Reduced-Dose Intravenous Thrombolysis for Acute Intermediate–High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial-Reference-Cited by-同舟云学术

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

Published:2021-09-24 Issue: Volume: Page:
ISSN:0340-6245
Container-title:Thrombosis and Haemostasis
language:en
Short-container-title:Thromb Haemost

Author:

Sanchez Olivier¹²³⁴,Charles-Nelson Anaïs⁵⁶,Ageno Walter⁷,Barco Stefano⁸⁹^ORCID,Binder Harald¹⁰,Chatellier Gilles³⁵⁶,Duerschmied Daniel¹¹,Empen Klaus¹²,Ferreira Melanie¹³,Girard Philippe⁴¹⁴,Huisman Menno V.¹⁵,Jiménez David¹⁶,Katsahian Sandrine³⁵⁶¹⁷,Kozak Matija¹⁸,Lankeit Mareike⁸¹⁹²⁰,Meneveau Nicolas⁴²¹²²,Pruszczyk Piotr²³,Petris Antoniu²⁴,Righini Marc²⁵,Rosenkranz Stephan²⁶,Schellong Sebastian²⁷,Stefanovic Branislav²⁸,Verhamme Peter²⁹^ORCID,de Wit Kerstin³⁰,Vicaut Eric³¹,Zirlik Andreas³²,Konstantinides Stavros V.⁸³³^ORCID,Meyer Guy¹³⁴,

Affiliation:

1. AP-HP, hôpital européen Georges-Pompidou, Service de Pneumologie et de Soins Intensifs, APHP.Centre - Université de Paris, Paris, France

2. INSERM UMR S 1140 Innovative Therapies in Hemostasis, Paris, France

3. Université de Paris, Paris, France

4. FCRIN INNOVTE, St-Etienne, France

5. AP-HP, hôpital européen Georges-Pompidou, Unité de Recherche Clinique, APHP.Centre, Paris, France

6. INSERM, Centre d'Investigation Clinique 1418 (CIC1418) Épidémiologie Clinique, Paris, France

7. Department of Medicine and Surgery, University of Insubria, Varese, Italy

8. Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Mainz, Germany

9. Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland

10. Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany

11. Department of Cardiology and Angiology I, University Heart Center Freiburg - Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany

12. Department of Internal Medicine, Städtisches Klinikum Dessau, Germany

13. Internal Medicine Department, Hospital Garcia de Orta, Almada, Portugal

14. Département Thoracique, Institut Mutualiste Montsouris, Paris, France

15. Department of Thrombosis and Hemostasis, Leiden University Medical Center, Dutch Thrombosis Network, Leiden, The Netherlands

16. Department of Respiratory Diseases, Ramon y Cajal Hospital, Universidad de Alcalá (IRYCIS), CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain

17. INSERM UMR_S 1138 équipe 22, Centre de Recherche des Cordeliers, Paris, France

18. Department of Vascular Diseases, University Medical Center, Ljubljana, Slovenia

19. Department of Internal Medicine, Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichshain, Berlin, Germany

20. Clinic of Cardiology and Pneumology, University Medical Center Goettingen, Goettingen, Germany

21. Department of Cardiology, University Hospital Jean Minjoz, Besançon, France

22. EA3920, University of Burgundy Franche-Comté, Besançon, France

23. Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland

24. Grigore T. Popa University of Medicine and Pharmacy Iasi, Cardiology Clinic, “St. Spiridon” County Clinical Emergency Hospital, Iasi, Romania

25. Division of Angiology and Haemostasis, Geneva University Hospital, University of Geneva, Geneva, Switzerland

26. Department III of Internal Medicine and Cologne Cardiovascular Research Center (CCRC), Cologne University Heart Center, Cologne, Germany

27. Department of Internal Medicine 2, Municipal Hospital Dresden, Dresden, Germany

28. Cardiology Clinic, Emergency Center, University Clinical Center of Serbia, School of Medicine University Belgrade, Belgrade, Serbia

29. Vascular Medicine and Haemostasis, Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium

30. Department of Medicine, McMaster University, Hamilton, Ontario, Canada

31. AP-HP, Unité de Recherche Clinique St-Louis-Lariboisière, Université Denis Diderot, Paris, France

32. Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

33. Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece

Abstract

AbstractIntermediate–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 ≤110 mm 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.

Funder

German Federal Ministry of Education and Research

French Ministry of Health

German Research Foundation

Canadian Institutes of Health Research

Spanish Ministry of Science and Innovation

Life Sciences Research Partners (D. Collen Research Foundation), Belgium

Assistance Publique – Hôpitaux de Paris

Publisher

Georg Thieme Verlag KG

Subject

Hematology