'Thrombectomy in High-Risk Pulmonary Embolism - Device Versus Thrombolysis Netherlands': TORPEDO-NL

Summary

TORPEDO-NL will be an investigator-initiated, academically sponsored, multicentre, open-label, randomized controlled trial (RCT). Patients with high-risk pulmonary embolism (PE) require immediate reperfusion therapy on top of anticoagulation. The standard reperfusion treatment in these patients is full-dose systemic thrombolysis. This carries a significant risk of major bleeding (10-25%) and intracranial haemorrhage (ICH, 3%). Catheter-directed thrombectomy (CDT) is a promising alternative to systemic thrombolysis with a more direct effect on reducing pulmonary artery clot burden and very likely a better safety profile. Randomized trials evaluating the safety and efficacy of CDT in high-risk patients are currently unavailable. The investigators hypothesize that in high-risk PE patients, CDT is superior to the current standard of systemic thrombolysis in terms of mortality and adverse events, i.e., is associated with a lower composite incidence of all-cause mortality, treatment failure, major bleeding and all-cause stroke. The investigators also hypothesize that CDT will lead to a shorter length of stay (LOS) at the intensive care unit (ICU) and in-hospital, faster recovery, and better long-term quality of life (QoL). Objective: To determine whether CDT in high-risk PE relative to systemic thrombolysis is: * more effective and safer in terms of a reduction of the composite endpoint on all-cause mortality and adverse events defined as treatment failure, major bleeding and all-cause stroke at day 30 (primary outcome) * leads to a better Desirability of Outcome Ranking (DOOR) at day 7 * associated with a lower level of oxygen supplementation at 48 hours * associated with shorter length of stay (LOS) at the intensive care unit (ICU) and in the hospital * associated with better functional recovery as well as better patient-reported outcomes such as QoL at one year * cost-effective after a time horizon of one year

Timeline

Start

2025-02

Primary completion

2028-01

Completion

2029-01

Publications

• Background Arora S, Vallabhajosyula S, Aggarwal V, Basir MB, Kelly B, Atreya AR. Novel Risk Stratification and Hemodynamic Profiling in Acute Pulmonary Embolism: A Proposed Classification Inspired by Society for Cardiovascular Angiography and Intervention Shock Staging. Interv Cardiol Clin. 2023 Jul;12(3S):e1-e20. doi: 10.1016/j.iccl.2024.04.002. Epub 2024 May 25.
• Background Kapur NK, Kanwar M, Sinha SS, Thayer KL, Garan AR, Hernandez-Montfort J, Zhang Y, Li B, Baca P, Dieng F, Harwani NM, Abraham J, Hickey G, Nathan S, Wencker D, Hall S, Schwartzman A, Khalife W, Li S, Mahr C, Kim JH, Vorovich E, Whitehead EH, Blumer V, Burkhoff D. Criteria for Defining Stages of Cardiogenic Shock Severity. J Am Coll Cardiol. 2022 Jul 19;80(3):185-198. doi: 10.1016/j.jacc.2022.04.049.
• Background Gwozdz AM, de Jong CMM, Fialho LS, Likitabhorn T, Sossi F, Jaber PB, Hojen AA, Arcelus JI, Auger WR, Ay C, Barco S, Gazzana MB, Bayley J, Bertoletti L, Cate-Hoek AT, Cohen AT, Connors JM, Galanaud JP, Labropoulos N, Langlois N, Meissner MH, Noble S, Nossent EJ, de Leon Lovaton PP, Robert-Ebadi H, Rosovsky RP, Smolenaars N, Toshner M, Tromeur C, Wang KL, Westerlund E, de Wit K, Black SA, Klok FA. Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation. Lancet Haematol. 2022 Sep;9(9):e698-e706. doi: 10.1016/S2352-3026(22)00215-0.
• Background Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25.
• Background Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
• Background Ende-Verhaar YM, Meijboom LJ, Kroft LJM, Beenen LFM, Boon GJAM, Middeldorp S, Nossent EJ, Symersky P, Huisman MV, Bogaard HJ, Vonk Noordegraaf A, Klok FA. Usefulness of standard computed tomography pulmonary angiography performed for acute pulmonary embolism for identification of chronic thromboembolic pulmonary hypertension: results of the InShape III study. J Heart Lung Transplant. 2019 Jul;38(7):731-738. doi: 10.1016/j.healun.2019.03.003. Epub 2019 Mar 15.
• Background Kabrhel C, Okechukwu I, Hariharan P, Takayesu JK, MacMahon P, Haddad F, Chang Y. Factors associated with clinical deterioration shortly after PE. Thorax. 2014 Sep;69(9):835-42. doi: 10.1136/thoraxjnl-2013-204762. Epub 2014 May 20.
• Background Pancani R, Villari L, Aquilini F, Palla A, Carrozzi L, Celi A. Prognostic role of respiratory failure in acute pulmonary embolism: a prospective multicenter study. Thromb Res. 2022 Sep;217:33-35. doi: 10.1016/j.thromres.2022.07.002. Epub 2022 Jul 9. No abstract available.
• Background Ergan B, Ergun R, Caliskan T, Aydin K, Tokur ME, Savran Y, Koca U, Comert B, Gokmen N. Mortality Related Risk Factors in High-Risk Pulmonary Embolism in the ICU. Can Respir J. 2016;2016:2432808. doi: 10.1155/2016/2432808. Epub 2016 Nov 29.
• Background Koslow M, Epstein Shochet G, Fenadka F, Neuman Y, Osadchy A, Shitrit D. Systemic Thrombolysis Therapy is Associated With Improved Outcomes Among Patients With Acute Pulmonary Embolism and Respiratory Failure. Am J Med Sci. 2020 Aug;360(2):129-136. doi: 10.1016/j.amjms.2020.04.028. Epub 2020 Apr 28.
• Background Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ni Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. No abstract available.
• Background Huisman MV, Barco S, Cannegieter SC, Le Gal G, Konstantinides SV, Reitsma PH, Rodger M, Vonk Noordegraaf A, Klok FA. Pulmonary embolism. Nat Rev Dis Primers. 2018 May 17;4:18028. doi: 10.1038/nrdp.2018.28.
• Stenger WJE, den Uil CA, Rietdijk WJR, Al Amri I, Montero-Cabezas JM, Elzo Kraemer CV, van Mens TE, Meuwese CL, van Mieghem NMDA, Lauw MN, van den Toorn LM, Levolger S, van de Luijtgaarden KM, Sprenger RA, van Dongen JM, Imani F, Meuwissen M, Kant KM, Aarts RAHM, Winckers K, Brans RJB, Kuiper GJAJM, Schnabel R, Ende-Verhaar YM, Urlings TAJ, Ruys TA, Slot S, Scheffer HJ, Adriaansens SOJH, Boomsma MF, Nijholt IM, Walen S, Leentjens J, Jenniskens S, van Geuns RJ, Griffioen A, Nijkeuter M, Ruigrok D, Vos JA, Kies DA, Tuinman PR, Lely RJ, van der Meijs BB, Hovens MMC, Konstantinides SV, Mol MS, Kraaijeveld AO, Klok FA; Contributing authors. Thrombectomy in high-risk pulmonary embolism - device versus thrombolysis: rationale and design of the TORPEDO-NL investigator-initiated, academically-sponsored, multicenter, open-label randomized controlled trial. Thromb Res. 2025 Nov;255:109420. doi: 10.1016/j.thromres.2025.109420. Epub 2025 Aug 7.

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