RecruitingNot ApplicableNCT06833827

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

Sponsor

Leiden University Medical Center

Enrollment

111 participants

Start Date

Feb 1, 2025

Study Type

INTERVENTIONAL

Conditions

Pulmonary Embolism Acute

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

Min Age: 18 Years

Inclusion Criteria7

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.
High risk for mortality, i.e.
post cardiac arrest (after temporary need for cardiopulmonary resuscitation), OR
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
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
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.
CDT available and technically feasible so as to allow for a randomization-to-needle time of 60 minutes or less.

Exclusion Criteria20

"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)
Glascow Coma Scale \<8 following resuscitation for cardiac arrest
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.
A known "do not admit to the ICU" or "do not resuscitate" directive
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
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
Thrombus in transit through a patent foramen ovale.
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.
Known hypersensitivity to systemic thrombolysis, heparin, or to any of the excipients
If, in the Investigator's opinion, or after consultation with the local PERT-team or EC-members, the patient is not appropriate for thrombectomy
Chronic use of full-dose oral or parenteral anticoagulation before presentation.
Pregnancy
Current participation in another study that would interfere with participation in this study
Previous enrolment in this study
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.

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Interventions

DEVICECatheter-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.

DRUGthrombolysis 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.