'Thrombectomy in High-Risk Pulmonary Embolism - Device Versus Thrombolysis Netherlands': TORPEDO-NL
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 111
- 试验地点
- 1
- 主要终点
- The composite incidence of the binary endpoints of all-cause mortality, treatment failure, major bleeding and all-cause stroke at day 30.
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •"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.
- •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.
研究组 & 干预措施
Catheter-directed thrombectomy (CDT)
Patients in the intervention group will receive Catheter-directed thrombectomy (CDT).
干预措施: Catheter-directed thrombectomy (CDT) (Device)
Systemic Thrombolysis
Patients in the control group will receive full-dose systemic thrombolysis.
干预措施: thrombolysis therapy (Drug)
结局指标
主要结局
The composite incidence of the binary endpoints of all-cause mortality, treatment failure, major bleeding and all-cause stroke at day 30.
时间窗: Day 30
This outcome will be assessed using patient records or information provided by the treating physician. A detailed description of treatment failure is provided in outcome 3 of the secondary outcomes. Major bleeding is defined as Bleeding Academic Research Consortium (BARC)3b and BARC3c bleeding (=intracranial haemorrhage). Ischemic stroke is defined as any stroke (National Institutes of Health Stroke Scale ≥1). Unit of measure: incidence (number and percentage).
次要结局
- To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a better survival.(Day 7 and day 30)
- To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower incidence of treatment failure.(Day 7 and day 30)
- 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.(Day 7, day 30 and day 90)
- 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.(Day 7 and day 30)
- 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.(Day 7)
- 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).(Day 7)
- 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.(Day 7 and day 30)
- 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.(Day 7 and day 30)
- To evaluate, after randomization, whether CDT in high-risk PE patients relative to systemic thrombolysis is associated with a lower level of oxygen supplementation.(48 hours)
- 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.(Up to 1 year)
- 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.(Day 7 and after 3, 6, 9 and 12 months)
- Cost-effectiveness analysis after a time horizon of one year and budget impact analysis(1 Year)
研究者
Erik Klok
Clinical Professsor
Leiden University Medical Center