Clinical trial NCT06833827: 'Thrombectomy in High-Risk Pulmonary Embolism - Device Versus Thrombolysis Netherlands': TORPEDO-NL
Official title: 'Thrombectomy in High-Risk Pulmonary Embolism - Device Versus Thrombolysis Netherlands': TORPEDO-NL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pulmonary Embolism Acute
Keywords: Acute Pulmonary Embolism
Full dose systemic thrombolysis
Catheter-directed thrombectomy
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Heart Foundation
name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Zorginstituut Nederland: The Health Care Insurance Board
First posted: 2025-02-19
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: The composite incidence of the binary endpoints of all-cause mortality, treatment failure, major bleeding and all-cause stroke at day 30.
timeFrame: Day 30
Secondary outcomes:
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a better survival.
timeFrame: Day 7 and day 30
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower incidence of treatment failure.
timeFrame: Day 7 and day 30
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower incidence of all-cause mortality.
timeFrame: Day 7, day 30 and day 90
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower incidence of all-cause stroke.
timeFrame: Day 7 and day 30
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower composite incidence of the binary endpoints of the primary outcome at day 7.
timeFrame: Day 7
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a better Desirability of Outcome Ranking (DOOR).
timeFrame: Day 7
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower incidence of BARC3b and BARC3c bleeding.
timeFrame: Day 7 and day 30
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower incidence of ISTH major and non-major clinically relevant bleeding.
timeFrame: Day 7 and day 30
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower level of oxygen supplementation.
timeFrame: 48 hours
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with shorter length of stay (days) at the ICU (Intensive Care Unit) and in hospital.
timeFrame: Up to 1 year
measure: To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with better patient-relevant outcomes such as Quality of life (QoL), functional recovery and symptom burden.
timeFrame: Day 7 and after 3, 6, 9 and 12 months
measure: Cost-effectiveness analysis after a time horizon of one year and budget impact analysis
timeFrame: 1 Year
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
state: Zuid-holland
Study officials:
affiliation: Leiden University Medical Center
name: F. A. Klok, Prof. MD. PhD.
role: PRINCIPAL_INVESTIGATOR
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