BPA vs. PEA in CTEPH

Study Overview
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Brief Summary
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Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and potentially life-threatening progressive disease that evolves from unresolved pulmonary embolism. Gold standard treatment for CTEPH is pulmonary endarterectomy (PEA) performed by skilled cardio-thoracic surgeons. Some patients may not be surgical candidates due to co-morbidities or because the vascular lesions are too distal making them technically inoperable. In these patients, balloon pulmonary angioplasty (BPA) has emerged as an effective treatment. In a subgroup of patients, the distribution of vascular lesions makes it possible to perform either BPA or PEA. There has never been a head-to head comparison of BPA with PEA. The aim of this study is therefore, to evaluate if BPA is non-inferior to PEA in patients with (CTEPH) who are eligible for both treatments.

Detailed Description
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An investigator-initiated multicenter, prospective, randomized, controlled, open label, non-inferiority trial. The study will randomize (1:1) 152 patients with CTEPH who are eligible for both PEA and BPA. Patients will be screened for study inclusion at the local CTEPH multidisciplinary team conference and eligibility for both PEA and BPA will be confirmed by a central adjudication committee. PEA or BPA will be completed within 6 months from randomization. Follow-up visit with right heart catheterization will be completed at 4 months and 12 months after PEA or last BPA session. Primary end-point is change in pulmonary vascular resistance from baseline to 4 months and 12 months after PEA or the last BPA session.

Official Title
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Balloon Pulmonary anGiOplasty Versus Pulmonary Endarterectomy in Patients With Chronic ThromboEmbolic Pulmonary Hypertension: a Non-inferiority Randomized Trial

Conditions
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Chronic Thromboembolic Pulmonary Hypertension

Intervention / Treatment
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* Procedure: Pulmonary endarterectomy
* Procedure: Balloon pulmonary angioplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with chronic thromboembolic pulmonary hypertension according to current European society of cardiology/European Respiratory Society guidelines and eligible for both pulmonary endarterectomy and ballon pulmonary angioplasty by decision at the local multidisciplinary team conference and central adjudication committee Written informed consent from the patient Patient age >17 and <80 years Able to understand and follow instructions and to participate in the entire study period Exclusion Criteria: Life expectancy <12 months Co morbidities evaluated at the multidisciplinary team conference, that contributes significantly to the patients pulmonary hypertension Not possible to perform balloon pulmonary angioplasty or pulmonary endarterectomy within 4 months after randomization. Evaluated at multidisciplinary team conference that changes in pulmonary artery hypertension targeted therapy between baseline and 4 months follow-up is inevitable* Known pregnancy or positive urine Human chorionic gonadotropin screening test in fertile women Previous balloon pulmonary angioplasty or pulmonary endarterectomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BPA group<br>Balloon pulmonary angioplasty. Typically 4-8 sessions are needed to treat the patient. The specific pre-planning protocol, choice of wires and balloons, the number of vessels treated per session, and the decision that no further BPA sessions are needed is at the discretion of the treating physician. | Procedure: Balloon pulmonary angioplasty<br>* Percutaneous balloon pulmonary angioplasty is performed using standard percutaneous technique to break the fibrotic clots in the pulmonary arteries using percutaneous transluminal angioplasty balloons.<br>|
| Active Comparator: PEA group<br>Patients randomized to PEA will undergo surgery within 4 months after randomization and optional run-in phase. Distality of the dissection plane is at the discretion of the operating physicians. | Procedure: Pulmonary endarterectomy<br>* Surgical pulmonary endarterectomy is done by a thoracic surgical procedure by removing chronic thrombotic material by intimal dissection with patient on cardiopulmonary bypass.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulmonary vascular resistance | Change in pulmonary vascular resistance from baseline to 4-months and 12-months after the procedure(s). Patients on medical treatments at baseline will remain on medical treatments until the assessment of the primary endpoint, and be taken off if hemodynamics permit | 4 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean pulmonary artery pressure | Mean pulmonary artery pressure measured by right heart catheterization | 4 months and 12 months | 
| Cardiac index | Cardiac index measured by right heart catheterization | 4 months and 12 months | 
| Mean right atrial pressure | Right atrial pressure measured by right heart catheterization | 4 months and 12 months | 
| Six minutes walking distance | Six minutes walking distance | 4 months and 12 months | 
| Time to clinical worsening | Clinical worsening includes all-cause mortality, nonelective hospitalization for pulmonary artery hypertension, and disease progression (disease progression is defined as a reduction from baseline in the six minutes walking distance by 15% plus worsening functional class (except for patients already in Orld health organization functional class IV).) | 4 months and 12 months | 
| N-terminal pro B-type natriuretic peptide | N-terminal pro B-type natriuretic peptide | 4 months and 12 months | 
| Quality of life evaluated by the Living with pulmonary hypertension questionnaire | Measured by the use of Living with pulmonary hypertension questionnaire (21 questions scored 0-5. Minimum score is 0 and maximum score is 105. Low score means high quality of life and a high score means a low quality of life). | 4 months and 12 months |