Kjærgaard Jesper, Carlsen Jørn, Sonne-Holm Emilie, Wiberg Sebastian, Holmvang Lene, Lassen Jens Flensted, Sørensen Rikke, Høfsten Dan, Ulriksen Peter Sommer, Jawad Samir, Palm Pernille, Thune Jens Jakob, Hassager Christian, Kristiansen Ole P, Eskesen Kristian, Fanø Søren, Bang Lia E
Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Cardiothoracic Anesthesiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Danmark.
Trials. 2024 Dec 28;25(1):853. doi: 10.1186/s13063-024-08688-4.
Intermediate-high risk pulmonary embolism (PE) carries a significant risk of hemodynamic deterioration or death. Treatment should balance efficacy in reducing clot burden with the risk of complications, particularly bleeding. Previous studies on high-dose, short-term thrombolysis with alteplase (rtPA) showed a reduced risk of hemodynamic deterioration but no change in mortality and increased bleeding complications. Catheter-based techniques, including ultrasound-assisted thrombolysis (USAT), and low-dose thrombolysis may offer reasonable efficacy with lower risk. However, studies comparing these methods have been few. This trial aims to address this gap by randomizing patients to three treatment modalities.
Multicenter, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE, excluding those with absolute contraindications to thrombolysis. Patients are eligible for inclusion if they are > 18 years of age, have had symptoms < 14 days, and are able to give informed consent. Patients are allocated 1:1:1 into three treatment strategies: (1) unfractionated heparin (UFH)/low molecular weight heparin (LMWH), (2) UFH/LMWH + 20 mg rtPA/6 h intravenously (IV), or (3) UFH + 20 mg rtPA/6 h via USAT. Co-primary outcomes include reduction in clot burden as assessed by refined Miller score from pre-treatment to follow-up (48-96 h) computed tomography pulmonary angiogram (CTPA) comparing low-dose rtPA (± USAT) groups to UFH/LMWH group (p < 0.01, N = 210) and reduction in refined Miller score on follow-up CT angiography comparing low-dose rtPA by USAT to intravenous rtPA, p < 0.04, N = 140). Secondary outcomes comprise bleeding complications, duration of index admission, FiO, blood pressure, respiratory and heart rate at the time of follow-up CT angiography, mortality in the three groups, incidence of tricuspid regurgitation pressure gradient < 40 mmHg at 3 months follow-up echocardiography, 6-min walk test at 3 months comparing the three groups, and health-related quality of life at 3 months follow-up comparing the three groups.
We hypothesize that in patients with intermediate-high risk PE (1) administration of 20 mg rtPA leads to a greater reduction in clot burden compared to heparins and (2) administration of 20 mg rtPA via USAT results in a greater reduction in clot burden compared to 20 mg rtPA intravenous.
ClinicalTrials.gov NCT04088292. Registered in September 2019 (retrospectively registered).
中高危肺栓塞（PE）具有血流动力学恶化或死亡的重大风险。治疗应在降低血栓负荷的疗效与并发症风险（尤其是出血风险）之间取得平衡。先前关于大剂量、短期使用阿替普酶（rtPA）溶栓的研究表明，血流动力学恶化风险降低，但死亡率无变化，且出血并发症增加。基于导管的技术，包括超声辅助溶栓（USAT）和低剂量溶栓，可能在风险较低的情况下提供合理的疗效。然而，比较这些方法的研究较少。本试验旨在通过将患者随机分配至三种治疗方式来填补这一空白。
一项多中心随机试验，将210例急性中高危PE患者按1:1:1分配，排除有溶栓绝对禁忌证的患者。年龄>18岁、症状出现<14天且能够给予知情同意的患者符合纳入条件。患者按1:1:1分配至三种治疗策略：（1）普通肝素（UFH）/低分子肝素（LMWH），（2）UFH/LMWH + 20 mg rtPA静脉注射（IV）/6小时，或（3）UFH + 20 mg rtPA通过USAT/6小时。共同主要结局包括通过改良米勒评分评估的从治疗前到随访（48 - 96小时）计算机断层扫描肺动脉造影（CTPA）时血栓负荷的降低，比较低剂量rtPA（±USAT）组与UFH/LMWH组（p < 0.01，N = 210），以及在随访CT血管造影时比较经USAT的低剂量rtPA与静脉注射rtPA的改良米勒评分降低情况，p < 0.04，N = 140）。次要结局包括出血并发症、首次住院时间、随访CT血管造影时的FiO、血压、呼吸和心率、三组的死亡率、3个月随访超声心动图时三尖瓣反流压力梯度<40 mmHg的发生率、3个月时比较三组的6分钟步行试验，以及3个月随访时比较三组的健康相关生活质量。
我们假设，在中高危PE患者中，（1）与肝素相比，给予20 mg rtPA可使血栓负荷降低更多；（2）与静脉注射20 mg rtPA相比，通过USAT给予20 mg rtPA可使血栓负荷降低更多。
ClinicalTrials.gov NCT04088292。于2019年9月注册（追溯注册）。
