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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.

調査の概要

状態

まだ募集していません

詳細な説明

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.

研究の種類

介入

入学 (推定)

400

段階

  • フェーズ 4

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:ランダム化
  • 介入モデル:並列代入
  • マスキング:独身

武器と介入

参加者グループ / アーム
介入・治療
実験的: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
他の名前:
  • Reduced-dose systemic thrombolysis, Low-dose alteplase, tPA
アクティブコンパレータ: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.
他の名前:
  • Full-dose systemic thrombolysis, Standard-dose alteplase, tPA

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Incidence of composite efficacy endpoint
時間枠: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
時間枠: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

二次結果の測定

結果測定
メジャーの説明
時間枠
All-cause mortality
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠:Within 7 days after randomization
Incidence of initiation of invasive or non-invasive mechanical ventilation.
Within 7 days after randomization
Win ratio for efficacy
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠:Within 30 days after randomization
Length of hospital stay.
Within 30 days after randomization
Major bleeding
時間枠: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
時間枠: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
時間枠:Within 7 days after randomization
Incidence of intracerebral bleeding.
Within 7 days after randomization

その他の成果指標

結果測定
メジャーの説明
時間枠
All-cause mortality at 12 months
時間枠:At 12 months after randomization
Incidence of death from any cause.
At 12 months after randomization
At 12 months after randomization
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠:At 12 months after randomization
Incidence of chronic thromboembolic pulmonary hypertension.
At 12 months after randomization
Health care resource utilization
時間枠:During 12 months after randomization
Cost of health care resource utilization during the 12-month follow-up period.
During 12 months after randomization

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

捜査官

  • 主任研究者:Kristina Svennerholm、Sahlgrenska University Hospital / University of Gothenburg

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年12月1日

一次修了 (推定)

2030年1月31日

研究の完了 (推定)

2031年1月31日

試験登録日

最初に提出

2026年9月2日

QC基準を満たした最初の提出物

2026年9月10日

最初の投稿 (実際)

2026年9月14日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月17日

QC基準を満たした最後の更新が送信されました

2026年9月14日

最終確認日

2026年9月1日

詳しくは

本研究に関する用語

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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 共有時間枠

After publication of the trial results.

IPD 共有アクセス基準

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

IPD 共有サポート情報タイプ

  • STUDY_PROTOCOL
  • SAP

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