Design and rationale of PRAGUE-26: a multicentre, randomised trial of catheter-directed thrombolysis for intermediate-high risk acute pulmonary embolism

he PRAGUE-26 trial (ClinicalTrials.gov: NCT05493163) is a non-industry-sponsored, prospective, multicentre, randomised, active-controlled, unblinded, parallel-group study evaluating clinical outcomes in patients with intermediate-high risk acute pulmonary embolism (PE), comparing catheter-directed thrombolysis (CDT) to standard anticoagulation therapy. Patients with intermediate-high risk acute PE meeting inclusion criteria and not having any exclusion criteria are randomised at a 1:1 ratio to receive either CDT or standard anticoagulation therapy alone. The primary outcome is a clinical composite endpoint of all-cause mortality, PE recurrence, or cardiorespiratory decompensation or collapse, assessed within 7 days of randomisation. The secondary outcomes include bleeding complications, first-line therapy failure, cost-effectiveness analysis, and a broad spectrum of functional and patient-reported outcomes over a 2-year follow-up period. The trial aims to enrol 558 patients. As of 24 November 2024, 258 patients have been randomised. PRAGUE-26 seeks to assess the clinical benefits of simple CDT compared to anticoagulation alone in intermediate-high risk acute PE and aims to contribute to the understanding of this interventional approach. Over the past decade, percutaneous treatment options for intermediate-high and high-risk acute pulmonary embolism (PE) have rapidly evolved. Since 2014, there has been growing evidence for the efficacy and safety of catheter-based treatments for acute PE, supported by data coming from registries, prospective cohorts, and small randomised controlled trials (RCTs)1. However, no large-scale randomised studies comparing interventional to standard treatment have yet been conducted12. Currently, two main interventional strategies are under extensive investigation: (a) catheter-directed thrombolysis (CDT), and (b) mechanical thrombectomy. Each approach offers distinct advantages and disadvantages, potentially challenging the current standard of care, particularly in intermediate-high risk PE3. In these patients, CDT has shown some promising results regarding safety and efficacy, regardless of whether simple catheter-directed local thrombolysis or ultrasound-facilitated, catheter-directed thrombolysis (USCDT; EKOS [Boston Scientific]) is used4567. To date, no evidence suggests that one method is more effective than the other89. The industry-sponsored, randomised HI-PEITHO trial, with an adaptable design allowing for up to 544 participants, is currently underway. This trial is comparing USCDT to anticoagulation alone (the current standard of care) in a preselected group of patients with intermediate-high risk PE and is expected to provide much-needed robust clinical data10. In parallel, the investigator-initiated, non-industry-sponsored, academic RCT, titled “A Multicentre, Randomized Trial of Catheter-directed Thrombolysis in Intermediate-high Risk Acute Pulmonary Embolism (PRAGUE-26)” (ClinicalTrials.gov: NCT05493163), is now in progress. This trial will compare simple CDT (without ultrasound facilitation) to standard anticoagulation alone.