Ignite Creation Date:
2024-05-06 @ 3:51 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04780932
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2021-02-15
Brief 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
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMPACT-CTEPH
Brief 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 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 05 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
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 05 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 dynseccm-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 visitend 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 11 ratio to receive either macitentan n48 or placebo n48 combined with standard of care with riociguat
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 dynseccm-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 visitend 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 11 ratio to receive either macitentan n48 or placebo n48 combined with standard of care with riociguat
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None