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DOI: 10.1055/a-1653-4699
Reduced-Dose Intravenous Thrombolysis for Acute Intermediate–High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial
Funding The work of Stavros Konstantinides was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003 and 01EO1503). The authors are responsible for the contents of this publication.PEITHO-3 is an independent, investigator-initiated trial. The study is being supported by public funding, specifically by grants from the French Ministry of Health (PHRCN-16–0580), the German Research Foundation (Deutsche Forschungsgemeinschaft; KO 1939/3–1), the Canadian Institutes of Health Research and the Spanish Ministry of Science and Innovation. In addition, the sponsor, Assistance Publique – Hôpitaux de Paris, has obtained the study drug and a grant from the market authorization holder of alteplase, Boehringer Ingelheim. The authors are solely responsible for the design and conduct of the trial, for all study analyses, and for the drafting and editing of reports and publications and their final contents.
Abstract
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 ≤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.
Keywords
pulmonary embolism - intermediate–high-risk - reduced-dose thrombolysis - prognosis - randomized trial† Deceased.
Publikationsverlauf
Eingereicht: 22. Juni 2021
Angenommen: 28. Juli 2021
Accepted Manuscript online:
24. September 2021
Artikel online veröffentlicht:
31. Oktober 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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