Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial

被引：77

作者：

Sanchez, Olivier ^{[1
,2
,3
,4
]}

Charles-Nelson, Anais ^{[5
,6
]}

Ageno, Walter ^{[7
]}

Barco, Stefano ^{[8
,9
]}

Binder, Harald ^{[10
,11
]}

Chatellier, Gilles ^{[3
,5
,6
]}

Duerschmied, Daniel ^{[12
]}

Empen, Klaus ^{[13
]}

Ferreira, Melanie ^{[14
]}

Girard, Philippe ^{[4
,15
]}

Huisman, Menno, V ^{[16
]}

Jimenez, David ^{[17
]}

Katsahian, Sandrine ^{[3
,5
,6
,18
]}

Kozak, Matija ^{[19
]}

Lankeit, Mareike ^{[8
,20
,21
]}

Meneveau, Nicolas ^{[4
,22
,23
]}

Pruszczyk, Piotr ^{[24
]}

Petris, Antoniu ^{[25
]}

Righini, Marc ^{[26
]}

Rosenkranz, Stephan ^{[27
,28
]}

Schellong, Sebastian ^{[29
]}

Stefanovic, Branislav ^{[30
]}

Verhamme, Peter ^{[31
]}

de Wit, Kerstin ^{[32
]}

Vicaut, Eric ^{[33
]}

Zirlik, Andreas ^{[34
]}

Konstantinides, Stavros, V ^{[8
,35
]}

Meyer, Guy ^{[1
,3
,4
]}

机构：

[1] Univ Paris, Hop Europeen Georges Pompidou, AP HP, AP HP Ctr,Serv Pneumol & Soins Intensifs, Paris, France

[2] INSERM UMR S 1140 Innovative Therapies Hemostasis, Paris, France

[3] Univ Paris, Paris, France

[4] FCRIN INNOVTE, St Etienne, France

[5] Hop Europeen Georges Pompidou, AP HP, AP HP Ctr, Unite Rech Clin, Paris, France

[6] Ctr Invest Clin 1418 CIC1418 Epidemiol Clin, INSERM, Paris, France

[7] Univ Insubria, Dept Med & Surg, Varese, Italy

[8] Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis CTH, Mainz, Germany

[9] Univ Hosp Zurich, Clin Angiol, Zurich, Switzerland

[10] Univ Freiburg, Fac Med, Inst Med Biometry & Stat, Freiburg, Germany

[11] Univ Freiburg, Med Ctr, Freiburg, Germany

[12] Univ Freiburg, Univ Heart Ctr Freiburg Bad Krozingen, Fac Med, Dept Cardiol & Angiol 1, Freiburg, Germany

[13] Stadt Klinikum Dessau, Dept Internal Med, Dessau, Germany

[14] Hosp Garcia Orta, Internal Med Dept, Almada, Portugal

[15] Inst Mutualiste Montsouris, Dept Thorac, Paris, France

[16] Leiden Univ Med Ctr, Dept Thrombosis & Hemostasis, Dutch Thrombosis Network, Leiden, Netherlands

[17] Univ Alcala IRYCIS, Ramon y Cajal Hosp, Dept Resp Dis, CIBER Enfermedades Resp CIBERES, Madrid, Spain

[18] Ctr Rech Cordeliers, INSERM UMR S 1138 Equipe 22, Paris, France

[19] Univ Med Ctr, Dept Vasc Dis, Ljubljana, Slovenia

[20] Vivantes Klinikum Friedrichshain, Dept Internal Med Vasc Med & Haemostaseol, Berlin, Germany

[21] Univ Med Ctr Goettingen, Clin Cardiol & Pneumol, Gottingen, Germany

[22] Univ Hosp Jean Minjoz, Dept Cardiol, Besancon, France

[23] Univ Burgundy Franche Comte, EA3920, Besancon, France

[24] Med Univ Warsaw, Dept Internal Med & Cardiol, Warsaw, Poland

[25] Grigore T Popa Univ Med & Pharm Iasi, Cardiol Clin, St Spiridon Cty Clin Emergency Hosp, Iasi, Romania

[26] Univ Geneva, Geneva Univ Hosp, Div Angiol & Haemostasis, Geneva, Switzerland

[27] Cologne Univ, Dept Internal Med 3, Heart Ctr, Cologne, Germany

[28] Cologne Univ, Cologne Cardiovasc Res Ctr CCRC, Heart Ctr, Cologne, Germany

[29] Municipal Hosp Dresden, Dept Internal Med 2, Dresden, Germany

[30] Univ Belgrade, Univ Clin Ctr Serbia, Emergency Ctr, Cardiol Clin,Sch Med, Belgrade, Serbia

[31] Univ Hosp Leuven, Dept Cardiovasc Med, Vasc Med & Haemostasis, Leuven, Belgium

[32] McMaster Univ, Dept Med, Hamilton, ON, Canada

[33] Univ Paris 07, AP HP, Unite Rech Clin St Louis Lariboisiere, Paris, France

[34] Med Univ Graz, Dept Internal Med, Div Cardiol, Graz, Austria

[35] Democritus Univ Thrace, Dept Cardiol, Alexandroupolis, Greece

来源：

THROMBOSIS AND HAEMOSTASIS | 2022年 / 122卷 / 05期

基金：

加拿大健康研究院;

关键词：

pulmonary embolism; intermediate-high-risk; reduced-dose thrombolysis; prognosis; randomized trial; PLASMINOGEN-ACTIVATOR; RANDOMIZED-TRIAL; MULTICENTER TRIAL; EUROPEAN-SOCIETY; SINGLE-ARM; VALIDATION; ALTEPLASE; BOLUS; PROGNOSTICATION; STRATIFICATION;

D O I：

10.1055/a-1653-4699

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure <= 110mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations.

引用

页码：857 / 866

页数：10

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[11] EkoSonic® endovascular system and other catheter-directed treatment reperfusion strategies for acute pulmonary embolism: overview of efficacy and safety outcomes [J].