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

Olivier Sanchez, Anaïs Charles-Nelson, Walter Ageno, Stefano Barco, Harald Binder, Gilles Chatellier, Daniel Duerschmied, Klaus Empen, Melanie Ferreira, Philippe Girard, Menno V. Huisman, David Jiménez, Sandrine Katsahian, Matija Kozak, Mareike Lankeit, Nicolas Meneveau, Piotr Pruszczyk, Antoniu Petris, Marc Righini, Stephan RosenkranzSebastian Schellong, Branislav Stefanovic, Peter Verhamme, Kerstin De Wit, Eric Vicaut, Andreas Zirlik, Stavros V. Konstantinides, Guy Meyer

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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.

Original languageEnglish
Pages (from-to)857-866
Number of pages10
JournalThrombosis and Haemostasis
Volume122
Issue number5
DOIs
Publication statusPublished - May 2022
Externally publishedYes

Keywords

  • intermediate-high-risk
  • prognosis
  • pulmonary embolism
  • randomized trial
  • reduced-dose thrombolysis

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