Percutaneous Embolectomy, Low Dose Thrombolysis or Heparin for Intermediate High Risk Pulmonary Embolism (STRATIFY II)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 210
- 试验地点
- 5
- 主要终点
- Thrombus burdon reduction (intervention vs. heparin)
研究概览
简要总结
The STRATIFY II trial investigates the efficacy of three different approaches to reducing thrombus burdon in patients with acute intermediate high-risk pulmonary embolism: percutaneous embolectomy (the AlphaVAC(R), AngioDynamics or the Flow Triever® system, INARI medical), Low intravenous thrombolysis (Alteplase 10 mg) and heparin with the option to perform full-dose thrombolysis. As a co-primary secondary end point the trial assess the incremental efficacy of the embolectomy vs the catheter based low dose thrombolysis approach.
Thus the two main hypothesis being tested are:
- Thrombus burden reduction after 48-96 h is increased with a catheter based (embolectomy or low-dose alteplase) compared to the a heparin with optional high dose thrombolysis approach (1st co-primary outcome)
- Thrombus burden reduction after 48-96 h is increased with percutaneous embolectomy compared to low-dose alteplase (2nd co-primary outcome)
详细描述
Background: Intermediate-high risk pulmonary embolism (PE) is associated with a significant risk of death or hemodynamic deterioration. The optimal treatment strategy should balance efficacy in reducing thrombus burden and hemodynamic compromise with risk of complications, in particular bleeding. Previous studies have investigated conventional high-dose, short term thrombolysis by recombinant tissue Plasminogen Activator (rtPA), finding a reduction in risk hemodynamic deterioration, but not in mortality, and a substantial increase in significant bleeding complications.
Percutaneous catheter-based techniques of embolectomy or low dose thrombolysis may offer lower risk of complication while still being efficacious. A clinical equipoise remains as data from RCTs of reasonable size remain to be published.
The current trial addresses this paucity of data by randomizing patients to one of three treatment modalities:
Design: Regional collaborative, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE and no absolute contraindications to thrombolysis Intervention: 1:1:1 randomization (stratified for index hospital) to
• Percutaneous Embolectomy plus unfractionated heparin (UFH) or low molecular weight heparin (LMWH) within 12 hours of randomization.
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
- •Age ≥ 18 years
- •Intermediate high-risk PE according to ESC criteria
- •Class II risk assessed by the Pulmonary Embolism Severity Index (1).
- •Thrombus visible in main, lobar or segmental pulmonary arteries on CT angiography
- •14 days of symptoms or less, with significant worsening of symptoms within 7 days
排除标准
- •Altered mental state (GCS < 14)
- •No qualifying CT angiography performed (> 24 hour since CT angiography)
- •Women of childbearing potential, unless negative HCG test is present.
- •Thrombolysis for PE within 14 days of randomization
- •Thrombus passing through patent Foramen Ovale (risk of paradoxical embolism)
- •Ongoing oral anticoagulation therapy (heparins, aspirin, antiplatelet therapy and NOAC allowed)
- •Comorbidity making 6 months survival unlikely.
- •Absolute contraindications for thrombolysis:
- •History of haemorrhagic stroke or stroke of unknown origin
- •Ischaemic stroke in previous 6 months
- •Central nervous system neoplasm
- •Major trauma, surgery, or head injury in previous 3 weeks
- •Bleeding diathesis - Active bleeding
研究组 & 干预措施
Unfractionated Heparin / Low molecular heparin and thrombolysis if needed
Standard medical Therapy for intermediate-high risk pulmonary embolism
干预措施: Heparin (Drug)
Percutaneous Thrombectomy
Percutaneous Embolectomy using the AlphaVac, Angiodynamics or the Inari (R) Flowtriever thrombectomy system (R) and heparin
干预措施: Percutaneous Embolectomy (Device)
Low dose thrombolysis
10 mg af alteplase intravenously over 6 hours total and heparin
干预措施: Ultrasound assisted Thrombolysis (Device)
结局指标
主要结局
Thrombus burdon reduction (intervention vs. heparin)
时间窗: To end of inclusion + 96 hours
Reduction in modified Miller score (score of thrombus involvement and segmental flow) comparing percutaneous treated groups (embolectomy and low dose thrombolysis) to heparin/LMWH alone group, p\<0.01 (n=140 vs. n=70)
Thrombus burdon reduction (USAT vs. embolektomy)
时间窗: To end of inclusion + 96 hours
Reduction in modified Miller score (score of thrombus involvement and segmental flow) comparing percutaneous embolectomy and low dose thrombolysis, p\<0.04 (n=70 vs n=70)
次要结局
- Bleeding complications (major and minor bleeding complication according the TIMI classification)(3 months)
- Dyspnea index (Visual analog scale) after 48-96 hours and after 3 months(96 hours and 3 months)
- Rate of further interventions for pulmonary embolism during index admission(3 months)
- Mortality in the three groups (log-rank), and hazard ratio in multivariable analysis using the UFH/LMWH as reference. Inclusion date of last patient's 3 month follow-up defines last day of follow-up(1 year on avarage, at least 3 months)
- 6MWD at 3 months comparing the three groups(3 months)
- Quality of life at 3 months follow-up comparing the three groups (PEmbQoL)(3 months)
- Duration of index admission, including hospital based rehabilitation(3 months)
- Incidence of TR gradient > 40 mmHg at 3 months follow-up echocardiography(through study completion, an average of 1 year)
研究者
Jesper Kjaergaard
Consultant MD PhD DMSc
Rigshospitalet, Denmark