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

NCT07356778 | Recruiting Phase 4

• 1 other identifier: CTR-2025-Sep
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension of Congenital Heart Disease; Eisenmenger Syndrome

Keywords

Eisenmenger syndrome; pulmonary arterial hypertension; Congential heart disease; sotatercept

Outcome Measures

Primary Outcomes (1)

• Change in 6-minute walk distance at 24 weeks from baseline

  24 weeks

Secondary Outcomes (5)

• 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

  24 weeks

• Change in NT-pro BNP at 24-week from baseline

  24 weeks

• Change in emPHasis-10 at 24-week from baseline

  24 weeks

Other Outcomes (9)

• PAH specific genetic test

  0 week

• Changes in blood pressure (systolic and diastolic)

  0, 12, 24 weeks

• Changes in pulse rate

  0, 12, 24 weeks

Study Arms (2)

Sotatercept add-on + vasodilator-based PAH therapy

EXPERIMENTAL

Drug: Sotatercept; Drug: vasodilator-based PAH therapy

vasodilator-based PAH therapy alone

ACTIVE COMPARATOR

Drug: vasodilator-based PAH therapy

Interventions

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.

Sotatercept add-on + vasodilator-based PAH therapy

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.

Sotatercept add-on + vasodilator-based PAH therapy; vasodilator-based PAH therapy alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kazuya Hosokawa: lead

Study Sites (10)

Kyushu University Hospital

Fukuoka, Not Required For This Country, 8150014, 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

Related Publications (1)

• 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.

  PMID: 41819579 DERIVED

MeSH Terms

Conditions

Eisenmenger Complex; Pulmonary Arterial Hypertension

Interventions

ACE-011

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor, Center for Advanced Medical Innovation, Kyushu University

Study Record Dates

• First Submitted: September 20, 2025
• First Posted: January 21, 2026
• Study Start: October 7, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (10)