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

Summary

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.

Conditions

• Pulmonary Embolism

Interventions

DRUG

Thrombolytic

Local, catheter-directed thrombolysis with a total dose of 10mg per affected lung administered over 9 hours.

DRUG

Standard anticoagulation

Standard anticoagulation therapy of acute pulmonary embolism.

Sponsors & Collaborators

• Charles University

  collaborator UNKNOWN

• University Hospital Ostrava

  collaborator OTHER

• University Hospital Olomouc

  collaborator OTHER

• University Hospital Brno

  collaborator UNKNOWN

• St. Anne´s University Hospital Brno

  collaborator UNKNOWN

• General University Hospital, Prague

  collaborator OTHER

• University Hospital Pilsen

  collaborator OTHER

• Pardubice Hospital

  collaborator UNKNOWN

• Faculty Hospital Kralovske Vinohrady

  lead OTHER_GOV

Principal Investigators

• Viktor Kocka, MD, PhD · Deputy Head of Department of Cardiology

• Josef Kroupa, MD, PhD · Interventional Cardiologist

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-10-19

Primary Completion

2026-01-31

Completion

2028-01-31

Countries

• Czechia

Study Locations