Reduced-dose intravenous thrombolysis for acute intermediate-high-risk pulmonary embolism: rationale and design of the pulmonary embolism international THrOmbolysis (PEITHO)-3 trial

Sanchez, O.; Charles-Nelson, A.; Ageno, W.; Barco, S.; Binder, H.; Chatellier, G.; Duerschmied, D.; Empen, K.; Ferreira, M.; Girard, P.; Huisman, M.V.; Jimenez, D.; Katsahian, S.; Kozak, M.; Lankeit, M.; Meneveau, N.; Pruszczyk, P.; Petris, A.; Righini, M.; Rosenkranz, S.; Schellong, S.; Stefanovic, B.; Verhamme, P.; Wit, K. de; Vicaut, E.; Zirlik, A.; Konstantinides, S.V.; Meyer, G.; PEITHO-3 Investigators

doi:doi:10.1055/a-1653-4699

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...Show moreIntermediate-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.Show less

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Reduced-dose intravenous thrombolysis for acute intermediate-high-risk pulmonary embolism: rationale and design of the pulmonary embolism international THrOmbolysis (PEITHO)-3 trial