BridgeMD
IMPACT-CTEPH
EU CTIS ID: 2024-513672-17-00
What this study is testing
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on pulmonary vascular resistance (PVR) prior to BPA in newly diagnosed and treatment-naïve subjects with inoperable CTEPH
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Signed informed consent
- Male or female ≥18 and ≤ 80 years of age at inclusion
- Newly diagnosed and treatment-naïve subjects with CTEPH judged as inoperable due to surgically inaccessible lesions but eligible for balloon pulmonary angioplasty, riociguat and macitentan by multidisciplinary team assessment and fulfilling the following criteria: a. Symptomatic pulmonary hypertension (PH) in WHO FC ≥ II. b. Confirmation of diagnosis based on 2 of the 3 following methods: i. Ventilation-perfusion lung scan ii. Digital subtraction pulmonary angiography (DSA) iii. CT pulmonary angiography (CTPA)
- Confirmation of inoperability based on CTPA scan and/or DSA
- Right-heart catheterization (RHC) in the 12-week period prior to screening visit or during screening period showing the following: a. Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg b. Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg or left ventricular end diastolic pressure ≤ 15 mmHg c. PVR at rest ≥ 400 dyn.sec.cm-5
- Subject anticoagulated (with either vitamin K antagonists or direct oral anticoagulants [e.g., factor IIa inhibitors, factor Xa inhibitors]), or treated with unfractionated heparin or low molecular weight heparin for at least 3 months prior to baseline RHC.
You likely can't join if
- Previous pulmonary endarterectomy
- History of life-threatening hemoptysis (>100 mL in 24 h) or subjects who have previously undergone bronchial arterial embolization for hemoptysis.
- Hemoglobin < 100 g/L.
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 × upper limit of the normal range.
- Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) > ULN; and/or Child-Pugh Class C.
- Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min/1.73 m²).
See the full eligibility criteria
Who can join
- Signed informed consent
- Male or female ≥18 and ≤ 80 years of age at inclusion
- Newly diagnosed and treatment-naïve subjects with CTEPH judged as inoperable due to surgically inaccessible lesions but eligible for balloon pulmonary angioplasty, riociguat and macitentan by multidisciplinary team assessment and fulfilling the following criteria: a. Symptomatic pulmonary hypertension (PH) in WHO FC ≥ II. b. Confirmation of diagnosis based on 2 of the 3 following methods: i. Ventilation-perfusion lung scan ii. Digital subtraction pulmonary angiography (DSA) iii. CT pulmonary angiography (CTPA)
- Confirmation of inoperability based on CTPA scan and/or DSA
- Right-heart catheterization (RHC) in the 12-week period prior to screening visit or during screening period showing the following: a. Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg b. Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg or left ventricular end diastolic pressure ≤ 15 mmHg c. PVR at rest ≥ 400 dyn.sec.cm-5
- Subject anticoagulated (with either vitamin K antagonists or direct oral anticoagulants [e.g., factor IIa inhibitors, factor Xa inhibitors]), or treated with unfractionated heparin or low molecular weight heparin for at least 3 months prior to baseline RHC.
- 6MWD ≥ 50m
- Women of childbearing potential must: a. Have a negative pre-treatment serum pregnancy test b. Agree to use reliable contraception from screening up to 1 month following discontinuation of the last study treatment.
What rules you out
- Previous pulmonary endarterectomy
- History of life-threatening hemoptysis (>100 mL in 24 h) or subjects who have previously undergone bronchial arterial embolization for hemoptysis.
- Hemoglobin < 100 g/L.
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 × upper limit of the normal range.
- Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 × upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) > ULN; and/or Child-Pugh Class C.
- Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min/1.73 m²).
- Systolic blood pressure <95mmHg.
- Treatment with strong cytochrome P450 3A4 (CYP3A4) inducers (e.g., rifabutin, rifampicin, carbamazepine, phenobarbital, phenytoin, St. John’s wort) ≤ 28 days prior to inclusion.
- Treatment with strong multi pathway P-glycoprotein (P-gp)/ breast cancer resistance protein (BCRP) inhibitors (e.g., lopinavir/ritonavir) ≤ 28 days prior to inclusion
- Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) or a moderate dual CYP3A4/CYP2C9 inhibitor (e.g., fluconazole, amiodarone) or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors ≤ 28 days prior to inclusion.
- Known hypersensitivity to riociguat or macitentan or to any excipient of their formulation.
- Previous balloon pulmonary angioplasty
- History of severe allergic-like reaction to intravascular administration of iodinated contrast media (including diffuse edema or facial edema with dyspnea, diffuse erythema with hypotension, laryngeal edema with stridor and/or hypoxia, bronchospasm, anaphylactic shock with hypotension and tachycardia).
- Subject who cannot remain in a supine position for at least 120 min for any reason.
- Pregnancy, breastfeeding, or intention to become pregnant during the study.
- Subjects with underlying medical disorders and anticipated life expectancy < 12 months (eg active cancer disease with localized and/or metastasized tumor mass).
- Alcohol abuse (at investigator discretion).
- Subject not covered by social security service.
- Any factor or condition likely to affect protocol compliance of the subject, as judged by the investigator.
- Any PAH-targeted therapy (e.g., any endothelin receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE-5i), soluble guanylate cyclase stimulator, prostacyclin, prostacyclin analog, or prostacyclin receptor agonist) at any time prior to inclusion.
- Ongoing or planned treatment with organic nitrates
- Known moderate-to-severe restrictive lung disease (i.e., total lung capacity < 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second [FEV1] < 60% of predicted, with FEV1 / forced vital capacity < 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
- Symptomatic coronary artery disease requiring nitrate use or intervention (e.g., Percutaneous Coronary Intervention, Coronary Artery Bypass Graft) anticipated in the 6-month period after inclusion.
- Acute myocardial infarction ≤ 12 weeks prior to inclusion.
- Left heart failure with an ejection fraction less than 40%.
- Cerebrovascular events (e.g., transient ischemic attack, stroke) ≤ 12 weeks prior to inclusion.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.