BPA vs. PEA in CTEPH

NCT05110066 | Recruiting DMC

• 1 other identifier: 190580-0002
• Study Type: interventional
• Target: 139
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Mean pulmonary artery pressure

  4 months and 12 months

• Cardiac index

  4 months and 12 months

• Mean right atrial pressure

  4 months and 12 months

• Six minutes walking distance

  4 months and 12 months

• Time to clinical worsening

  4 months and 12 months

Other Outcomes (3)

• Peri-operative/peri-interventional complications

  30 days

• Total length of hospital stay in both groups

  4 month

• Median survival at 12 month

  12 months

Study Arms (2)

BPA group

ACTIVE COMPARATOR

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

PEA group

ACTIVE COMPARATOR

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

Interventions

Pulmonary endarterectomy PROCEDURE

Surgical pulmonary endarterectomy is done by a thoracic surgical procedure by removing chronic thrombotic material by intimal dissection with patient on cardiopulmonary bypass.

PEA group

Balloon pulmonary angioplasty PROCEDURE

Percutaneous balloon pulmonary angioplasty is performed using standard percutaneous technique to break the fibrotic clots in the pulmonary arteries using percutaneous transluminal angioplasty balloons.

BPA group

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead
• Kerckhoff Klinik: collaborator
• Medical University of Vienna: collaborator
• Papworth Hospital NHS Foundation Trust: collaborator
• St. Antonius Hospital: collaborator
• Utrecht University: collaborator
• KU Leuven: collaborator
• Amsterdam UMC, location VUmc: collaborator

Study Sites (2)

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Royal Ppworth

Cambridge, United Kingdom

RECRUITING

Related Publications (14)

• Lang IM, Pesavento R, Bonderman D, Yuan JX. Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding. Eur Respir J. 2013 Feb;41(2):462-8. doi: 10.1183/09031936.00049312. Epub 2012 Jun 14.

  PMID: 22700839 BACKGROUND

• Gall H, Hoeper MM, Richter MJ, Cacheris W, Hinzmann B, Mayer E. An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan. Eur Respir Rev. 2017 Mar 29;26(143):160121. doi: 10.1183/16000617.0121-2016. Print 2017 Mar 31.

  PMID: 28356407 BACKGROUND

• Gerges C, Gerges M, Friewald R, Fesler P, Dorfmuller P, Sharma S, Karlocai K, Skoro-Sajer N, Jakowitsch J, Moser B, Taghavi S, Klepetko W, Lang IM. Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension: Hemodynamic Phenotyping and Histomorphometric Assessment. Circulation. 2020 Feb 4;141(5):376-386. doi: 10.1161/CIRCULATIONAHA.119.041515. Epub 2020 Jan 3.

  PMID: 31896275 BACKGROUND

• Delcroix M, Vonk Noordegraaf A, Fadel E, Lang I, Simonneau G, Naeije R. Vascular and right ventricular remodelling in chronic thromboembolic pulmonary hypertension. Eur Respir J. 2013 Jan;41(1):224-32. doi: 10.1183/09031936.00047712. Epub 2012 Aug 16.

  PMID: 22903956 BACKGROUND

• Riedel M, Stanek V, Widimsky J, Prerovsky I. Longterm follow-up of patients with pulmonary thromboembolism. Late prognosis and evolution of hemodynamic and respiratory data. Chest. 1982 Feb;81(2):151-8. doi: 10.1378/chest.81.2.151.

  PMID: 7056079 BACKGROUND

• Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015 Oct;46(4):903-75. doi: 10.1183/13993003.01032-2015. Epub 2015 Aug 29.

  PMID: 26318161 BACKGROUND

• Jenkins D, Madani M, Fadel E, D'Armini AM, Mayer E. Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension. Eur Respir Rev. 2017 Mar 15;26(143):160111. doi: 10.1183/16000617.0111-2016. Print 2017 Jan.

  PMID: 28298388 BACKGROUND

• Pepke-Zaba J, Delcroix M, Lang I, Mayer E, Jansa P, Ambroz D, Treacy C, D'Armini AM, Morsolini M, Snijder R, Bresser P, Torbicki A, Kristensen B, Lewczuk J, Simkova I, Barbera JA, de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA, Kovacs G, Hamid AM, Jais X, Simonneau G. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation. 2011 Nov 1;124(18):1973-81. doi: 10.1161/CIRCULATIONAHA.110.015008. Epub 2011 Oct 3.

  PMID: 21969018 BACKGROUND

• Lang I, Meyer BC, Ogo T, Matsubara H, Kurzyna M, Ghofrani HA, Mayer E, Brenot P. Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Eur Respir Rev. 2017 Mar 29;26(143):160119. doi: 10.1183/16000617.0119-2016. Print 2017 Mar 31.

  PMID: 28356406 BACKGROUND

• Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D'Armini AM, Snijder R, Bresser P, Torbicki A, Mellemkjaer S, Lewczuk J, Simkova I, Barbera JA, de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA, Kovacs G, Jais X, Ambroz D, Treacy C, Morsolini M, Jenkins D, Lindner J, Dartevelle P, Mayer E, Simonneau G. Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry. Circulation. 2016 Mar 1;133(9):859-71. doi: 10.1161/CIRCULATIONAHA.115.016522. Epub 2016 Jan 29.

  PMID: 26826181 BACKGROUND

• Khan MS, Amin E, Memon MM, Yamani N, Siddiqi TJ, Khan SU, Murad MH, Mookadam F, Figueredo VM, Doukky R, Benza RL, Krasuski RA. Meta-analysis of use of balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension. Int J Cardiol. 2019 Sep 15;291:134-139. doi: 10.1016/j.ijcard.2019.02.051. Epub 2019 Feb 23.

  PMID: 30850238 BACKGROUND

• Tanabe N, Kawakami T, Satoh T, Matsubara H, Nakanishi N, Ogino H, Tamura Y, Tsujino I, Ogawa A, Sakao S, Nishizaki M, Ishida K, Ichimura Y, Yoshida M, Tatsumi K. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: A systematic review. Respir Investig. 2018 Jul;56(4):332-341. doi: 10.1016/j.resinv.2018.03.004. Epub 2018 Jul 3.

  PMID: 30008295 BACKGROUND

• Kim NH, Delcroix M, Jenkins DP, Channick R, Dartevelle P, Jansa P, Lang I, Madani MM, Ogino H, Pengo V, Mayer E. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D92-9. doi: 10.1016/j.jacc.2013.10.024.

  PMID: 24355646 BACKGROUND

• Mayer E, Jenkins D, Lindner J, D'Armini A, Kloek J, Meyns B, Ilkjaer LB, Klepetko W, Delcroix M, Lang I, Pepke-Zaba J, Simonneau G, Dartevelle P. Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. J Thorac Cardiovasc Surg. 2011 Mar;141(3):702-10. doi: 10.1016/j.jtcvs.2010.11.024.

  PMID: 21335128 BACKGROUND

Study Officials

• Irene Lang, MD,Prof

  Medical University of Vienna

  STUDY CHAIR

• Harm Jan Bogaard, MD, Prof.

  Amsterdam University Medical Center

  STUDY CHAIR

• Marion Delcroix, MD, Prof.

  KU Leuven

  STUDY CHAIR

• Marco Post, MD, Prof.

  St. Antonius Hospital

  STUDY CHAIR

• Gregely Meszaros, MD

  Pulmonary Hypertension Association Europe

  STUDY CHAIR

• Johanna Pepke-Zaba, MD, Prof.

  Papworth Hospital NHS Foundation Trust

  STUDY CHAIR

• Christoph Wiedenroth, MD

  Kerckhoff Klinik

  STUDY CHAIR

Central Study Contacts

Asger Andersen, MD, ass.prof.

CONTACT

40138052; asger.andersen@clin.au.dk

Kristina Laut Matzen, RN,PhD

CONTACT

+4521673903; krlaut@clin.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: November 5, 2021
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR

Locations

DK (1); GB (1)