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Reduced-Dose Versus Full-Dose Alteplase for High-Risk Pulmonary Embolism (REDSTEM)

2026年9月14日 更新者:Kristina Svennerholm、Sahlgrenska University Hospital

Reduced-Dose Versus Full-Dose Systemic Thrombolysis for High-Risk Pulmonary Embolism: A Multicentre, Randomised, Open-Label, Blinded-Endpoint Trial

High-risk pulmonary embolism is a life-threatening condition requiring immediate reperfusion therapy. Full-dose systemic thrombolysis is recommended as first-line treatment, but its use is limited by the risk of major bleeding, including intracranial hemorrhage. Reduced-dose systemic thrombolysis may reduce bleeding while maintaining clinical efficacy, but this strategy has not been adequately evaluated in patients with high-risk pulmonary embolism.

REDSTEM is an international, multicenter, randomized, adaptive, open-label, blinded-endpoint phase 4 trial comparing reduced-dose alteplase with standard full-dose alteplase in adults with acute high-risk pulmonary embolism. The trial will assess whether reduced-dose alteplase preserves early clinical efficacy while reducing severe clinically significant bleeding. Participants will be followed for up to 12 months.

研究概览

详细说明

Systemic thrombolysis is recommended as first-line reperfusion therapy for high-risk pulmonary embolism. However, bleeding complications limit its use in clinical practice and contribute to undertreatment of eligible patients. Existing evidence from small randomized trials, observational studies, and meta-analyses suggests that lower-dose thrombolysis may improve safety while maintaining efficacy, but previous studies have included mixed-risk pulmonary embolism populations and only a limited number of patients with high-risk pulmonary embolism.

REDSTEM was designed to evaluate whether a reduced-dose alteplase strategy can provide a more favorable balance between efficacy and safety compared with standard full-dose alteplase in patients with high-risk pulmonary embolism. The study uses randomized treatment allocation, blinded endpoint adjudication, independent safety monitoring, and an adaptive design allowing sample-size re-estimation if required.

The trial includes early clinical assessments during the acute phase and follow-up through 12 months to evaluate clinical outcomes, safety, functional recovery, quality of life, and health care resource utilization.

研究类型

介入性

注册 (估计的)

400

阶段

  • 第四阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

      • Copenhagen、丹麦
        • Rigshospitalet
        • 接触:
          • Jesper Kjaergaard, MD, PhD
      • Bergen、挪威、5021
        • Haukeland University Hospital
        • 接触:
          • Lasse Melvear Gii, MD, PhD
      • Drammen、挪威、3004
        • Drammen Hospital
        • 接触:
          • Jonas Pivoriunas, MD, PhD
      • Grålum、挪威、1714
        • Ostfold Hisptal
        • 接触:
          • Hans Joakim Myklebust-Hansen, MD
      • Lörenskog、挪威、1478
        • Akershus University Hospital
        • 接触:
          • Hamza Nahoui, MD
      • Oslo、挪威、0450
        • Oslo University Hospital, Ullevål
        • 接触:
          • Mari Asphjell Björnaas, MD, PhD
      • Stavanger、挪威、4021
        • Stavanger University Hospital
        • 接触:
          • Trond Johan Cooper, MD
      • Falun、瑞典
        • Falun Hospital
        • 接触:
          • Jessica Silfverberg, MD
      • Gothenburg、瑞典
        • Sahlgrenska University Hospital/Östra
        • 接触:
          • Katarina Glise Sandblad, MD, PhD
      • Jönköping、瑞典
        • Ryhov County Hospital
        • 接触:
          • Antheia Kissopoulou, MD, PhD
      • Lund、瑞典
        • Skåne University Hospital, Lund
        • 接触:
          • Marcus Ohlsson, MD
      • Malmö、瑞典
        • Skåne University Hospital, Malmö
        • 接触:
          • Marcus Ohlsson, MD, PhD
      • Mölndal、瑞典
        • Sahlgrenska University Hospital/Mölndal
        • 接触:
          • Louise Martinell, MD, PhD
      • Norrtälje、瑞典
        • Norrtälje Hospital
        • 接触:
          • Sune Forsberg, MD, PhD
      • Skövde、瑞典
        • Skaraborgs Hospital Skövde
        • 接触:
          • Freyr Einarsson, MD
        • 接触:
          • Erik Ullemark, MD
      • Stockholm、瑞典
        • Danderyd Hospital
        • 接触:
          • Nina Olausson, MD, PhD
      • Stockholm、瑞典
        • Karolinska University Hospital, Solna
        • 接触:
          • Therese Djärv, MD, PhD
      • Stockholm、瑞典
        • Karolinska University Hospital, Huddinge
        • 接触:
          • Therese Djärv, MD, PhD
      • Stockholm、瑞典
        • Capio S:t Göran's Hospital
        • 接触:
          • Rickard Markgren, MD, PhD
      • Stockholm、瑞典
        • Södersjukhuset, Stockholm South General Hospital
        • 接触:
          • Jacob Hollenberg, MD, PhD
      • Umeå、瑞典
        • University Hospital of Umeå
        • 接触:
          • Johanna Pennlert, MD, PhD
      • Uppsala、瑞典
        • Uppsala University Hospital
        • 接触:
          • Sofia Vikman, MD, PhD
    • Västra Götaland County

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. Participant aged 18 years or older.
  2. Acute pulmonary embolism verified by computed tomography pulmonary angiography or pulmonary angiography. In hemodynamically unstable participants unable to undergo immediate imaging, presumed pulmonary embolism may be diagnosed based on bedside echocardiographic findings consistent with acute right ventricular pressure overload and high clinical suspicion of pulmonary embolism, provided that alternative causes of hemodynamic instability have been reasonably excluded. In such cases, the treating clinician must have independently decided to initiate thrombolytic therapy irrespective of study participation, and confirmatory imaging demonstrating pulmonary embolism must be performed as soon as clinically feasible.
  3. High risk for early death, defined by at least one of the following:

    1. High-risk pulmonary embolism according to European Society of Cardiology criteria:

      • Cardiac arrest with return of spontaneous circulation;
      • Obstructive shock, defined as systolic blood pressure <90 mmHg or use of vasopressors to maintain systolic blood pressure ≥90 mmHg despite adequate filling status, together with end-organ hypoperfusion such as elevated serum lactate >2 mmol/L, altered mental status, or cold clammy skin;
      • Persistent hypotension, defined as systolic blood pressure <90 mmHg or a drop in systolic blood pressure ≥40 mmHg for longer than 15 minutes, not caused by new-onset arrhythmia, hypovolemia, or sepsis.
    2. Abnormal right ventricular function on echocardiography or computed tomography pulmonary angiography, defined as right ventricular/left ventricular ratio ≥1.0, and elevated cardiac troponin above the local upper reference limit, and acute respiratory failure not primarily caused by underlying lung disease, defined as requiring facemask oxygen supplementation ≥12 L/min, high-flow nasal oxygen, or non-invasive ventilation with FiO2 ≥60% to reach oxygen saturation ≥94%.
  4. Female participants of childbearing potential must have a negative urine or serum pregnancy test.

Exclusion Criteria:

  1. Catastrophic pulmonary embolism, defined as ongoing cardiac arrest and/or need for extracorporeal cardiopulmonary resuscitation and/or immediate VA-ECMO as judged by the treating physicians.
  2. Known hypersensitivity to alteplase or any of its excipients.
  3. Contraindication to systemic thrombolysis with one or more of the following:

    • History of hemorrhagic stroke;
    • Ischemic stroke within the previous 6 months;
    • Central nervous system neoplasm;
    • Major trauma, major surgery, or major head injury within the previous 3 weeks;
    • Active life-threatening bleeding, bleeding into a critical organ or area, or known severe bleeding diathesis;
    • Chronic use of full-dose oral or parenteral anticoagulation before presentation.
  4. The participant has already received reperfusion treatment for the index pulmonary embolism before randomization, including systemic thrombolysis, surgical embolectomy, or catheter-directed intervention.
  5. Pregnancy.
  6. Current participation in another study that would interfere with participation in this trial.
  7. Any other condition that would put the participant at unacceptable risk from the trial interventions as judged by the treating clinician.
  8. In countries where required by national regulations: lack of affiliation to a social security system or equivalent health insurance coverage.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:单身的

武器和干预

参与者组/臂
干预/治疗
实验性的:Reduced-Dose Alteplase
Participants randomized to reduced-dose systemic thrombolysis will receive alteplase 0.6 mg/kg body weight, up to a maximum dose of 50 mg, administered intravenously over 15 minutes.
Alteplase 0.6 mg/kg body weight, maximum 50 mg, administered as an intravenous infusion over 15 minutes
其他名称:
  • Reduced-dose systemic thrombolysis, Low-dose alteplase, tPA
有源比较器:Full-Dose Alteplase
Participants randomized to standard full-dose systemic thrombolysis will receive alteplase 1.5 mg/kg body weight, up to a maximum dose of 100 mg, administered as a 10 mg intravenous bolus over 1 to 2 minutes followed by a 90 mg intravenous infusion over 2 hours.
Alteplase 1.5 mg/kg body weight, maximum 100 mg, administered as a 10 mg intravenous bolus over 1 to 2 minutes followed by 90 mg as an intravenous infusion over 2 hours.
其他名称:
  • Full-dose systemic thrombolysis, Standard-dose alteplase, tPA

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Incidence of composite efficacy endpoint
大体时间:Within 7 days after randomization
Incidence of a composite endpoint comprising all-cause mortality within 7 days, cardiopulmonary resuscitation and/or veno-arterial extracorporeal membrane oxygenation within 7 days, recurrent pulmonary embolism within 7 days, clinical deterioration within 24 hours, and lack of clinical improvement at 6 hours.
Within 7 days after randomization
Key secondary endpoint - Incidence of severe clinically significant bleeding
大体时间:Within 7 days after randomization
Incidence of severe clinically significant bleeding, defined as major bleeding according to International Society on Thrombosis and Haemostasis criteria or bleeding requiring urgent medical intervention.
Within 7 days after randomization

次要结果测量

结果测量
措施说明
大体时间
All-cause mortality
大体时间:At 7 days and 30 days after randomization
Incidence of death from any cause.
At 7 days and 30 days after randomization
Pulmonary embolism-related mortality
大体时间:At 7 days and 30 days after randomization
Incidence of pulmonary embolism-related death.
At 7 days and 30 days after randomization
Cardiopulmonary resuscitation and/or VA-ECMO
大体时间:Within 7 days after randomization
Incidence of cardiopulmonary resuscitation and/or veno-arterial extracorporeal membrane oxygenation.
Within 7 days after randomization
Incidence of clinical deterioration
大体时间:Within 24 hours after randomization
Incidence of life-threatening hemodynamic or respiratory decline requiring cardiopulmonary resuscitation, endotracheal intubation, or VA-ECMO, or an increase in SCAI SHOCK stage after investigational medicinal product administration.
Within 24 hours after randomization
Lack of clinical improvement assessed by SCAI SHOCK stage and oxygen requirement
大体时间:At 6 hours after randomization
Incidence of unchanged SCAI SHOCK stage or unchanged or rising fraction of inspired oxygen required to maintain oxygen saturation of at least 94%.
At 6 hours after randomization
Time to clinical stabilization based on predefined hemodynamic and respiratory criteria
大体时间:From randomization until clinical stabilization, assessed up to 7 days after randomization
Time from randomization to the time point at which predefined hemodynamic or respiratory stabilization criteria have been continuously fulfilled for at least 30 minutes
From randomization until clinical stabilization, assessed up to 7 days after randomization
Incidence of recurrent pulmonary embolism
大体时间:At 7 days and 30 days after randomization
Incidence of objectively confirmed recurrent pulmonary embolism.
At 7 days and 30 days after randomization
Initiation of invasive or non-invasive mechanical ventilation
大体时间:Within 7 days after randomization
Incidence of initiation of invasive or non-invasive mechanical ventilation.
Within 7 days after randomization
Win ratio for efficacy
大体时间:Within 7 days after randomization
Win ratio based on all-cause mortality, cardiopulmonary resuscitation and/or VA-ECMO, clinical deterioration, lack of clinical improvement, recurrent pulmonary embolism, and time to clinical stabilization.
Within 7 days after randomization
Net clinical benefit
大体时间:Within 7 days after randomization
Composite net clinical benefit including severe clinically significant bleeding, all-cause mortality, cardiopulmonary resuscitation and/or VA-ECMO, recurrent pulmonary embolism, clinical deterioration, and lack of clinical improvement.
Within 7 days after randomization
Rescue treatment
大体时间:Before clinical stabilization, up to 7 days after randomization
Need for rescue treatment, defined as additional alteplase, catheter-directed intervention, surgical embolectomy, or VA-ECMO before stabilization.
Before clinical stabilization, up to 7 days after randomization
ICU or high-dependency unit length of stay in days
大体时间:Within 30 days after randomization
Length of stay in intensive care unit and/or high-dependency unit.
Within 30 days after randomization
Hospital length of stay
大体时间:Within 30 days after randomization
Length of hospital stay.
Within 30 days after randomization
Major bleeding
大体时间:At 48 hours, 7 days, and 30 days after randomization
Incidence of major bleeding according to International Society on Thrombosis and Haemostasis criteria.
At 48 hours, 7 days, and 30 days after randomization
Bleeding requiring urgent medical intervention
大体时间:At 48 hours, 7 days, and 30 days after randomization
Incidence of severe bleeding requiring urgent medical intervention.
At 48 hours, 7 days, and 30 days after randomization
Intracerebral bleeding
大体时间:Within 7 days after randomization
Incidence of intracerebral bleeding.
Within 7 days after randomization

其他结果措施

结果测量
措施说明
大体时间
All-cause mortality at 12 months
大体时间:At 12 months after randomization
Incidence of death from any cause.
At 12 months after randomization
At 12 months after randomization
大体时间:At 12 months after randomization
Incidence of objectively confirmed recurrent pulmonary embolism.
At 12 months after randomization
Persistent dyspnea assessed using the modified Medical Research Council scale
大体时间:At 3 months and 12 months after randomization
Persistent dyspnea assessed using the modified Medical Research Council scale.
At 3 months and 12 months after randomization
Functional status assessed using the Post-VTE Functional Status Scale
大体时间:At 3 months and 12 months after randomization
Functional status assessed using the post-VTE functional status (PVFS) scale. Scores range from 0 to 4, where 0 indicates no functional limitations and 4 indicates severe functional limitations. Higher scores indicate worse functional status. Death before the scheduled assessment is recorded as grade D.
At 3 months and 12 months after randomization
Exercise tolerance assessed using the 6-minute walk test
大体时间:At 3 months and 12 months after randomization
Exercise tolerance assessed using the 6-minute walk test, reported as distance walked in meters. A greater distance indicates better exercise tolerance.
At 3 months and 12 months after randomization
Persistent right ventricular dysfunction assessed by echocardiography
大体时间:At 3 months and/or 12 months after randomization
Persistent right ventricular dysfunction according to echocardiography report, when performed as clinically indicated.
At 3 months and/or 12 months after randomization
Pulmonary embolism-specific quality of life assessed using the PEmb-QoL questionnaire
大体时间:At 3 months and 12 months after randomization
Pulmonary embolism-specific health-related quality of life assessed using the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire. The PEmb-QoL summary score ranges from 0 to 100, with higher scores indicating worse health-related quality of life.
At 3 months and 12 months after randomization
Health-related quality of life assessed using EQ-5D-5L
大体时间:At 3 months and 12 months after randomization
Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument.
At 3 months and 12 months after randomization
Chronic thromboembolic pulmonary hypertension
大体时间:At 12 months after randomization
Incidence of chronic thromboembolic pulmonary hypertension.
At 12 months after randomization
Health care resource utilization
大体时间:During 12 months after randomization
Cost of health care resource utilization during the 12-month follow-up period.
During 12 months after randomization

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Kristina Svennerholm、Sahlgrenska University Hospital / University of Gothenburg

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年12月1日

初级完成 (估计的)

2030年1月31日

研究完成 (估计的)

2031年1月31日

研究注册日期

首次提交

2026年9月2日

首先提交符合 QC 标准的

2026年9月10日

首次发布 (实际的)

2026年9月14日

研究记录更新

最后更新发布 (实际的)

2026年9月17日

上次提交的符合 QC 标准的更新

2026年9月14日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

是的

IPD 计划说明

De-identified individual participant data underlying the published results may be shared upon reasonable request after publication. Access will require approval by the sponsor and principal investigator, a scientifically sound proposal, scientific collaboration with the trial investigators, compliance with applicable ethical, regulatory, data protection, and consent requirements, and a signed data sharing agreement.

IPD 共享时间框架

After publication of the trial results.

IPD 共享访问标准

Reasonable request, subject to approval by the sponsor and principal investigator and applicable legal, ethical, and data protection requirements.

IPD 共享支持信息类型

  • 研究方案
  • 树液

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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