Thromboembolic Pulmonary HypertensionPhase 2/3IMPACT-CTEPHNCT04780932
Initial Dual Oral Combination Therapy Versus Standard-of-care Initial Oral Monotherapy Prior to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension
A Phase 2/3 study testing Macitentan 10mg in people with Thromboembolic Pulmonary Hypertension and Chronic Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by an obstruction of proximal or more distal pulmonary arteries by residual organized thrombi, combined with a variable microscopic pulmonary vasculopathy (microvasculopathy). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Thromboembolic Pulmonary Hypertension, Chronic Disease, Inoperable Disease
- What is being tested?
- Macitentan 10mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteFrance
- Study dates
- 14 Jun 2021to 3 Jul 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to 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:
- Symptomatic pulmonary hypertension (PH) in WHO FC ≥ II.
- Confirmation of diagnosis based on 2 of the 3 following methods:
- Ventilation-perfusion lung scan ii. Digital subtraction pulmonary angiography (DSA) iii. CT pulmonary angiography (CTPA).
Show all 16Show fewer
- 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:
- Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg
- Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg or left ventricular end diastolic pressure ≤ 15 mmHg
- 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:
- Have a negative pre-treatment serum pregnancy test
- Agree to use reliable contraception from screening up to 1 month following discontinuation of the last study treatment.
Who cannot join
- Previous pulmonary endarterectomy.
- Previous balloon pulmonary angioplasty.
- 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.
Show all 26Show fewer
- 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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Initial Dual Oral coMbination Therapy Versus Standard-of-care Initial Oral Monotherapy Prior to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary hyperTension
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by an obstruction of proximal or more distal pulmonary arteries by residual organized thrombi, combined with a variable microscopic pulmonary vasculopathy (microvasculopathy). Besides lifelong anticoagulation, surgical pulmonary endarterectomy is the treatment of choice in subjects with proximal CTEPH affecting large pulmonary arteries. However, around half of CTEPH subjects are not operated, mainly because of distal lesions inaccessible to surgery. International data have reported survival rates of 88, 79, and 70% at 1, 2, and 3 years, respectively, in subjects with inoperable CTEPH, underscoring the need for better treatment strategies. In those subjects, current guidelines recommend medical therapy with or without balloon pulmonary angioplasty (BPA). Currently, only one drug (riociguat), targeting the NO pathway, is approved and reimbursed in Europe. Thus, riociguat monotherapy is considered as the standard-of-care treatment for subjects newly diagnosed with inoperable CTEPH. Recently, macitentan, targeting the endothelin-1 pathway, showed to be also effective in subjects with inoperable CTEPH. However, macitentan is currently not approved for CTEPH in Europe.
BPA has been also reported to improve hemodynamics, symptoms and exercise capacity. However, complications, including mainly vascular injury, may occur during this procedure and it has been shown that the risk of BPA-related complications was strongly related to the level of pre-BPA mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). Medical therapy and BPA have in fact complementary effects since they target different lesions. Indeed, BPA targets fibrotic organized thrombi in the segmental arteries down to small pulmonary arteries of 2-5 mm in diameter. Medical therapy, for its part, targets microvasculopathy, similar to that observed in pulmonary arterial hypertension (PAH), in vessels less than 0.5 mm in diameter. Therefore, it is strongly believed that the use of medical therapy prior to BPA may reduce the risk of BPA-related complications by improving pulmonary hemodynamics and may improve global efficacy. In PAH, initial dual oral combination therapy with drugs targeting the NO and endothelin pathways is considered as a standard of care, more efficacious than monotherapy and safe. In contrast, there are no data from controlled trials regarding the efficacy and safety of initial combination therapy regimens versus standard-of-care monotherapy in treatment-naïve subjects with inoperable CTEPH.
The investigators hypothesize that initial dual oral combination therapy may be superior to standard-of-care riociguat monotherapy for improving pulmonary hemodynamics prior to BPA and for reducing the risk of BPA-related complications.
Read the detailed description
The Screening period will last up 28 days maximum. It begins at the first screening assessment and ends with subject inclusion. The Screening visit date is the date when the first screening assessment is performed.
The Treatment period will start at Day 1 with the first dose of riociguat and ends at Week 42 / End-of-Treatment (EOT) visit.
On Day 8, the experimental treatment with macitentan / placebo will be started.
During this period, regular hospital visits will be performed (Week 16, Week 29).
In addition, laboratory tests will be performed every 4 weeks as part of standard of care.
Subjects who are still symptomatic (WHO FC II to IV) and have PVR≥ 240 dyn.sec.cm-5 at week 16 will be offered additional treatment by BPA.
Safety follow-up period: After study drug discontinuation, all subjects will enter a Safety follow-up period which ends with safety follow up visit/end of study, 30-35 days after the last intake to the study drug.
All subjects who prematurely and definitively discontinue study drug before Week 42 must have a premature EOT visit as soon as possible but no later than 7 days after the decision of definitive discontinuation of study drug and have a safety follow-up visit as described above.
Post-Treatment Observational Period: Subjects are to remain in the study after premature EOT and safety visit and undergo all study assessments up to Week 42, except subjects discontinuing study drug due to PH-related disease progression who will have a premature EOT visit and Safety follow-up visit and will be withdrawn from the study.
A total of 96 newly diagnosed and treatment-naïve subjects with inoperable CTEPH will be randomly assigned in a 1:1 ratio to receive either macitentan (n=48) or placebo (n=48) combined with standard of care with riociguat.
- Being tested
- Macitentan 10mg, Placebo
- Medical subject headings
- Chronic Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macitentan 10mgDrug
Macitentan 10 mg will be initiated at Day 8 (+/- 3 days) until week 42 (+/- week). The recommended dose is 10 mg once daily by oral administration
PlaceboDrug
Placebo 10 mg will be initiated at Day 8 (+/- 3 days) until week 42 (+/- week). The recommended dose is 10 mg once daily by oral administration
| Study group | Role | What they receive |
|---|---|---|
| Control Arm | Placebo comparator | Oral Standard-of care riociguat from Day 1 to Week 42 (+/- 1 week). Posology 1mg tid - 2,5 mg tid. Oral Placebo 10 mg/day from Day 8 (+/- 3 days) to Week 42 (+/- 1 week). At week 16, subjects who are still symptomatic (WHO functional II to IV) and have PVR ≥ 240 dyn.sec.cm-5 will be offered additional treatment by BPA. Receives: Drug: Placebo |
| Experimental Arm | Experimental | Oral Standard-of care riociguat from Day 1 to Week 42 (+/- 1 week). Posology 1mg tid - 2,5 mg tid. Oral Macitentan 10 mg/day from Day 8 (+/- 3 days) to Week 42 (+/- 1 week). At week 16, subjects who are still symptomatic (WHO functional II to IV) and have PVR ≥ 240 dyn.sec.cm-5 will be offered additional treatment by BPA. Receives: Drug: Macitentan 10mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Pulmonary vascular resistance (PVR) at rest at week 16 expressed as a percentage of the baseline resting PVR.
Measured: Week 16
Secondary outcomes (15)
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Change from Baseline to Week 16 in 6 Minutes Walk Distance Test
Measured: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Change from Baseline to Week 16 in World Health Organization Functional Classification
Measured: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Change from Baseline to Week 16 in Borg dyspnea score
Measured: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Change from Baseline to Week 16 in NT pro-BNP level
Measured: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on quality of life prior to BPA
Change from Baseline to Week 16 in EuroQol-5D-3Level scale
Measured: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Change from Baseline to Week 42 in 6 Minutes Walk Distance Test
Measured: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Change from Baseline to Week 42 in World Health Organization Functional Classification
Measured: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Change from Baseline to Week 42 in Borg dyspnea score
Measured: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Change from Baseline to Week 42 in NT pro BNP level
Measured: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on quality of life after potential BPA
Change from Baseline to Week 42 in EuroQol-5D-3Level scale
Measured: Week 42
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 after potential BPA
Change from baseline to week 42 in PVR and percentage of subjects reaching PVR<240 dyn.sec.cm-5 at week 42.
Measured: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on the rate of BPA procedure-related complications
Frequency and type of BPA procedure-related complications from BPA procedure to end-of-study
Measured: Immediately after intervention
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on the disease progression
Time from randomization to the first PH-related disease progression event up to end-of-study, defined as any of the following :
Death (all causes), Need for lung transplantation, Hospitalization due to PH, Initiation of parenteral prostanoid therapy due to PH-related disease progression
, Worsening defined as a post-baseline decrease in 6MWD by ≥ 15 % combined with WHO FC III or IV).
Measured: Week 42
Recording of serious and non serious adverse events/effects, Treatment-emergent adverse events (AEs) and serious adverse events (SAEs), AEs leading to premature discontinuation of study drug
Measured: Week 42
Change from baseline in laboratory variable, weight and vital signs o Change from baseline in laboratory variables o Change from baseline in weight and vital signs (arterial blood pressure, heart rate).
Measured: Week 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start14 Jun 2021
- Primary completion3 Jul 2025
- Study completion3 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thromboembolic Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP
- Responsible party
- Sponsor
- Investigators
- Xavier JAIS, Dr, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04780932
- Sponsor's protocol ID
- APHP201037
- Acronym
- IMPACT-CTEPH
- Status last verified
- Jul 2025
- First submitted
- 15 Feb 2021
- Last updated
- 20 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Initial Dual Oral coMbination Therapy Versus Standard-of-care Initial Oral Monotherapy Prior to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary hyperTension
- ClinicalTrials.gov ID
- NCT04780932
- Acronym / sponsor ID
- IMPACT-CTEPH / APHP201037
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Janssen, LP
- Study start
- 14 Jun 2021 (actual)
- Primary completion
- 3 Jul 2025 (actual)
- Study completion
- 3 Jul 2025 (actual)
- First posted
- 4 Mar 2021 (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.
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by an obstruction of proximal or more distal pulmonary arteries by residual organized thrombi, combined with a variable microscopic pulmonary vasculopathy (microvasculopathy). Besides lifelong anticoagulation, surgical pulmonary endarterectomy is the treatment of choice in subjects with proximal CTEPH affecting large pulmonary arteries. However, around half of CTEPH subjects are not operated, mainly because of distal lesions inaccessible to surgery. International data have reported survival rates of 88, 79, and 70% at 1, 2, and 3 years, respectively, in subjects with inoperable CTEPH, underscoring the need for better treatment strategies. In those subjects, current guidelines recommend medical therapy with or without balloon pulmonary angioplasty (BPA). Currently, only one drug (riociguat), targeting the NO pathway, is approved and reimbursed in Europe. Thus, riociguat monotherapy is considered as the standard-of-care treatment for subjects newly diagnosed with inoperable CTEPH. Recently, macitentan, targeting the endothelin-1 pathway, showed to be also effective in subjects with inoperable CTEPH. However, macitentan is currently not approved for CTEPH in Europe.
BPA has been also reported to improve hemodynamics, symptoms and exercise capacity. However, complications, including mainly vascular injury, may occur during this procedure and it has been shown that the risk of BPA-related complications was strongly related to the level of pre-BPA mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). Medical therapy and BPA have in fact complementary effects since they target different lesions. Indeed, BPA targets fibrotic organized thrombi in the segmental arteries down to small pulmonary arteries of 2-5 mm in diameter. Medical therapy, for its part, targets microvasculopathy, similar to that observed in pulmonary arterial hypertension (PAH), in vessels less than 0.5 mm in diameter. Therefore, it is strongly believed that the use of medical therapy prior to BPA may reduce the risk of BPA-related complications by improving pulmonary hemodynamics and may improve global efficacy. In PAH, initial dual oral combination therapy with drugs targeting the NO and endothelin pathways is considered as a standard of care, more efficacious than monotherapy and safe. In contrast, there are no data from controlled trials regarding the efficacy and safety of initial combination therapy regimens versus standard-of-care monotherapy in treatment-naïve subjects with inoperable CTEPH.
The investigators hypothesize that initial dual oral combination therapy may be superior to standard-of-care riociguat monotherapy for improving pulmonary hemodynamics prior to BPA and for reducing the risk of BPA-related complications.
Detailed description
The Screening period will last up 28 days maximum. It begins at the first screening assessment and ends with subject inclusion. The Screening visit date is the date when the first screening assessment is performed.
The Treatment period will start at Day 1 with the first dose of riociguat and ends at Week 42 / End-of-Treatment (EOT) visit.
On Day 8, the experimental treatment with macitentan / placebo will be started.
During this period, regular hospital visits will be performed (Week 16, Week 29).
In addition, laboratory tests will be performed every 4 weeks as part of standard of care.
Subjects who are still symptomatic (WHO FC II to IV) and have PVR≥ 240 dyn.sec.cm-5 at week 16 will be offered additional treatment by BPA.
Safety follow-up period: After study drug discontinuation, all subjects will enter a Safety follow-up period which ends with safety follow up visit/end of study, 30-35 days after the last intake to the study drug.
All subjects who prematurely and definitively discontinue study drug before Week 42 must have a premature EOT visit as soon as possible but no later than 7 days after the decision of definitive discontinuation of study drug and have a safety follow-up visit as described above.
Post-Treatment Observational Period: Subjects are to remain in the study after premature EOT and safety visit and undergo all study assessments up to Week 42, except subjects discontinuing study drug due to PH-related disease progression who will have a premature EOT visit and Safety follow-up visit and will be withdrawn from the study.
A total of 96 newly diagnosed and treatment-naïve subjects with inoperable CTEPH will be randomly assigned in a 1:1 ratio to receive either macitentan (n=48) or placebo (n=48) combined with standard of care with riociguat.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Arm | Placebo comparator | Drug: PlaceboOral Standard-of care riociguat from Day 1 to Week 42 (+/- 1 week). Posology 1mg tid - 2,5 mg tid. Oral Placebo 10 mg/day from Day 8 (+/- 3 days) to Week 42 (+/- 1 week). At week 16, subjects who are still symptomatic (WHO functional II to IV) and have PVR ≥ 240 dyn.sec.cm-5 will be offered additional treatment by BPA. |
| Experimental Arm | Experimental | Drug: Macitentan 10mgOral Standard-of care riociguat from Day 1 to Week 42 (+/- 1 week). Posology 1mg tid - 2,5 mg tid. Oral Macitentan 10 mg/day from Day 8 (+/- 3 days) to Week 42 (+/- 1 week). At week 16, subjects who are still symptomatic (WHO functional II to IV) and have PVR ≥ 240 dyn.sec.cm-5 will be offered additional treatment by BPA. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- 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:
Key exclusion criteria (26 listed)
- Previous pulmonary endarterectomy.
- Previous balloon pulmonary angioplasty.
- 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).
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 |
|---|---|---|
| Macitentan 10mgMacitentan 10 mg will be initiated at Day 8 (+/- 3 days) until week 42 (+/- week). The recommended dose is 10 mg once daily by oral administration | Drug | Experimental Arm |
| PlaceboPlacebo 10 mg will be initiated at Day 8 (+/- 3 days) until week 42 (+/- week). The recommended dose is 10 mg once daily by oral administration | Drug | Control Arm |
Primary outcome
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.
Time frame: Week 16
Pulmonary vascular resistance (PVR) at rest at week 16 expressed as a percentage of the baseline resting PVR.
15 secondary outcomes
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Time frame: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Time frame: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Time frame: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension prior to BPA
Time frame: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on quality of life prior to BPA
Time frame: Week 16
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Time frame: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Time frame: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Time frame: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on other clinical measures of pulmonary hypertension after potential BPA
Time frame: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on quality of life after potential BPA
Time frame: Week 42
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 after potential BPA
Time frame: Week 42
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on the rate of BPA procedure-related complications
Time frame: Immediately after intervention
To compare the effect of an initial dual oral treatment (riociguat, macitentan) vs. standard-of-care initial oral monotherapy (riociguat, placebo) on the disease progression
Time frame: Week 42
Recording of serious and non serious adverse events/effects, Treatment-emergent adverse events (AEs) and serious adverse events (SAEs), AEs leading to premature discontinuation of study drug
Time frame: Week 42
Change from baseline in laboratory variable, weight and vital signs o Change from baseline in laboratory variables o Change from baseline in weight and vital signs (arterial blood pressure, heart rate).
Time frame: Week 42
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2025.
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Chronic Pulmonary Thromboembolism
Recruiting
The Effect of Levosimendan on Pulmonary Artery Pressure and Right Ventricular Function in the Perioperative Period in Patients With CTEPH After Pulmonary Thromboendarterectomy
LEVOSIMENDAN, PULMONARY THROMBOENDARTERECTOMY
RecruitingPhase 3
A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option
Hypertension, Pulmonary
Recruiting
Vasopressor Agents in Pulmonary Hypertension Crisis
Pulmonary Arterial Hypertension (PAH), Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
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. This study is not recruiting at the moment.
Xavier JAIS, Dr principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Macitentan 10mg in people with Thromboembolic Pulmonary Hypertension and Chronic Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 16 inclusion and 26 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: finished, as of the sponsor's last update on 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jul 2025.