The PEITHO-3 trial is a planned randomized controlled trial designed to evaluate whether reduced-dose alteplase improves clinical outcomes compared to standard heparin in patients with acute intermediate-high-risk pulmonary embolism.
RCT (n=650)
Double-blind
Randomized
Yes
Does a reduced-dose alteplase regimen reduce the composite of all-cause death, hemodynamic decompensation, or PE recurrence compared to standard heparin anticoagulation in patients with intermediate-high-risk pulmonary embolism?
The PEITHO-3 trial is designed to evaluate whether reduced-dose alteplase provides a better balance of efficacy and safety compared to standard heparin in intermediate-high-risk pulmonary embolism.
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.
Sanchez et al. (2021) conducted an RCT in Acute intermediate-high-risk pulmonary embolism (n=650). Alteplase vs. Placebo (both arms receive standard heparin anticoagulation) was evaluated on Composite of all-cause death, hemodynamic decompensation, or objectively confirmed recurrent PE within 30 days of randomization. The PEITHO-3 trial is a planned randomized controlled trial designed to evaluate whether reduced-dose alteplase improves clinical outcomes compared to standard heparin in patients with acute intermediate-high-risk pulmonary embolism.