SIRIUS - Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg, Sotatercept.
- Who it may be relevant to
- Registry conditions: Pulmonary Arterial Hypertension (PAH). Basic parameters: 18 years — 70 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
SIRIUS - A Prospective, Non-randomized, Open-label, Proof-of-concept Study of Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension A Single-arm, Multi-center, Interventional Phase II Study
Overview
The study aims to see how 24 weeks of triple therapy-an endothelin receptor antagonist (ERA), a phosphodiesterase-5 inhibitor (PDE5i), and sotatercept-affects pulmonary vascular resistance (PVR) in patients with newly diagnosed pulmonary arterial hypertension (PAH). SIRIUS is a 24-week, single-arm, open-label study with up to 42 days of screening and a 28-day safety follow-up. It will enroll 25 patients and will be conducted only in countries where all treatments are available and covered. After 24 weeks, PAH treatment is decided by the doctor.
Interventions
- Drug Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg
subcutaneously administration in 3-weekly intervals - Drug Sotatercept
Patients are traitment-naiive before start of study. Therapy will be a triple combination therapy with an endothelin receptor antagonist (ERA), a phosphodiesterase-5 inhibitor (PDE5i), and Sotatercept
Primary outcome measures
- Assessment of the effect on pulmonary vascular resistance (PVR) [Time frame: 24 weeks]
Eligibility criteria
Inclusion criteria
- Age 18- 70 years
- Treatment-naïve patients diagnosed within 12 weeks prior to screening with I/H/D-PAH or PAH associated with corrected congenital heart disease (disease (≥12 months after correction). Patients who have received treatment with PDE5is and/or ERAs for up to 6 weeks after diagnosis are eligible provided that state-of-the-art right heart catheterization has been performed at PAH diagnosis.
- PVR >5 WU, mPAP ≥35 mmHg and PAWP or LVEDP ≤15 mmHg at PAH diagnosis.
- Signed written informed consent
- Normal blood counts for platelets and erythrocytes
- Women of childbearing potential must be willing to remain abstinent or use adequate and reliable contraception throughout the study and for at least 4 months after the last dose of study medication has been received.
- WOCBP must use one of the following highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly - according to recommendations by the European Heads of Medicines Agencies - from at least 14 days before the first administration of study medication until 4 month after the last administration of study medication:
- combined (estrogen and progestogen containing) hor-monal contraception associated with inhibition of ovulation:
- oral
- intravaginal
- transdermal
- progestogen-only hormonal contraception associatedwith inhibition of ovulation:
- oral
- injectable
- implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomized partner
- sexual abstinence
- Male participants with female partner(s) of childbearing potential are eligible to participate in the study if they agree to the following during treatment and until 304 daysmonths after the last administration of study medication:
- Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator.
- Male participants are required to use a condom during treatment and until 30 days4 months after the last administration of study medication.
- Female partners of male participants who have not undergone a vasectomy with the absence of sperm confirmed or a bilateral orchiectomy should consider use of effective methods of contraception during treatment and until 30 days4 months after the last administration of study medication.
- Sperm donation is not allowed during treatment and until 4 months after the last administration of study medication.
Exclusion criteria
- Other Forms of PH or PAH
- Use of PAH medications for more than 6 weeks prior to screening
- Symptoms or signs of clinically relevant lung disease, including TLC < 70%, FEV1/FVC <60%, and DLCO <45%, respectively
- Signs of left heart failure with reduced or preserved ejection fraction, including LVEF <50%, LAVI >34 ml/m2, E/é ≥15, or permanent atrial fibrillation, respectively.
- History of severe bleeding/haemorrhage
- Therapy with prostacyclin and/or antithrombotic agents
- eGFR <30 ml/min/m2.
- Pregnancy or breastfeeding
- Hypersensitivity to the active substance or to any of the excipients
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07266519 · KKS-322 · 2025-522266-67-00