use in related PAH populations.

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

Where this trial is running

Fukuoka, Not Required For This Country and 9 other locations

• Kyushu University Hospital — Fukuoka, Not Required For This Country, Japan (Recruiting)
• The Second Department of Internal Medicine, University of Occupational and Environmental Health — Fukuoka, Japan (Recruiting)
• Division of Cardiovascular Medicine, Kobe University Hospital — Kobe, Japan (Recruiting)
• Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine — Kyoto, Japan (Recruiting)
• Department of Cardiology, Nagoya University Hospital — Nagoya, Japan (Recruiting)
• Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University — Okayama, Japan (Recruiting)
• Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine — Sendai, Japan (Recruiting)
• Department of Cardiology, Keio University School of Medicine — Tokyo, Japan (Recruiting)
• Department of Cardiovascular Medicine, Kyorin University School of Medicine — Tokyo, Japan (Recruiting)
• Division of Cardiovascular Medicine, Department of Internal Medicine, Showa University Graduate School of Medicine — Tokyo, Japan (Recruiting)

Study contacts

• Study coordinator: Kazuya Hosokawa, MD, PhD

Conditions Eisenmenger Syndrome; Pulmonary Arterial Hypertension of Congenital Heart Disease; Eisenmenger syndrome; pulmonary arterial hypertension; Congential heart disease; sotatercept