Low Dose Thrombolysis, Ultrasound Assisted Thrombolysis or Heparin for Intermediate High Risk Pulmonary Embolism
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 210
- 试验地点
- 4
- 主要终点
- Reduction in Miller score comparing low dose thrombolysis and heparin alone groups
研究概览
简要总结
Open label clinical randomized trial comparing three strategies for managing acute intermediate-high risk pulmonary embolism
详细描述
Trial acronym: STRATIFY 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 (rtPA), finding a reduction in risk hemodynamic deterioration, but no reduction in mortality and a substantial increase in significant bleeding complications.
Catheter based techniques and low dose thrombolysis may offer lower risk of complication with reasonable efficacy. Such studies have not been performed in RCTs with a reasonable sample size, and no study have compared low dose intravenous thrombolysis and catheter based techniques.
The current trial addresses this paucity of data by randomizing patients to one of three treatment modalities:
Intervention: 1:1:1 randomization, stratified for site to
- UltraSound Assisted Thrombolysis (USAT) with low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus unfractionated heparin (UFH) or low molecular weight heparin (LMWH) within 12 hours of randomization
- Intravenous low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus UFH or low molecular weight heparin (LMWH).
- UFH or low molecular weight heparin (LMWH) only (with option for conventional thrombolysis according to local protocols for hemodynamic deterioration) Design: Regional collaborative, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE with no absolute contraindications to thrombolysis
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
- Single (Outcomes Assessor)
盲法说明
Primary endpoint will be assessed by assessor blinded to the intervention
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
- •Informed consent for trial participation
- •Intermediate high-risk PE according to ESC criteria
- •Thrombus visible in main, lobar or segmental pulmonary arteries on CT angiography
- •14 days of symptoms or less
排除标准
- •Altered mental state (GCS < 14)
- •No qualifying CT angiography performed (> 24 hour since CT angiography)
- •Females of child bearing 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
- •Hemorrhagic stroke or stroke of unknown origin at any time
- •Ischemic stroke in the preceding 6 months
- •Central nervous system damage or neoplasms
- •Recent major trauma/surgery/head injury in the preceding 3 weeks
- •Gastrointestinal bleeding within the last month
- •Known bleeding risk
研究组 & 干预措施
USAT + low dose thrombolysis
UltraSound Assisted Thrombolysis (USAT) with low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus unfractionated heparin (UFH) or low molecular weight heparin (LMWH) within 12 hours of randomization
干预措施: Alteplase 20 Mg Powder for Solution for Injection Vial (Drug)
USAT + low dose thrombolysis
UltraSound Assisted Thrombolysis (USAT) with low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus unfractionated heparin (UFH) or low molecular weight heparin (LMWH) within 12 hours of randomization
干预措施: Ultrasound assisted Thrombolysis (Device)
Low dose thrombolysis
Intravenous low dose thrombolysis (20 mg of rtPA, Alteplase) over 6 hours plus UFH or low molecular weight heparin (LMWH).
干预措施: Alteplase 20 Mg Powder for Solution for Injection Vial (Drug)
结局指标
主要结局
Reduction in Miller score comparing low dose thrombolysis and heparin alone groups
时间窗: at 48 to 96 hours post randomization
Reduction in Miller Score and on follow-up (48-96 h) CT pulmonary Angiography comparing low-dose rtPA (±USAT) to UFH/LMWH group (p\<0.01, N=210)
Reduction i Miller score comparing low dose thrombolysis by iv and by USATgroups
时间窗: at 48 to 96 hours post randomization
reduction in Miller Score and on follow-up (48-96 h) CT pulmonary Angiography comparing low-dose rtPA by USAT to iv, p\<0.04, N=140)
次要结局
- Incidence of bleeding complications(Until hospital discharge, on average 1 week)
- 6 minute walk distance af follow-up(3 months follow-up)
- Health related Quality of Life (PEmb-QoL)(3 months follow-up)
- Health related Quality of Life (EQ-5D-5L)(3 months follow-up)
- Dyspnea index by visual analogue scale(End of study, expected to be 5 years)
- Length of stay of index admission(End of study, expected to be 5 years)
- Change in oxygen supplement (FiO2)(at 48 to 96 hours post randomization)
- Mortality rate(End of study, expected to be 5 years)
- Incidence of Pulmonary Hypertension(3 months follow-up)
研究者
Jesper Kjaergaard
Sponsor, Primary investigator
Rigshospitalet, Denmark