RecruitingPhase 4NCT05493163

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

A Multicentre, Randomized Trial of Catheter-directed Thrombolysis in Intermediate-high Risk Acute Pulmonary Embolism (PRAGUE-26)

Sponsor

Faculty Hospital Kralovske Vinohrady

Enrollment

558 participants

Start Date

Oct 19, 2022

Study Type

INTERVENTIONAL

Conditions

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.

Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria4

Age > 18 years and not over 80 years.
Computed tomography angiography (CTA)-verified proximal* PE AND symptom onset < 14 days prior.
Intermediate-high risk PE with a SPESI score ≥ 1 AND RV dysfunction** AND an elevated biomarker *** (hs-troponin or NT-proBNP) level.
Signed informed consent.

Exclusion Criteria13

Active clinically significant bleeding.
Any haemorrhagic stroke OR a recent (< 6 months) ischaemic stroke/transient ischaemic attack.
Recent (< 3 months) cranial trauma OR another active intracranial/intraspinal process.
Major surgery within 7 days prior.
Active malignancy OR other severe illness with expected survival < 2 years.
Haemoglobin level < 80 g/L; international normalised ratio > 2.0, platelet count ≤ 100 x 109; creatinine level > 200 µmol/L.
Pregnant or breastfeeding, fertility without previous exclusion of gravidity.
Allergic to thrombolytics or heparin or low-molecular-weight heparin (LMWH), contrast allergy, a history of heparin-induced thrombocytopenia.
Floating thrombi in transit through a patent foramen ovale.
Participation in another clinical trial.
A perfusion defect in at least one main or one lobar pulmonary artery is evident on CTA.
RV/LV ratio ≥ 0.9 on transthoracic echocardiography or CTA. *** hs-troponin I (TnI) > 53 ng/L (men) or > 34 ng/L (women); NT-proBNP level > 600 pg/mL.
SPESI - Simplified Pulmonary Embolism Severity Index.