[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100655952":3},{"organization":4,"outcomesModule":7,"designInfo":104,"detailedDescription":115,"studyPopulation":109,"armGroups":116,"interventions":129,"overallOfficials":143,"centralContacts":148,"locations":157,"responsibleParty":408,"collaborators":410,"id":423,"slug":424,"hasResults":425,"nctId":426,"briefTitle":427,"officialTitle":428,"acronym":429,"eligibilityCriteria":430,"healthyVolunteers":425,"sex":431,"minAge":432,"maxAge":109,"enrollmentInfo":433,"targetDuration":109,"studyType":436,"phases":437,"briefSummary":439,"conditions":440,"keywords":442,"overallStatus":448,"whyStopped":109,"lastUpdateSubmitDate":449,"lastUpdatePostDateStruct":450,"startDateStruct":453,"completionDateStruct":455,"leadSponsor":457,"locationsCount":458},{"fullName":5,"class":6},"Sahlgrenska University Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":16,"otherOutcomes":72},[9,13],{"measure":10,"description":11,"timeFrame":12},"Incidence of composite efficacy endpoint","Incidence of a composite endpoint comprising all-cause mortality within 7 days, cardiopulmonary resuscitation and\u002For 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",{"measure":14,"description":15,"timeFrame":12},"Key secondary endpoint - Incidence of severe clinically significant bleeding","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.",[17,21,24,27,31,35,39,42,45,48,51,55,59,62,66,69],{"measure":18,"description":19,"timeFrame":20},"All-cause mortality","Incidence of death from any cause.","At 7 days and 30 days after randomization",{"measure":22,"description":23,"timeFrame":20},"Pulmonary embolism-related mortality","Incidence of pulmonary embolism-related death.",{"measure":25,"description":26,"timeFrame":12},"Cardiopulmonary resuscitation and\u002For VA-ECMO","Incidence of cardiopulmonary resuscitation and\u002For veno-arterial extracorporeal membrane oxygenation.",{"measure":28,"description":29,"timeFrame":30},"Incidence of clinical deterioration","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",{"measure":32,"description":33,"timeFrame":34},"Lack of clinical improvement assessed by SCAI SHOCK stage and oxygen requirement","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",{"measure":36,"description":37,"timeFrame":38},"Time to clinical stabilization based on predefined hemodynamic and respiratory criteria","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",{"measure":40,"description":41,"timeFrame":20},"Incidence of recurrent pulmonary embolism","Incidence of objectively confirmed recurrent pulmonary embolism.",{"measure":43,"description":44,"timeFrame":12},"Initiation of invasive or non-invasive mechanical ventilation","Incidence of initiation of invasive or non-invasive mechanical ventilation.",{"measure":46,"description":47,"timeFrame":12},"Win ratio for efficacy","Win ratio based on all-cause mortality, cardiopulmonary resuscitation and\u002For VA-ECMO, clinical deterioration, lack of clinical improvement, recurrent pulmonary embolism, and time to clinical stabilization.",{"measure":49,"description":50,"timeFrame":12},"Net clinical benefit","Composite net clinical benefit including severe clinically significant bleeding, all-cause mortality, cardiopulmonary resuscitation and\u002For VA-ECMO, recurrent pulmonary embolism, clinical deterioration, and lack of clinical improvement.",{"measure":52,"description":53,"timeFrame":54},"Rescue treatment","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",{"measure":56,"description":57,"timeFrame":58},"ICU or high-dependency unit length of stay in days","Length of stay in intensive care unit and\u002For high-dependency unit.","Within 30 days after randomization",{"measure":60,"description":61,"timeFrame":58},"Hospital length of stay","Length of hospital stay.",{"measure":63,"description":64,"timeFrame":65},"Major bleeding","Incidence of major bleeding according to International Society on Thrombosis and Haemostasis criteria.","At 48 hours, 7 days, and 30 days after randomization",{"measure":67,"description":68,"timeFrame":65},"Bleeding requiring urgent medical intervention","Incidence of severe bleeding requiring urgent medical intervention.",{"measure":70,"description":71,"timeFrame":12},"Intracerebral bleeding","Incidence of intracerebral bleeding.",[73,76,77,81,84,87,91,94,97,100],{"measure":74,"description":19,"timeFrame":75},"All-cause mortality at 12 months","At 12 months after randomization",{"measure":75,"description":41,"timeFrame":75},{"measure":78,"description":79,"timeFrame":80},"Persistent dyspnea assessed using the modified Medical Research Council scale","Persistent dyspnea assessed using the modified Medical Research Council scale.","At 3 months and 12 months after randomization",{"measure":82,"description":83,"timeFrame":80},"Functional status assessed using the Post-VTE Functional Status Scale","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.",{"measure":85,"description":86,"timeFrame":80},"Exercise tolerance assessed using the 6-minute walk test","Exercise tolerance assessed using the 6-minute walk test, reported as distance walked in meters. A greater distance indicates better exercise tolerance.",{"measure":88,"description":89,"timeFrame":90},"Persistent right ventricular dysfunction assessed by echocardiography","Persistent right ventricular dysfunction according to echocardiography report, when performed as clinically indicated.","At 3 months and\u002For 12 months after randomization",{"measure":92,"description":93,"timeFrame":80},"Pulmonary embolism-specific quality of life assessed using the PEmb-QoL questionnaire","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.",{"measure":95,"description":96,"timeFrame":80},"Health-related quality of life assessed using EQ-5D-5L","Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument.",{"measure":98,"description":99,"timeFrame":75},"Chronic thromboembolic pulmonary hypertension","Incidence of chronic thromboembolic pulmonary hypertension.",{"measure":101,"description":102,"timeFrame":103},"Health care resource utilization","Cost of health care resource utilization during the 12-month follow-up period.","During 12 months after randomization",{"allocation":105,"interventionModel":106,"interventionModelDescription":107,"primaryPurpose":108,"observationalModel":109,"timePerspective":109,"maskingInfo":110},"RANDOMIZED","PARALLEL","Participants will be randomized in a 1:1 ratio to reduced-dose alteplase or standard full-dose alteplase.","TREATMENT",null,{"masking":111,"maskingDescription":112,"whoMasked":113},"SINGLE","The trial is open-label because alteplase dose and administration regimen differ between treatment groups and immediate clinical management requires knowledge of treatment allocation. The primary endpoint and key secondary endpoint will be adjudicated by an independent central Critical Events Committee blinded to treatment allocation. The trial statistician responsible for the final analyses will remain blinded until database lock and completion of all prespecified analyses",[114],"OUTCOMES_ASSESSOR","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.\n\nREDSTEM 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.\n\nThe 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.",[117,123],{"label":118,"type":119,"description":120,"interventionNames":121},"Reduced-Dose Alteplase","EXPERIMENTAL","Participants randomized to reduced-dose systemic thrombolysis will receive alteplase 0.6 mg\u002Fkg body weight, up to a maximum dose of 50 mg, administered intravenously over 15 minutes.",[122],"Drug: Reduced-dose alteplase",{"label":124,"type":125,"description":126,"interventionNames":127},"Full-Dose Alteplase","ACTIVE_COMPARATOR","Participants randomized to standard full-dose systemic thrombolysis will receive alteplase 1.5 mg\u002Fkg 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.",[128],"Drug: Full-dose alteplase",[130,137],{"type":131,"name":132,"description":133,"armGroupLabels":134,"otherNames":135},"DRUG","Reduced-dose alteplase","Alteplase 0.6 mg\u002Fkg body weight, maximum 50 mg, administered as an intravenous infusion over 15 minutes",[118],[136],"Reduced-dose systemic thrombolysis, Low-dose alteplase, tPA",{"type":131,"name":138,"description":139,"armGroupLabels":140,"otherNames":141},"Full-dose alteplase","Alteplase 1.5 mg\u002Fkg 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.",[124],[142],"Full-dose systemic thrombolysis, Standard-dose alteplase, tPA",[144],{"name":145,"affiliation":146,"role":147},"Kristina Svennerholm","Sahlgrenska University Hospital \u002F University of Gothenburg","PRINCIPAL_INVESTIGATOR",[149,154],{"name":150,"role":151,"phone":152,"phoneExt":109,"email":153},"Kristina Svennerholm, MD PhD","CONTACT","+46313421000","kristina.svennerholm@vgregion.se",{"name":155,"role":151,"phone":152,"phoneExt":109,"email":156},"Annika Odenstedt, Coordinator","annika.odenstedt@vgregion.se",[158,172,186,198,210,217,229,241,257,268,276,287,298,309,320,331,344,355,363,371,378,386,397],{"facility":159,"status":109,"city":160,"state":109,"zip":109,"country":161,"countryCode":162,"cosmosGeoPoint":163,"geoPoint":168,"contacts":169},"Rigshospitalet","Copenhagen","Denmark","DK",{"type":164,"coordinates":165},"Point",[166,167],12.56553,55.67594,{"lat":167,"lon":166},[170],{"name":171,"role":151,"phone":109,"phoneExt":109,"email":109},"Jesper Kjaergaard, MD, PhD",{"facility":173,"status":109,"city":174,"state":109,"zip":175,"country":176,"countryCode":177,"cosmosGeoPoint":178,"geoPoint":182,"contacts":183},"Haukeland University Hospital","Bergen","5021","Norway","NO",{"type":164,"coordinates":179},[180,181],5.32415,60.39299,{"lat":181,"lon":180},[184],{"name":185,"role":151,"phone":109,"phoneExt":109,"email":109},"Lasse Melvear Gii, MD, PhD",{"facility":187,"status":109,"city":188,"state":109,"zip":189,"country":176,"countryCode":177,"cosmosGeoPoint":190,"geoPoint":194,"contacts":195},"Drammen Hospital","Drammen","3004",{"type":164,"coordinates":191},[192,193],10.20449,59.74389,{"lat":193,"lon":192},[196],{"name":197,"role":151,"phone":109,"phoneExt":109,"email":109},"Jonas Pivoriunas, MD, PhD",{"facility":199,"status":109,"city":200,"state":109,"zip":201,"country":176,"countryCode":177,"cosmosGeoPoint":202,"geoPoint":206,"contacts":207},"Ostfold Hisptal","Grålum","1714",{"type":164,"coordinates":203},[204,205],11.06668,59.29048,{"lat":205,"lon":204},[208],{"name":209,"role":151,"phone":109,"phoneExt":109,"email":109},"Hans Joakim Myklebust-Hansen, MD",{"facility":211,"status":109,"city":212,"state":109,"zip":213,"country":176,"countryCode":177,"cosmosGeoPoint":109,"geoPoint":109,"contacts":214},"Akershus University Hospital","Lörenskog","1478",[215],{"name":216,"role":151,"phone":109,"phoneExt":109,"email":109},"Hamza Nahoui, MD",{"facility":218,"status":109,"city":219,"state":109,"zip":220,"country":176,"countryCode":177,"cosmosGeoPoint":221,"geoPoint":225,"contacts":226},"Oslo University Hospital, Ullevål","Oslo","0450",{"type":164,"coordinates":222},[223,224],10.74609,59.91273,{"lat":224,"lon":223},[227],{"name":228,"role":151,"phone":109,"phoneExt":109,"email":109},"Mari Asphjell Björnaas, MD, PhD",{"facility":230,"status":109,"city":231,"state":109,"zip":232,"country":176,"countryCode":177,"cosmosGeoPoint":233,"geoPoint":237,"contacts":238},"Stavanger University Hospital","Stavanger","4021",{"type":164,"coordinates":234},[235,236],5.73332,58.97005,{"lat":236,"lon":235},[239],{"name":240,"role":151,"phone":109,"phoneExt":109,"email":109},"Trond Johan Cooper, MD",{"facility":5,"status":109,"city":242,"state":243,"zip":244,"country":245,"countryCode":246,"cosmosGeoPoint":247,"geoPoint":251,"contacts":252},"Gothenburg","Västra Götaland County","413 45","Sweden","SE",{"type":164,"coordinates":248},[249,250],11.96679,57.70716,{"lat":250,"lon":249},[253,255],{"name":254,"role":151,"phone":109,"phoneExt":109,"email":153},"Kristina Svennerholm, MD, PhD",{"name":256,"role":151,"phone":109,"phoneExt":109,"email":156},"Annika Odenstedt",{"facility":258,"status":109,"city":259,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":260,"geoPoint":264,"contacts":265},"Falun Hospital","Falun",{"type":164,"coordinates":261},[262,263],15.62597,60.60357,{"lat":263,"lon":262},[266],{"name":267,"role":151,"phone":109,"phoneExt":109,"email":109},"Jessica Silfverberg, MD",{"facility":269,"status":109,"city":242,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":270,"geoPoint":272,"contacts":273},"Sahlgrenska University Hospital\u002FÖstra",{"type":164,"coordinates":271},[249,250],{"lat":250,"lon":249},[274],{"name":275,"role":151,"phone":109,"phoneExt":109,"email":109},"Katarina Glise Sandblad, MD, PhD",{"facility":277,"status":109,"city":278,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":279,"geoPoint":283,"contacts":284},"Ryhov County Hospital","Jönköping",{"type":164,"coordinates":280},[281,282],14.15618,57.78145,{"lat":282,"lon":281},[285],{"name":286,"role":151,"phone":109,"phoneExt":109,"email":109},"Antheia Kissopoulou, MD, PhD",{"facility":288,"status":109,"city":289,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":290,"geoPoint":294,"contacts":295},"Skåne University Hospital, Lund","Lund",{"type":164,"coordinates":291},[292,293],13.19321,55.70584,{"lat":293,"lon":292},[296],{"name":297,"role":151,"phone":109,"phoneExt":109,"email":109},"Marcus Ohlsson, MD",{"facility":299,"status":109,"city":300,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":301,"geoPoint":305,"contacts":306},"Skåne University Hospital, Malmö","Malmö",{"type":164,"coordinates":302},[303,304],13.00073,55.60587,{"lat":304,"lon":303},[307],{"name":308,"role":151,"phone":109,"phoneExt":109,"email":109},"Marcus Ohlsson, MD, PhD",{"facility":310,"status":109,"city":311,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":312,"geoPoint":316,"contacts":317},"Sahlgrenska University Hospital\u002FMölndal","Mölndal",{"type":164,"coordinates":313},[314,315],12.01378,57.6554,{"lat":315,"lon":314},[318],{"name":319,"role":151,"phone":109,"phoneExt":109,"email":109},"Louise Martinell, MD, PhD",{"facility":321,"status":109,"city":322,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":323,"geoPoint":327,"contacts":328},"Norrtälje Hospital","Norrtälje",{"type":164,"coordinates":324},[325,326],18.70496,59.75799,{"lat":326,"lon":325},[329],{"name":330,"role":151,"phone":109,"phoneExt":109,"email":109},"Sune Forsberg, MD, PhD",{"facility":332,"status":109,"city":333,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":334,"geoPoint":338,"contacts":339},"Skaraborgs Hospital Skövde","Skövde",{"type":164,"coordinates":335},[336,337],13.84506,58.39118,{"lat":337,"lon":336},[340,342],{"name":341,"role":151,"phone":109,"phoneExt":109,"email":109},"Freyr Einarsson, MD",{"name":343,"role":151,"phone":109,"phoneExt":109,"email":109},"Erik Ullemark, MD",{"facility":345,"status":109,"city":346,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":347,"geoPoint":351,"contacts":352},"Capio S:t Göran's Hospital","Stockholm",{"type":164,"coordinates":348},[349,350],18.06871,59.32938,{"lat":350,"lon":349},[353],{"name":354,"role":151,"phone":109,"phoneExt":109,"email":109},"Rickard Markgren, MD, PhD",{"facility":356,"status":109,"city":346,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":357,"geoPoint":359,"contacts":360},"Danderyd Hospital",{"type":164,"coordinates":358},[349,350],{"lat":350,"lon":349},[361],{"name":362,"role":151,"phone":109,"phoneExt":109,"email":109},"Nina Olausson, MD, PhD",{"facility":364,"status":109,"city":346,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":365,"geoPoint":367,"contacts":368},"Karolinska University Hospital, Huddinge",{"type":164,"coordinates":366},[349,350],{"lat":350,"lon":349},[369],{"name":370,"role":151,"phone":109,"phoneExt":109,"email":109},"Therese Djärv, MD, PhD",{"facility":372,"status":109,"city":346,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":373,"geoPoint":375,"contacts":376},"Karolinska University Hospital, Solna",{"type":164,"coordinates":374},[349,350],{"lat":350,"lon":349},[377],{"name":370,"role":151,"phone":109,"phoneExt":109,"email":109},{"facility":379,"status":109,"city":346,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":380,"geoPoint":382,"contacts":383},"Södersjukhuset, Stockholm South General Hospital",{"type":164,"coordinates":381},[349,350],{"lat":350,"lon":349},[384],{"name":385,"role":151,"phone":109,"phoneExt":109,"email":109},"Jacob Hollenberg, MD, PhD",{"facility":387,"status":109,"city":388,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":389,"geoPoint":393,"contacts":394},"University Hospital of Umeå","Umeå",{"type":164,"coordinates":390},[391,392],20.25972,63.82842,{"lat":392,"lon":391},[395],{"name":396,"role":151,"phone":109,"phoneExt":109,"email":109},"Johanna Pennlert, MD, PhD",{"facility":398,"status":109,"city":399,"state":109,"zip":109,"country":245,"countryCode":246,"cosmosGeoPoint":400,"geoPoint":404,"contacts":405},"Uppsala University Hospital","Uppsala",{"type":164,"coordinates":401},[402,403],17.63889,59.85882,{"lat":403,"lon":402},[406],{"name":407,"role":151,"phone":109,"phoneExt":109,"email":109},"Sofia Vikman, MD, PhD",{"type":147,"investigatorFullName":145,"investigatorTitle":409,"investigatorAffiliation":5,"oldNameTitle":109,"oldOrganization":109},"Principal investigator",[411,413,415,417,419,421],{"name":412,"class":6},"Göteborg University",{"name":414,"class":6},"Leiden University Medical Center",{"name":416,"class":6},"Assistance Publique - Hôpitaux de Paris",{"name":418,"class":6},"Rigshospitalet, Denmark",{"name":420,"class":6},"University Hospital, Akershus",{"name":422,"class":6},"University of Zurich","100655952","phase-4-reduced-dose-versus-full-dose-alteplase-for-high-risk-pulmonary-embolism-100655952",false,"NCT07816978","Reduced-Dose Versus Full-Dose Alteplase for High-Risk Pulmonary Embolism","Reduced-Dose Versus Full-Dose Systemic Thrombolysis for High-Risk Pulmonary Embolism: A Multicentre, Randomised, Open-Label, Blinded-Endpoint Trial","REDSTEM","Inclusion Criteria:\n\n1. Participant aged 18 years or older.\n2. 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.\n3. High risk for early death, defined by at least one of the following:\n\n   1. High-risk pulmonary embolism according to European Society of Cardiology criteria:\n\n      * Cardiac arrest with return of spontaneous circulation;\n      * Obstructive shock, defined as systolic blood pressure \\\u003C90 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\u002FL, altered mental status, or cold clammy skin;\n      * Persistent hypotension, defined as systolic blood pressure \\\u003C90 mmHg or a drop in systolic blood pressure ≥40 mmHg for longer than 15 minutes, not caused by new-onset arrhythmia, hypovolemia, or sepsis.\n   2. Abnormal right ventricular function on echocardiography or computed tomography pulmonary angiography, defined as right ventricular\u002Fleft 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\u002Fmin, high-flow nasal oxygen, or non-invasive ventilation with FiO2 ≥60% to reach oxygen saturation ≥94%.\n4. Female participants of childbearing potential must have a negative urine or serum pregnancy test.\n\nExclusion Criteria:\n\n1. Catastrophic pulmonary embolism, defined as ongoing cardiac arrest and\u002For need for extracorporeal cardiopulmonary resuscitation and\u002For immediate VA-ECMO as judged by the treating physicians.\n2. Known hypersensitivity to alteplase or any of its excipients.\n3. Contraindication to systemic thrombolysis with one or more of the following:\n\n   * History of hemorrhagic stroke;\n   * Ischemic stroke within the previous 6 months;\n   * Central nervous system neoplasm;\n   * Major trauma, major surgery, or major head injury within the previous 3 weeks;\n   * Active life-threatening bleeding, bleeding into a critical organ or area, or known severe bleeding diathesis;\n   * Chronic use of full-dose oral or parenteral anticoagulation before presentation.\n4. The participant has already received reperfusion treatment for the index pulmonary embolism before randomization, including systemic thrombolysis, surgical embolectomy, or catheter-directed intervention.\n5. Pregnancy.\n6. Current participation in another study that would interfere with participation in this trial.\n7. Any other condition that would put the participant at unacceptable risk from the trial interventions as judged by the treating clinician.\n8. In countries where required by national regulations: lack of affiliation to a social security system or equivalent health insurance coverage.","ALL","18 Years",{"count":434,"type":435},400,"ESTIMATED","INTERVENTIONAL",[438],"PHASE4","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.\n\nREDSTEM 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.",[441],"Pulmonary Embolism Acute",[443,444,445,446,447],"Systemic thrombolysis","Efficacy","Safety","Reduced-dose","Alteplase","NOT_YET_RECRUITING","2026-09-14",{"date":451,"type":452},"2026-09-17","ACTUAL",{"date":454,"type":435},"2026-12-01",{"date":456,"type":435},"2031-01-31",{"name":5,"class":6},23]