Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sotatercept add-on + vasodilator-based PAH therapy | Experimental |
| |
| vasodilator-based PAH therapy alone | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sotatercept | Drug | 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 (endothelin, nitric-oxide, prostacyclin pathways) per protocol; initiation or up-titration of PAH drugs during the 24-week treatment period is generally not permitted unless clinically mandated for safety and recorded as a protocol deviation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 6-minute walk distance at 24 weeks from baseline | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality or lung transplantation | 24 weeks | |
| PH-related hospitalisation or initiation of parenteral prostacyclin | 24 weeks | |
| Change in WHO functional class at 24-week from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| PAH specific genetic test | 0 week | |
| Changes in blood pressure (systolic and diastolic) | Office resting BP | 0, 12, 24 weeks |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kazuya Hosokawa, MD, PhD | Contact | +81-92-642-5360 | hosokawa.kazuya.712@m.kyushu-u.ac.jp | |
| Keimei Yoshida, MD, PhD | Contact | yoshida.keimei.713@m.kyushu-u.ac.jp |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kyushu University Hospital | Recruiting | Fukuoka | Not Required For This Country | 8150014 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41819579 | Derived | 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 pulmonary vasodilator-resistant pulmonary arterial hypertension associated with unrepaired congenital shunts (atrial septal defect, ventricular septal defect or patent ductus arteriosus), including Eisenmenger syndrome: the SuMILE trial. BMJ Open. 2026 Mar 12;16(3):e113430. doi: 10.1136/bmjopen-2025-113430. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| vasodilator-based PAH therapy | Drug | 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. |
|
A higher score indicates more severe symptom |
| 24 weeks |
| Change in NT-pro BNP at 24-week from baseline | 24 weeks |
| Change in emPHasis-10 at 24-week from baseline | A higher score indicates more severe symptom | 24 weeks |
| Changes in pulse rate |
bpm |
| 0, 12, 24 weeks |
| Changes in oxygen saturation | Pulse Oxygen Saturation (Office, Resting) | 0, 12, 24 weeks |
| Changes in hemoglobin | g per dL | 0, 12, 24 weeks |
| Changes in platlet counts | 0, 12, 24 weeks |
| Changes in catheter-based mPAP | mm Hg | 0, 24 weeks |
| Changes in catheter-based PVR | Wood units | 0, 24 weeks |
| Changes in catheter-based Qp/Qs | 0, 24 weeks |
| The Second Department of Internal Medicine, University of Occupational and Environmental Health | Recruiting | Fukuoka | Japan |
|
| Division of Cardiovascular Medicine, Kobe University Hospital | Recruiting | Kobe | Japan |
|
| Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine | Recruiting | Kyoto | Japan |
|
| Department of Cardiology, Nagoya University Hospital | Recruiting | Nagoya | Japan |
|
| Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University | Recruiting | Okayama | Japan |
|
| Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine | Recruiting | Sendai | Japan |
|
| Department of Cardiology, Keio University School of Medicine | Recruiting | Tokyo | Japan |
|
| Department of Cardiovascular Medicine, Kyorin University School of Medicine | Recruiting | Tokyo | Japan |
|
| Division of Cardiovascular Medicine, Department of Internal Medicine, Showa University Graduate School of Medicine | Recruiting | Tokyo | Japan |
|
| ID | Term |
|---|---|
| D004541 | Eisenmenger Complex |
| D000081029 | Pulmonary Arterial Hypertension |
| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006976 | Hypertension, Pulmonary |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C542017 | ACE-011 |
Not provided
Not provided
Not provided