Catheter-directed Thrombolysis in Intermediate-high Risk Acute Pulmonary Embolism

The registry criteria, word for word

What the trial wants to find out

Background: Intermediate-high risk acute pulmonary embolism (PE) remains associated with substantial mortality despite standard anticoagulation therapy. Previous efforts to decrease mortality in these patients via administration of systemic thrombolysis have failed due to an increased rate of major bleeding complications. Catheter-directed thrombolysis (CDT) has already shown some promising results in terms of efficacy and safety, including the results of our randomized pilot study. However, large randomized trials with clinical endpoints comparing catheter-directed local thrombolysis versus standard anticoagulation therapy are still lacking, thus the treatment of intermediate-high risk acute PE patients has not changed for decades. Hypothesis: Catheter-directed local thrombolysis is superior to standard anticoagulation therapy in the treatment of intermediate-high risk acute pulmonary embolism, with no additional safety concerns. Statistical considerations: Estimated incidence of the primary endpoint of 1.5% in the CDT group and 6.0% in the standard anticoagulation group, 80% power for each arm with a 2-sided alpha of 0.05. Five hundred fifty-eight should provide the requisite number of events. Statistical Analysis - Intention to Treat. Methods and Results: A Multicentre, Randomized Trial of Catheter-directed thrombolysis in intermediate-high risk acute pulmonary embolism (PRAGUE-26) is a noncommercial, multicentre, randomized, controlled parallel-group comparison trial. The trial plans to include 558 patients with intermediate-high risk acute PE. Patients will be randomized in a 1:1 ratio to CDT or to standard anticoagulation therapy. The primary outcome of the study is a clinical composite of all-cause mortality, PE recurrence or cardiorespiratory decompensation, within 7 days of randomization. Secondary objectives cover all bleeding complications, functional and patient-reported outcomes over a follow-up period of 24 months and cost-effectiveness analysis.

The 2 groups in the trial

• Catheter-Directed ThrombolysisTreatment being tested

  Venous access should be obtained under ultrasound guidance (via the common femoral vein). The use of a double-lumen 8-Fr introducer (single access site) or two 4-Fr introducers (two ipsilateral access sites) is at the discretion of the operator. After each thrombolytic catheter placement into left and/or right pulmonary artery, a subsequent bolus of 1mg of Alteplase (Actilyse, Boehringer Ingelheim)/catheter is administered, followed by continuous infusion at 1 mg/h/catheter for 9 h (total dose 10mg for unilateral and 20mg for bilateral PE). Intravenous unfractionated heparin is continued to a target activated partial thromboplastin time (aPTT) of 50-60 s. After the end of local thrombolysis, the catheters are removed and anticoagulation with unfractionated heparin continues.

  Treatment: Thrombolytic

• Standard AnticoagulationExisting treatment, for comparison

  Before randomization, all patients are treated with intravenous unfractionated heparin (to a target aPTT of 70-90 s) or subcutaneous LMWH (the full therapeutic dose). For patients in the CDT group, the anticoagulation treatment was is described above; among CDT patients who received LMWH, the procedure should be postponed for 8 h after the last dose of LMWH. Patients in the standard care group continue therapeutic anticoagulation with either unfractionated heparin or LMWH. Subsequent change for oral anticoagulation is at the discretion of the treating physician (not earlier than 24 hours post-randomization).