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

NCT ID: NCT06833827

Last Updated: 2025-02-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

111 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-28

Study Completion Date

2029-01-31

Brief Summary

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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

Detailed Description

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Conditions

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Pulmonary Embolism Acute

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Catheter-directed thrombectomy (CDT)

Patients in the intervention group will receive Catheter-directed thrombectomy (CDT).

Group Type EXPERIMENTAL

Catheter-directed thrombectomy (CDT)

Intervention Type DEVICE

The intervention consists of immediate thrombectomy (thrombectomy with any approved device) without systemic/locally administered thrombolysis. Thrombectomy is performed via jugular or femoral venous access according to the instructions for use for the particular device. The catheter is advanced over a preplaced guidewire across the right heart into the pulmonary arteries to the location of proximal thrombus. Procedural therapeutic anticoagulation with heparin is administered. After removal of the dilator, the thrombus is extracted by controlled volume aspiration through an aspiration catheter using a syringe or dedicated aspiration system, with multiple aspirations performed as needed. Procedural objectives will be clearly stated prior to the intervention and patient's clinical and hemodynamic status and residual thrombus will guide the investigators to determine when to terminate the procedure. Treatment success is defined as clear evidence of right ventricular recompensation.

Systemic Thrombolysis

Patients in the control group will receive full-dose systemic thrombolysis.

Group Type ACTIVE_COMPARATOR

thrombolysis therapy

Intervention Type DRUG

Standard reperfusion treatment for high-risk PE patients is thrombolytic therapy, typically consisting of Alteplase, Urokinase, or Tenecteplase, with the idea of accelerated fragmentation of the thrombus by lytic medication given systemically.

Interventions

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Catheter-directed thrombectomy (CDT)

The intervention consists of immediate thrombectomy (thrombectomy with any approved device) without systemic/locally administered thrombolysis. Thrombectomy is performed via jugular or femoral venous access according to the instructions for use for the particular device. The catheter is advanced over a preplaced guidewire across the right heart into the pulmonary arteries to the location of proximal thrombus. Procedural therapeutic anticoagulation with heparin is administered. After removal of the dilator, the thrombus is extracted by controlled volume aspiration through an aspiration catheter using a syringe or dedicated aspiration system, with multiple aspirations performed as needed. Procedural objectives will be clearly stated prior to the intervention and patient's clinical and hemodynamic status and residual thrombus will guide the investigators to determine when to terminate the procedure. Treatment success is defined as clear evidence of right ventricular recompensation.

Intervention Type DEVICE

thrombolysis therapy

Standard reperfusion treatment for high-risk PE patients is thrombolytic therapy, typically consisting of Alteplase, Urokinase, or Tenecteplase, with the idea of accelerated fragmentation of the thrombus by lytic medication given systemically.

Intervention Type DRUG

Other Intervention Names

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CDT Thrombectomy catheter-directed mechanical thrombectomy mechanical thrombectomy Catheter-based thrombectomy systemic thrombolysis full-dose systemic thrombolysis thrombolysis thrombolytic therapy

Eligibility Criteria

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Inclusion Criteria

1. Adult patients with confirmed acute PE, i.e. contrast filling defect in a lobar or more proximal pulmonary artery on computed tomography pulmonary angiography (CTPA), and/or obstructive shock with echocardiographic confirmed dilatation of the right ventricle and a congested vena cava inferior, both with/without echocardiographic signs of clot in transit or deep vein thrombosis of the leg.
2. High risk for mortality, i.e.

1. post cardiac arrest (after temporary need for cardiopulmonary resuscitation), OR
2. obstructive shock (systolic blood pressure \<90 mmHg and signs of end-organ hypoperfusion (e.g. elevated lactate levels \>2 mmol/l) or the need for vasopressors (adrenalin or noradrenalin) to maintain an adequate blood pressure), OR
3. persistent hypotension (systolic blood pressure \<90 mmHg or systolic blood pressure drop ≥40 mmHg for at least 15 minutes) not caused by new onset arrhythmia, hypovolemia, or sepsis, OR
4. abnormal RV function on transthoracic echocardiography or CTPA AND elevated cardiac troponin levels AND respiratory failure defined as hypoxemia (SaO2 \<90%) refractory to O2 supplementation by nasal cannula or Venturi mask, requiring full face mask O2 supplementation (100% FiO2), high-flow nasal O2, or (non-)invasive mechanical ventilation.
3. CDT available and technically feasible so as to allow for a randomization-to-needle time of 60 minutes or less.

Exclusion Criteria

1. "Catastrophic PE", i.e. ongoing cardiac arrest and/or need for extracorporeal cardiopulmonary resuscitation (ECPR) and/or immediate indication for venoarterial extracorporeal membrane oxygenation (VA-ECMO) as judged by the responsible physician(s)
2. Glascow Coma Scale \<8 following resuscitation for cardiac arrest
3. Alternative diagnosis than acute PE contributing largely to the acute hemodynamic and/or respiratory failure, e.g. sepsis, COPD GOLD 3 or 4, or known heart failure with NYHA Functional Classification of 4, as judged by the treating physician.
4. A known "do not admit to the ICU" or "do not resuscitate" directive
5. An absolute contraindication to systemic thrombolysis, i.e.

* History of hemorrhagic stroke
* Ischemic stroke in past 6 months
* Central nervous system neoplasm
* Major trauma, major surgery or major head injury in past 3 weeks (note: mild external laceration of the head after, e.g. syncope, does not count as major head injury, especially when a CT scan of the head shows no hematoma)
* Active bleeding, life-threatening or into a critically organ/area; OR known severe bleeding diathesis with previous bleeding fulfilling these criteria
6. Reperfusion therapy (systemic thrombolysis, surgical thrombectomy or CDT/other catheter directed therapy), or placement of a non-retrieved inferior vena cava filter for acute pulmonary embolism in the past 3 months
7. Thrombus in transit through a patent foramen ovale.
8. Known chronic thromboembolic pulmonary hypertension (CTEPH), or strong suspicion of CTEPH based on pre-existing clinical findings and combinations of signs of PE chronicity on echocardiography and/or CTPA.
9. Known hypersensitivity to systemic thrombolysis, heparin, or to any of the excipients
10. If, in the Investigator's opinion, or after consultation with the local PERT-team or EC-members, the patient is not appropriate for thrombectomy
11. Chronic use of full-dose oral or parenteral anticoagulation before presentation.
12. Pregnancy
13. Current participation in another study that would interfere with participation in this study
14. Previous enrolment in this study
15. Refusal of deferred consent by the next of kin or by the patient himself to use the data. Deferred consent will not be asked to relatives of patients who die in scene, but are included in the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Heart Foundation

OTHER

Sponsor Role collaborator

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Zorginstituut Nederland: The Health Care Insurance Board

UNKNOWN

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Erik Klok

Clinical Professsor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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F. A. Klok, Prof. MD. PhD.

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

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Leiden University Medical Centre

Leiden, South Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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W. J.E. Stenger, MD

Role: CONTACT

0031-71-52698096

F. A. Klok, Prof. MD. PhD.

Role: CONTACT

0031-71-5263761

Facility Contacts

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F A Klok, MD, PhD, Prof

Role: primary

0031715298096

Justine JE Stenger, MD

Role: backup

0031715298096

References

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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.

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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.

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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.

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Reference Type BACKGROUND
PMID: 35849919 (View on PubMed)

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.

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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.

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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.

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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.

Reference Type BACKGROUND
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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 Aug 7;255:109420. doi: 10.1016/j.thromres.2025.109420. Online ahead of print.

Reference Type DERIVED
PMID: 41027123 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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NL87503.058.24

Identifier Type: -

Identifier Source: org_study_id

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