Eisenmenger SyndromePhase 4SuMILENCT07356778
A Study of Sotatercept for Patients With Eisenmenger Syndrome or Unrepaired Shunt-Associated Pulmonary Arterial Hypertension Resistant to Vasodilator Therapy
A Phase 4 study testing Sotatercept and vasodilator-based PAH therapy in people with Eisenmenger Syndrome and Pulmonary Arterial Hypertension of Congenital Heart Disease, run by Kazuya Hosokawa at 10 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Eisenmenger Syndrome, Pulmonary Arterial Hypertension of Congenital Heart Disease
- What is being tested?
- Sotatercept and vasodilator-based PAH therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 10 sitesJapan
- Study dates
- 7 Oct 2025to 30 Apr 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Keimei Yoshida, MD, PhD contact
10 sites in 1 country
Japan10 sites, 10 recruiting
- Recruiting
Kyushu University Hospital
Fukuoka, Not Required For This Country, 8150014
Kazuya Hosokawa, +81-92-642-1151, hosokawa.kazuya.712@m.kyushu-u.ac.jp
Ayako Ishikita
- Recruiting
The Second Department of Internal Medicine, University of Occupational and Environmental Health
Fukuoka
Masaharu Kataoka, +81--603-1611, mkataoka@med.uoeh-u.ac.jp
Masaharu Kataoka
- Recruiting
Division of Cardiovascular Medicine, Kobe University Hospital
Kobe
Yu Taniguchi, +81-78-382-5111, yu.taniguchi007@gmail.com
Yu Taniguchi
- Recruiting
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Kyoto
Naohiko Nakanishi, +81-75-703-5101, naka-nao@koto.kpu-m.ac.jp
Naohiko Nakanishi
- Recruiting
Department of Cardiology, Nagoya University Hospital
Nagoya
Shiro Adachi, +81-52-741-2111, adachi.shiro.b6@f.mail.nagoya-u.ac.jp
Shiro Adachi
- Recruiting
Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Okayama
Satoshi Akagi, +81-86-223-7151, akagi-s@cc.okayama-u.ac.jp
Satoshi Akagi
- Recruiting
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
Sendai
Taijyu Sato, +81-22-717-7000, s-taiju@cardio.med.tohoku.ac.jp
Taijyu Sato
- Recruiting
Department of Cardiology, Keio University School of Medicine
Tokyo
Takahiro Hiraide, +81-3-3353-1211, t.hiraide.a6@keio.jp
Takahiro Hiraide
- Recruiting
Department of Cardiovascular Medicine, Kyorin University School of Medicine
Tokyo
Takumi Inami, +81-22-47-5511, tinami@ks.kyorin-u.ac.jp
Takumi Inami
- Recruiting
Division of Cardiovascular Medicine, Department of Internal Medicine, Showa University Graduate School of Medicine
Tokyo
Toshiro Shinke, shinke@med.showa-u.ac.jp
Toshiro Shinke
About this study
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
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.
Read more
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.
- Being tested
- Sotatercept, vasodilator-based PAH therapy
- Keywords
- Eisenmenger syndrome, pulmonary arterial hypertension, Congential heart disease, sotatercept
- Medical subject headings
- Eisenmenger Complex, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotaterceptDrug
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.
vasodilator-based PAH therapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Sotatercept add-on + vasodilator-based PAH therapy | Experimental | Not described Receives: Drug: Sotatercept; Drug: vasodilator-based PAH therapy |
| vasodilator-based PAH therapy alone | Active comparator | Not described Receives: Drug: vasodilator-based PAH therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 6-minute walk distance at 24 weeks from baseline
Measured: 24 weeks
Secondary outcomes (5)
Mortality or lung transplantation
Measured: 24 weeks
PH-related hospitalisation or initiation of parenteral prostacyclin
Measured: 24 weeks
Change in WHO functional class at 24-week from baseline
A higher score indicates more severe symptom
Measured: 24 weeks
Change in NT-pro BNP at 24-week from baseline
Measured: 24 weeks
Change in emPHasis-10 at 24-week from baseline
A higher score indicates more severe symptom
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2026
- Study start7 Oct 2025
- Primary completion31 Aug 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Eisenmenger SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kazuya Hosokawa
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kazuya Hosokawa, Kyushu University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07356778
- Sponsor's protocol ID
- CTR-2025-Sep
- Acronym
- SuMILE
- Status last verified
- Jan 2026
- First submitted
- 20 Sep 2025
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 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.
PubMed 41819579
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07356778
- Acronym / sponsor ID
- SuMILE / CTR-2025-Sep
- Keywords
- Eisenmenger syndrome, pulmonary arterial hypertension, Congential heart disease, sotatercept
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Kazuya HosokawaUniversity, hospital or other
- Study start
- 7 Oct 2025 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 21 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SotaterceptSotatercept 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. | Drug | Sotatercept add-on + vasodilator-based PAH therapy |
| vasodilator-based PAH therapyParticipants 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. | Drug | Sotatercept add-on + vasodilator-based PAH therapy, vasodilator-based PAH therapy alone |
Primary outcome
Change in 6-minute walk distance at 24 weeks from baseline
Time frame: 24 weeks
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2026.
- Derived from this study: PubMed 41819579Yoshida 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.
- Individual participant dataSharing planned: No
Related trials for Eisenmenger Syndrome
Not yet recruitingPhase 2
Sota-ES - Sotatercept in Patients With Congenital Heart Disease and Eisenmenger´s Syndrome
Congenital Heart Disease (CHD), Eisenmenger Syndrome
RecruitingObservational study
COMPERA / COMPERA-KIDS
Pulmonary Arterial Hypertension (PAH), Pulmonary Hypertension (PH)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Keimei Yoshida, MD, PhD contact
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sotatercept and vasodilator-based PAH therapy in people with Eisenmenger Syndrome and Pulmonary Arterial Hypertension of Congenital Heart Disease, run by Kazuya Hosokawa at 10 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kazuya Hosokawa, MD, PhD (+81-92-642-5360, hosokawa.kazuya.712@m.kyushu-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in 6-minute walk distance at 24 weeks from baseline (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07356778, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.