Evaluation of the Standard Catheter-directed Thrombolysis Effectiveness in Intermediate-High-Risk Pulmonary Embolism Patients (ESCADlys-PE)

Evaluation of the Standard Catheter-directed Thrombolysis (SCDT) Effectiveness in Intermediate-High-Risk Pulmonary Embolism Patients

A single-center, open-label, randomized comparative study of two treatment strategies in patients with intermediate-high-risk acute pulmonary embolism (PE). Patients will be randomized in a 1:1 ratio to standard anticoagulant therapy or standard catheter-directed thrombolysis (SСDT) with a low dose of alteplase, followed by evaluation of short- and long-term efficacy and safety in each group

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Embolism Acute
• Intervention / Treatment: Combination product: Standard Catheter-Directed Low Dose Thrombolysis; Drug: Standard Anticoagulation

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olga Moiseeva; Phone Number: +79213068249; Email: moiseeva_om@almazovcentre.ru
• Study Contact Backup: Name: Maria Simakova; Phone Number: +79215898763; Email: simakova_ma@almazovcentre.ru

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197341
    • Recruiting
    • Almazov National Medical Research Centre
    • Contact: Alexandra Konradi, MD, PhD; Phone Number: 005103 007(812)7023749; Email: ahleague@mail.ru
    • Contact: Svetlana Villevalde, MD, PhD; Email: villevaldes@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years
• Computed tomography angiography (CTA) - verified proximal (pulmonary trunk and/or main and/or lobar branches of the pulmonary artery) PE and symptom onset < 14 days prior
• Intermediate-high risk PE with a RV dysfunction (RV/LV diameter ratio >1 on TTE or CTA) and an elevated biomarker (hs-troponin or NT-proBNP) level
• Signed informed consent

Exclusion Criteria:

• High-risk pulmonary embolism
• Thrombus in the heart chambers on TTE
• Absolute contraindications for the use of thrombolytic therapy: history of hemorrhagic stroke or stroke of unknown etiology; ischemic stroke or transient ischemic attack within the last 6 months; extensive bleeding currently or within the previous 6 months, hemorrhagic diathesis; diseases of the central nervous system (including neoplasms, aneurysm, surgery on the brain or spinal cord); intracranial (including subarachnoid) hemorrhage currently or in history, suspicion of hemorrhagic stroke; severe uncontrolled arterial hypertension; major surgery or major trauma within the previous 3 months, recent traumatic brain injury; labor during the previous 10 days; severe liver diseases, including liver failure, cirrhosis, portal hypertension (including esophageal varices) and active hepatitis; bacterial endocarditis, pericarditis; acute pancreatitis; confirmed peptic ulcer of the stomach or duodenum within the last 3 months; arterial aneurysms, congenital anomalies of arteries/veins;
• Haemoglobin level < 70 g/L, platelet count ≤ 100 x 109
• Allergic to alteplase or UFH or contrast allergy
• Pregnant or breastfeeding
• Clinically significant malignancies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Catheter-Directed Thrombolysis; Local, standard catheter-directed thrombolysis with a total alteplase dose of 10 mg (for unilateral lesion) or 20 mg (for bilateral lesion) administered over 9 hours	Combination product: Standard Catheter-Directed Low Dose Thrombolysis; Using femoral or jugular vein access the mechanical blood clots fragmentation by PigTail 6F catheter circular rotational movements. For unilateral thromboembolism, the PigTail catheter is positioned in the obstructed branch of the pulmonary artery, 1 mg of alteplase is injected as a bolus, followed by a micro-jet injection of 1 mg/hour. For bilateral thromboembolism, the PigTail catheter is positioned in the pulmonary trunk with a bolus of 2 mg alteplase followed by an infusion of 2 mg/hour. The total duration of infusion will be 9 hours, the total dose of alteplase will be 10 mg for unilateral lesions and 20 mg for bilateral lesions. During the alteplase infusion, unfractionated heparin is continued with a target activated partial thromboplastin time (aPTT) of 50 to 60 seconds. After completion of the procedure, UFH therapy is continued for 24 hours, followed by a change to oral anticoagulants.
Active Comparator: Standard Anticoagulation; Therapy with UFH with targeted аPTT lasts for 24 hours (no more than 48 hours in total). Then the change to oral anticoagulants is performed.	Drug: Standard Anticoagulation; Therapy with UFH with targeted аPTT lasts for 24 hours (no more than 48 hours in total). Then the change to oral anticoagulants is performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A decrease in the ratio of RV/LV diameters	A decrease in the ratio of RV/LV diameters by 20% or more from the initial value 48 ± 6 hours after initiation of therapy	48 ± 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality	90 days
Cardiorespiratory decompensation or collapse	necessity of inotropic and vasopressor support; cardiac arrest or need for CPR; obstructive shock, placement on extracorporeal membrane oxygenation (ECMO), intubation, or initiation of non-invasive mechanical ventilation	7 days
Major bleeding events	International Society on Thrombosis and Hemostasis (ISTH) major bleeding	7 days
PE thrombus load reduction	Qanadli score by CT-scan	48 hours
The degree of residual pulmonary artery thrombosis with perfusion deficiency	The degree of residual pulmonary artery thrombosis with perfusion deficiency by CT-scan	180 days
Post-pulmonary embolism syndrome formation	The presence of symptomatic pulmonary artery residual thrombosis	180 days

Collaborators and Investigators

• Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Publications and helpful links

General Publications

• Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ni Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 27, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: anticoagulant therapy; acute pulmonary embolism; catheter-directed thrombolysis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 1511-23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No