Reduced-Dose Thrombolysis in Intermediate-Risk Pulmonary Embolism With High-Risk Features (REDUCTION)
Reduced-Dose Thrombolysis in Intermediate-High Risk Pulmonary Embolism, a Multicenter, Randomized Controlled Trial
Alteplase, a recombinant tissue plasminogen activator (rt-PA), is commonly used for thrombolytic treatment in patients with high-risk acute pulmonary thromboembolism (PTE), whereas the role of thrombolysis in intermediate-risk PTE remains controversial. This multicenter, randomized controlled trial will compare the efficacy and safety of reduced-dose alteplase (25 mg administered intravenously over 2 hours) plus standard anticoagulation with standard anticoagulation alone in patients with intermediate-risk PTE who have high-risk features.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
In patients with intermediate-risk pulmonary embolism (PE), full-dose systemic thrombolysis has been associated with a reduction in the risk of hemodynamic decompensation but an increased risk of major and intracranial bleeding. Previous studies suggest that reduced-dose thrombolysis may improve right ventricular (RV) function while potentially reducing bleeding complications. However, evidence regarding the efficacy and safety of reduced-dose systemic thrombolysis in patients with intermediate risk PE and additional high-risk clinical features remains limited. This study aims to evaluate the efficacy and safety of reduced-dose thrombolytic therapy in this patient population.
The REDUCTION study is a multicenter, randomized, open-label, controlled trial with blinded endpoint assessment and long-term follow-up.
Eligible patients will be randomly assigned in a 1:1 ratio to receive reduced-dose alteplase combined with standard anticoagulation or standard anticoagulation alone. Randomization will be centrally managed and stratified by participating center.
Patients will receive:
- Reduced-dose alteplase group: Alteplase 25 mg administered by intravenous infusion over 2 hours, followed by standard anticoagulation with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) for at least 5 days.
- Standard anticoagulation group: Standard anticoagulation with LMWH or UFH for at least 5 days without thrombolytic therapy.
The primary objective is to assess the efficacy of reduced-dose alteplase in improving RV function at 48 hours, as measured by the change in the ratio of right ventricular to left ventricular end-diastolic diameters (RVED/LVED) on echocardiography.
The secondary objectives are to evaluate early changes in right ventricular function, clinical deterioration, PE-related mortality, recurrent PE, and bleeding complications. Long-term assessments will evaluate persistent dyspnea, functional status, persistent right ventricular dysfunction, and the occurrence of chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH)
Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Fase 3
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Changming Xiong, Prof.
- Numero di telefono: (+86)010-88396798
- Email: xiongcmfw@163.com
Luoghi di studio
-
-
-
Beijing, Cina, 100037
- Chinese Academy of Medical Sciences, Fuwai Hospital
-
Contatto:
- Changming Xiong, Prof.
- Numero di telefono: 010-88396798
- Email: xiongcmfw@163.com
-
-
Beijing Municipality
-
Beijing, Beijing Municipality, Cina, 100029
- China-Japan Friendship Hospital
-
Contatto:
- Zhenguo Zhai
- Numero di telefono: 010-84205566
- Email: zhaizhenguo2011@126.com
-
Beijing, Beijing Municipality, Cina, 100730
- Peking Union Medical College Hospital
-
Contatto:
- Juhong Shi, Prof.
- Numero di telefono: 010-69156114
- Email: shijh@pumch.cn
-
Beijing, Beijing Municipality, Cina, 100029
- Beijing Anzhen Hospital, Capital Medical University
-
Contatto:
- Jun Wan, Prof.
- Numero di telefono: 010-64412431
- Email: blueswan2013@yahoo.com
-
Beijing, Beijing Municipality, Cina, 100020
- Beijing ChaoYang Hospital.Capital Medical University
-
Contatto:
- Yuanhua Yang, Prof.
- Numero di telefono: 010-85231777
- Email: yyh1031@sina.com
-
-
Guangdong
-
Guangzhou, Guangdong, Cina, 510120
- Guangdong Provincial Hospital of Chinese Medicine
-
Contatto:
- Yinji Xu, Prof.
- Numero di telefono: 020-81887233
- Email: xuyinji@163.com
-
Guangzhou, Guangdong, Cina, 510120
- The First Affiliated Hospital of Guangzhou Medical University / Guangzhou Institute of Respiratory Health (National Clinical Research Center for Respiratory Disease)
-
Contatto:
- Nuofu Zhang, Prof.
- Numero di telefono: 020-83062114
- Email: nfzhanggird@163.com
-
Shenzhen, Guangdong, Cina, 518116
- Longgang Central Hospital of Shenzhen
-
Contatto:
- Siliang Xu, Prof.
- Numero di telefono: 0755-84806933
- Email: 420814562@qq.com
-
-
Hebei
-
Zhangjiakou, Hebei, Cina, 075000
- The First Affiliated Hospital of Hebei North University
-
Contatto:
- Baoli Xiang, Prof.
- Numero di telefono: 0313-8043555
- Email: 15530396731@163.com
-
-
Henan
-
Xinxiang, Henan, Cina, 453400
- HeNan Honliv Hospital
-
Contatto:
- Lei Yang, Prof.
- Numero di telefono: 0373-8882288
- Email: 61194255@qq.com
-
Zhengzhou, Henan, Cina, 450052
- The First Affiliated Hospital of Zhengzhou University
-
Contatto:
- Zhe Cheng, Prof.
- Numero di telefono: 0371-66913114
- Email: chengzhehi@126.com
-
Zhengzhou, Henan, Cina, 450003
- Henan Provincial People's Hospital
-
Contatto:
- Yong Qi, Prof.
- Numero di telefono: 0371-65580014
- Email: srmyy123@163.com
-
-
Hubei
-
Wuhan, Hubei, Cina, 430015
- Wuhan Sixth Hospital (Affiliated Hospital of Jianghan University)
-
Contatto:
- Fajiu Li, Prof.
- Numero di telefono: 027-82426502
- Email: 80670519@qq.com
-
-
Inner Mongolia
-
Baotou, Inner Mongolia, Cina, 014010
- Inner Mongolia Baogang Hospital
-
Contatto:
- Hongjun Tian, Prof.
- Numero di telefono: 0472-5992811
- Email: 1139717960@qq.com
-
Tongliao, Inner Mongolia, Cina, 028000
- NMG Keerqin District Hosp.
-
Contatto:
- Xili Wang, Prof.
- Numero di telefono: 0475-8232510
- Email: 861004223@qq.com
-
-
Jiangsu
-
Changzhou, Jiangsu, Cina, 213003
- The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University
-
Contatto:
- Qian Zhang, Prof.
- Numero di telefono: 0519-81099988
- Email: kezhang0601@163.com
-
Nanjing, Jiangsu, Cina, 210006
- Nanjing First Hospital
-
Contatto:
- He Xu, Prof.
- Numero di telefono: 025-52271000
- Email: hexunj@163.com
-
-
Liaoning
-
Shenyang, Liaoning, Cina, 110024
- Central Hospital Affiliated to Shenyang Medical College
-
Contatto:
- Shuyue Xia, Prof.
- Numero di telefono: 024-85715200
- Email: syx262@126.com
-
Shenyang, Liaoning, Cina, 110003
- General Hospital of Northern Theater Command
-
Contatto:
- Liang Shi, Prof.
- Numero di telefono: 024-28886666
- Email: 13309889463@163.com
-
-
Ningxia
-
Yinchuan, Ningxia, Cina, 750004
- Ningxia Medical University General Hospital
-
Contatto:
- Juan Chen, Prof.
- Numero di telefono: 0951-6744457
- Email: chenjuan7419@163.com
-
-
Shandong
-
Jinan, Shandong, Cina, 250021
- Shandong Provincial Hospital
-
Contatto:
- Ling Zhu, Prof.
- Numero di telefono: 0531-87938911
- Email: zhuling7103@163.com
-
Linyi, Shandong, Cina, 276000
- Linyi People's Hospital
-
Contatto:
- Le Kang, Prof.
- Numero di telefono: 0539-8616398
- Email: 593119267@qq.com
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, Cina, 200120
- Shanghai East Hospital, School of Medicine, Tongji University
-
Contatto:
- Yingqun Ji, Prof.
- Numero di telefono: 021-38804518
- Email: jiyingqun@163.com
-
-
Sichuan
-
Chengdu, Sichuan, Cina, 610041
- West China Hospital, Sichuan University
-
Contatto:
- Maojun Wang, Prof.
- Numero di telefono: 028-85422114
- Email: wmmyun@hotmail.com
-
-
Tianjin Municipality
-
Tianjin, Tianjin Municipality, Cina, 300052
- Tianjin Medical University General Hospital
-
Contatto:
- Lixia Dong, Prof.
- Numero di telefono: 022-96580
- Email: 18355193818@163.COM
-
Tianjin, Tianjin Municipality, Cina, 300222
- Tianjin Chest Hospital
-
Contatto:
- Songtao Gu
- Numero di telefono: 022-88185111
- Email: gusongtaodoctor@126.com
-
-
Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
-
Age 18 to 75 years
-
Objectively confirmed acute pulmonary thromboembolism (PTE) with symptom onset within 14 days, based on at least one of the following:
- Ventilation/perfusion lung scan showing at least one segmental or larger mismatched perfusion defect;
- Computed tomography pulmonary angiography (CTPA) or pulmonary angiography showing a filling defect or abrupt obstruction in a segmental or more proximal pulmonary artery.
-
Intermediate-high-risk PTE, with both of the following:
- Right ventricular dysfunction (RVD) on echocardiography or CTPA. Echocardiographic RVD is defined by at least one of the following:(1) right ventricular dilation with RV/LV end-diastolic diameter ratio >1.0; (2) reduced right ventricular free-wall motion; (3) increased tricuspid regurgitation velocity;(4) tricuspid annular plane systolic excursion <16 mm; (5) tricuspid annular systolic velocity (S') <9.5 cm/s. CTPA evidence of RVD is defined as right ventricular dilation with RV/LV end-diastolic diameter ratio >1.0.
- Cardiac injury or heart failure biomarker above the local upper limit of normal, including cardiac troponin, BNP, or NT-proBNP.
-
Elevated risk of early death/hemodynamic collapse, indicated by at least one of the following high-risk features: Systolic blood pressure ≤110 mmHg, Heart rate ≥100 beats/min, Oxygen saturation (SpO₂) <90% (respiratory rate >20 breaths/min or arterial partial pressure of oxygen [PaO₂] <60 mmHg).
-
Signed informed consent
Exclusion Criteria:
-
High-risk PTE with hemodynamic instability, including cardiac arrest, obstructive shock, or persistent hypotension defined as systolic blood pressure <90 mmHg or a decrease of ≥40 mmHg from baseline lasting at least 15 minutes, after excluding hypotension caused by new-onset arrhythmia, hypovolemia, or sepsis.
-
Intermediate-low-risk PTE, defined as hemodynamically stable PE with only one of the following findings: right ventricular dysfunction on imaging or elevated cardiac biomarkers.
-
Low-risk PTE, defined as hemodynamically stable PTE without right ventricular dysfunction and without elevated cardiac injury or heart failure biomarkers.
-
Any contraindication to systemic thrombolysis, including:
- Known hypersensitivity to alteplase, gentamicin, heparin, low-molecular-weight heparin, or any component of the study treatment;
- Active bleeding or high risk of bleeding;
- Known or suspected intracranial hemorrhage;
- Suspected subarachnoid hemorrhage or aneurysmal subarachnoid hemorrhage;
- Significant bleeding disorder within the previous 6 months;
- Known bleeding diathesis;
- Acute ischemic stroke or transient ischemic attack within the previous 6 months;
- Ophthalmic surgery within the previous 3 months, or abdominal, cardiac, thoracic, vascular, or orthopedic surgery or trauma within the previous 3 months;
- History of central nervous system disease or trauma, including tumor, aneurysm, head trauma, intracranial surgery, or spinal surgery;
- Platelet count <100 × 10^9/L;
- International normalized ratio (INR) >1.3;
- Current effective oral anticoagulant treatment;
- Traumatic cardiopulmonary resuscitation;
- Infective endocarditis or pericarditis;
- Acute pancreatitis;
- Noncompressible vascular puncture;
- Severe uncontrolled hypertension, with systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg;
- Any other condition considered by the investigator to confer a high bleeding risk;
- Severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varices, or active hepatitis;
- Gastrointestinal ulcer, esophageal varices, arterial aneurysm, or arteriovenous malformation within the previous 3 months;
- Tumor with bleeding tendency;
- Pregnancy or within 1 week postpartum;
- Diabetes with hemorrhagic retinopathy;
-
Body weight ≤40 kg.
-
Thrombolytic treatment within 30 days before randomization for the current episode of acute PE, including systemic or catheter-directed thrombolysis.
-
Catheter-directed mechanical thrombectomy or surgical pulmonary embolectomy before randomization for the current episode of acute PE.
-
Use of any direct oral anticoagulant within 30 days before randomization.
-
Current dual antiplatelet therapy.
-
Current participation in another interventional clinical trial.
-
Women of childbearing potential who are unwilling to use effective contraception or abstinence during the study.
-
Any other disease or condition that, in the investigator's judgment, would increase treatment risk.
-
Life expectancy <3 months or inability to complete 3-month follow-up.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Separare
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
|
Comparatore attivo: Reduced-Dose Alteplase and Standard Anticoagulation
Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) and reduced-dose alteplase [25 mg continuous intravenous infusion for 2 hours] |
Alteplase 25 mg will be administered by continuous intravenous infusion over 2 hours Standard anticoagulation will consist of LMWH or UFH administered according to current guideline recommendations for at least 5 days |
|
Comparatore attivo: Standard Anticoagulation
Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) |
Standard anticoagulation will consist of LMWH or UFH administered according to current guideline recommendations for at least 5 days |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Lasso di tempo: Between baseline and 48 hours
|
Between baseline and 48 hours
|
Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Change in the ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter (RVED/LVED) as measured by echocardiography
Lasso di tempo: Between baseline and 7 days
|
Between baseline and 7 days
|
|
|
Clinical Deterioration
Lasso di tempo: 7 days
|
7 days
|
|
|
PE-Related Death
Lasso di tempo: 7 days
|
Death caused by pulmonary embolism (PE) |
7 days
|
|
All cause Death
Lasso di tempo: 7 days
|
7 days
|
|
|
Recurrent PE
Lasso di tempo: 7 days
|
7 days
|
|
|
Persistent Dyspnea
Lasso di tempo: 6 months
|
Persistent Dyspnea Assessed by the Medical Research Council (MRC) Dyspnea Scale |
6 months
|
|
Functional outcome
Lasso di tempo: 6 months
|
Functional status will be assessed using the Post-Venous Thromboembolism Functional Status (PVFS) Scale, which measures limitations in usual activities and daily functioning after venous thromboembolism. The scale ranges from grade 0 (no functional limitations) to grade 4 (severe functional limitations requiring assistance with activities of daily living). Higher grades indicate greater functional impairment. Grade D indicates death before the scheduled assessment. |
6 months
|
|
Persistent Right Ventricular Dysfunction
Lasso di tempo: 6 months
|
Persistent right ventricular dysfunction is defined as an intermediate or high probability of pulmonary hypertension on echocardiography according to the European Society of Cardiology (ESC) criteria. |
6 months
|
|
Chronic thromboembolic pulmonary disease (CTEPD) and/or Chronic thromboembolic pulmonary hypertension (CTEPH)
Lasso di tempo: 12 months
|
12 months
|
|
|
Major bleeding
Lasso di tempo: 30 days
|
Major bleeding will be defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria as fatal bleeding, symptomatic bleeding in a critical area or organ, a decrease in hemoglobin of ≥2 g/dL, or transfusion of ≥2 units of whole blood or red blood cells. The number of participants experiencing major bleeding will be recorded |
30 days
|
|
Clinically relevant non-major bleeding
Lasso di tempo: 30 days
|
Clinically relevant non-major bleeding will be defined according to ISTH criteria as bleeding that does not meet the criteria for major bleeding but requires medical intervention, leads to hospitalization or an increased level of care, or prompts a face-to-face evaluation by a healthcare professional. The number of participants experiencing clinically relevant non-major bleeding will be recorded. |
30 days
|
|
Minor bleeding
Lasso di tempo: 30 days
|
Minor bleeding will be defined as any overt bleeding event that does not meet the criteria for major bleeding or clinically relevant non-major bleeding and does not require medical attention. The number of participants experiencing minor bleeding will be recorded. |
30 days
|
Collaboratori e investigatori
Sponsor
Sponsor
Investigatori
Investigatori
- Investigatore principale: Changming Xiong, Prof., Chinese Academy of Medical Sciences, Fuwai Hospital
- Investigatore principale: Zhenguo Zhai, Prof., China-Japan Friendship Hospital
Pubblicazioni e link utili
Pubblicazioni generali
- Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; "MOPETT" Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027. Epub 2012 Oct 24.
- Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
- Wang C, Zhai Z, Yang Y, Wu Q, Cheng Z, Liang L, Dai H, Huang K, Lu W, Zhang Z, Cheng X, Shen YH; China Venous Thromboembolism (VTE) Study Group. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010 Feb;137(2):254-62. doi: 10.1378/chest.09-0765. Epub 2009 Sep 9.
- Sanchez O, Charles-Nelson A, Ageno W, Barco S, Binder H, Chatellier G, Duerschmied D, Empen K, Ferreira M, Girard P, Huisman MV, Jimenez D, Katsahian S, Kozak M, Lankeit M, Meneveau N, Pruszczyk P, Petris A, Righini M, Rosenkranz S, Schellong S, Stefanovic B, Verhamme P, de Wit K, Vicaut E, Zirlik A, Konstantinides SV, Meyer G; PEITHO-3 Investigators. Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial. Thromb Haemost. 2022 May;122(5):857-866. doi: 10.1055/a-1653-4699. Epub 2021 Oct 31.
- Liu L, Li C, Shi L, Ma D, Zhang Z, Bao H, Li C, Li L, Wang M, Ma Z, Zhang J. Efficacy and safety of low-dose thrombolysis in acute intermediate-high risk pulmonary thromboembolism complicated by PaO2/FiO2 < 300. Front Med (Lausanne). 2026 Jul 9;13:1849541. doi: 10.3389/fmed.2026.1849541. eCollection 2026.
- Yilmaz ES, Uzun O. Low-dose thrombolysis for submassive pulmonary embolism. J Investig Med. 2021 Dec;69(8):1439-1446. doi: 10.1136/jim-2021-001816. Epub 2021 Jun 7.
- Zhang LY, Gao BA, Jin Z, Xiang GM, Gong Z, Zhang TT, Lu HF, Wang YQ, Gong Y, Lu C, Huang WL. Clinical efficacy of low dose recombinant tissue-type plasminogen activator for the treatment of acute intermediate-risk pulmonary embolism. Saudi Med J. 2018 Nov;39(11):1090-1095. doi: 10.15537/smj.2018.11.22717.
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Inizio studio
Completamento primario (Stimato)
Completamento primario
Completamento dello studio (Stimato)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie vascolari
- Malattia cardiovascolare
- Malattie delle vie respiratorie
- Malattie polmonari
- Embolia e Trombosi
- Embolia
- Embolia polmonare
- Aminoacidi, peptidi e proteine
- Proteine
- Fattori biologici
- Idrolasi
- Enzimi
- Enzimi e coenzimi
- Proteine del sangue
- Endopeptidasi
- Idrolasi peptidiche
- Endopeptidasi serina
- Proteasi di serina
- Attivatori del plasminogeno
- Fattori di coagulazione del sangue
- Attivatore tissutale del plasminogeno
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- 2026ZD0556203-02
- 2026ZD0556203 (Altro numero di sovvenzione/finanziamento: Noncommunicable Chronic Diseases-National Science and Technology Major Project)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .