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The BERN Ultrasound-enhanced Thrombolysis for Ilio-Femoral deep vein thrombosis versUs standard catheter directed thromboLysis trial

Applicant Kucher Nils
Number 140804
Funding scheme Project funding (Div. I-III)
Research institution Klinik und Poliklinik für Angiologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Clinical Cardiovascular Research
Start/End 01.05.2012 - 31.10.2014
Approved amount 191'360.00
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Keywords (4)

post-thrombotic syndrome; deep vein thrombosis; catheter-directed thrombolysis; ultrasound-enhanced thrombolysis

Lay Summary (German)

Lead
Lay summary
Tiefe Venenthrombosen (TVT) sind ein sehr häufiges Krankheitsbild mit einer jährlichen Inzidenz in der Allgemeinbevölkerung von knapp 1 Fall pro 1000 Personen. Auf längere Zeit gesehen besteht nach einer TVT vor allem das Risiko eines post-thrombotischen Syndroms (PTS). Als PTS bezeichnet man alle chronischen Symptome und klinischen Zeichen, die nach einer Thrombose der tiefen Bein- und Beckenvenen entstehen. Das klinische Spektrum reicht von Beinschmerzen, Schwellungen bis zu offenen Beinen (Ulcus cruris venosum) und Invalidität der betroffenen Personen. Die Standardbehandlung ist die Kompressionsbehandlung und Gabe von blutverdünnenden Medikamenten, welche jedoch selten zur Auflösung des Blutgerinnsels beiträgt. Bei schweren Thrombosen wird deshalb eine lokale medikamentöse Auflösungsbehandlung des Blutgerinnsels mit einem Kathetereingriff durchgeführt. Die Verabreichung von Ultraschallenergie beschleuinigt die medikamentöse Auflösung von Blutgerinnseln in vitro. Vorteile einer solchen Behandlung wäre eine Reduktion des PTS sowie verbesserte Sicherheit bei tieferen Dosierungen der Auflösungsmedikamente. Ziel dieser randomisierten Studie ist es zu untersuchen, ob die Ultraschall-verstärkte medikamentöse Auflösungsbehandlung m Vergleich zur standardisierten medikamentösen Auflösungsbehandlung bei Patienten mit schwerer Beckenvenenthrombose eine vermehrte Auflösung des Blutgerinnsel herbeiführt, ohne dabei das Komplikationsrisiko zu erhöhen.
Direct link to Lay Summary Last update: 21.02.2013

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Publication
Ultrasound-Assisted Versus Conventional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis
Engelberger Rolf P, Ultrasound-Assisted Versus Conventional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis, in Circulation Cardiovascular Intervention, 8.

Abstract

1. SUMMARY1.1 Background: Deep vein thrombosis (DVT) is a public health problem with an annual incidence of 1 per 1000. Besides the acute risk of potentially fatal pulmonary embolism or phlegmasia cerulea dolens, these patients are at increased risk of recurrent venous thrombo-embolism, and in the long term 20-40% of them develop a post-thrombotic syndrome (PTS), defined as chronic venous symptoms and/or signs secondary to deep vein thrombosis. PTS mainly develops in patients with DVT affecting the ilio-femoral veins, adversely affects the quality of life and causes important health care costs to the society. There’s evidence that the early removal of the obstructing thrombus reduces the risk of developing a PTS, and a higher degree of thrombolysis is associated with lower incidence of PTS, better quality of life and lower risk of recurrent venous thrombo-embolism. Therefore, in addition to standard anticoagulation therapy, the latest international guidelines recommend catheter-directed thrombolysis (CDT) as first-line treatment for patients with ilio-femoral DVT and low bleeding risk. CDT refers to the infusion of thrombolytic drugs directly into the thrombus via a multisidehole catheter which is embedded in the thrombus using imaging guidance. A further development is ultrasound-enhanced thrombolysis combining CDT with a sophisticated catheter system that employs high-frequency, low-power ultrasound. In vitro experiments showed that adding Ultrasound to thrombolytic drugs accelerates thrombolysis while Ultrasound exposure alone results in no thrombolysis. Although ultrasound-enhanced thrombolysis is now widely used to treat ilio-femoral DVT or high-risk pulmonary embolism, it is currently not known if this technique is superior to standard CDT. 1.2 Hypothesis/Aims of the projectHypothesis: The addition of high-energy, low-power ultrasound to standard CDT improves the resolution of ilio-femoral DVT without increasing the risk of bleeding complications. Aims: 1) Primary Objective: to determine if the addition of intravascular high-frequency/low-dose ultrasound to standard CDT increases the percentage of clot removal compared to CDT alone after a treatment duration of 15 hours. 2) Secondary Objectives: a) to evaluate procedure related bleeding complications; b) to evaluate improvement of symptoms and signs after 24 hours; c) to determine disease specific quality of life and incidence and severity of PTS and at 3, 6 and 12 months; d) Evaluate venous patency at 3, 6 and 12 months. 1.3 Methods: Study design: open-label (with blinding of imaging data-analyzing physicians), randomized, controlled, single center clinical trial with a follow-up period of 12 months. Subjects: total of 20 patients (10 in each study group) of 18-75 years of age with acute, symptomatic, objectively confirmed ilio-femoral DVT and a low bleeding risk are recruited at the University Hospital Bern. Intervention: CDT using the EkoSonic Endovascular System with (intervention group) or without (control group) intravascular high-frequency, low-power ultrasound for 15 hours. Outcome assessments: a) Short-term outcomes: 1) improvement of Total EKOS Thrombus Score, a specifically developed venographic scoring system, and the Venous Registry Index” venographic scoring system after 15 hours of CDT and 2) Early symptom relief assessed by standardized limb circumference measurements and validated visual analogue pain scale; 3) standardized reporting of bleeding complications; b) Long-term outcomes at 3, 6, and 12 months follow-up visits: 3) Development of PTS assessed by Villalta scale, chronic venous insufficiency assessed by revised Venous Clinical Severity Score and CEAP and disease specific quality of life (CIVIQ); 4) Venous valve competence assessed by duplexsonography.1.4 Potential impact of this project: First, this study gives the unique opportunity to study in vivo the effect of high-frequency, low-power ultrasound in addition to standard CDT for the treatment of DVT. Because of the strong correlation between the degree of clot removal and long-term outcome, this study potentially may have an important impact on future treatment strategies for patients with symptomatic ilio-femoral DVT, and possibly also for treatment of thrombotic diseases in other vascular beds. Second, the sophisticated catheter system for ultrasound-enhanced thrombolysis is substantially more expensive than standard CDT, therefore its use should needs to be justified by scientific evidence based on a clinical trial.
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