Endovascular Therapy in Patients With Acute Deep Vein Thrombosis

Study Overview
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Brief Summary
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Despite optimal anticoagulation therapy of patients with proximal deep vein thrombosis (DVT), there is still high number of patients suffering from post-thrombotic syndrome (PTS) due to the chronic venous occlusion, suboptimal collateralization, and venous valvular dysfunction. Last two decades endovascular catheter-based treatment modalities have been tested and used in an attempt to reduce incidence and symptoms of PTS in selected patients. Especially, patients with extensive iliofemoral DVT have an increased risk of PTS. In an effort to accelerate thrombus dissolution or thrombus extraction, the endovascular removal of acute venous thrombus has been introduced as therapeutic option in patients with extensive iliofemoral DVT. Randomized trials of catheter-based strategies for thrombus removal have documented improved vein patency, preserved valves function, and reduced post-thrombotic syndrome. The aim of our study is to evaluate the safety and efficacy of different types of endovascular methods of treatment followed by anticoagulation therapy in patients with acute extensive DVT. Retrospective multicentre analysis of app 100 patients scheduled for endovascular treatment of extensive DVT. The results of mechanical/pharmacomechanical thrombectomy followed by local catheter directed thrombolysis (CDT), will be compared with CDT alone, or with ultrasound-accelerated thrombolysis. The 24-month incidence of PTS assessed by Villalta scoring system, major bleeding complications, the rate of venous recanalization, recurrence of DVT, and other end-points will be evaluated.

Detailed Description
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Aim: The aim of the study is to evaluate the long-term incidence of PTS in patients treated by different endovascular methods and protocols in combination with anticoagulation medication in patients with acute extensive DVT. Hypothesis: Mechanical / pharmacomechanical thrombectomy (PMT) following by CDT and further anticoagulation therapy is safe and effective mode of acute DVT treatment with reduction of PTS after 24 months in comparison with historical data and with other modes of endovascular therapy. Methods: Retrospective multicentre analysis of patients scheduled to interventional endovenous treatment of extensive DVT. The major end-point: 1. The development of PTS during the 24-month follow-up period The minor end-points: The occurrence of major bleeding and live-threatening bleeding episodes The development of PTS during the 6-month and 12-month follow-up period The rate of venous recanalization after intervention assessed by ultrasound The occurrence of pulmonary embolism Recurrence of DVT Mortality, myocardial infarction, stroke during follow-up The occurrence of PTS will be assessed by clinical evaluation and by Villalta scoring system. Patients suitable for endovascular therapy and for enrolment into study: first episode of acute iliofemoral DVT duration of symptoms <14 days symptomatic patients with no or limited response to initial anticoagulation therapy in terms of symptomatology and signs of recanalization low bleeding risk good functional capacity and life expectancy Endovascular procedures retrospectively analysed: Catheter directed thrombolysis (CDT): dedicated infusion catheter with side holes is placed across the acute thrombus, and slow, continuous infusion (through the catheter, or both through the catheter and sheath) of a chemical thrombolysis agent is initiated (alteplase 1mg per hour simultaneously with unfractionated heparine (UFH) in anticoagulation dosage); activated partial thromboplastin time (APTT), fibrinogen (Fbg), and blood count must be controlled; Mechanical thrombectomy: mechanical aspiration of fresh thrombus; mostly followed by CDT; Pharmacomechanical thrombectomy (PMT): combination of some form of mechanical disruption of the thrombus in conjunction with chemical lysis. There is evidence that PMT quickens thrombolysis compared with CDT alone. Dedicated devices combining chemical thrombolysis via power-pulse fluid plus plasminogen activator thrombus penetration, with rheolytic fluid-based disruption of thrombus and catheter-based aspiration thrombectomy. Ultrasound-accelerated thrombolysis combines chemical CDT with low-power high-frequency ultrasound application to the proprietary infusion catheter/wire combination, with the ultrasonic vibration purported to hasten thrombus disruption; the addition of ultrasound during lytic infusion increases the surface area of the fibrin, thereby permitting more efficient binding of the plasminogen activator to the fibrin-bound plasminogen Stenting of residual thrombotic lesions, and stenting of common iliac vein compression in the presence of May-Thurner syndrome; Peri-procedure and post-procedure care retrospectively analysed: continuous in-hospital monitoring to minimize CDT-related complications; APTT, Fbg concentration, and blood count are monitored; Anticoagulation after endovascular procedure as standard regimen, if no contraindications, mostly during the 6-month time period; longer anticoagulation regimen is at discretion of treated centre and physician; after venous stenting may be consider clopidogrel along with anticoagulation therapy for 1 month (not proven); Ultrasound evaluation during follow-up (data from documentation) recanalization - no residual thrombosis recanalization >50% recanalization <50% minimal US signs of recanalization/no recanalization Post-thrombotic syndrome: clinical evaluation and/or Villalta score No PTS: Villalta <5 points Mild: 5-9 points Moderate: 10-14 points Severe PTS: ≥15 points/venous ulcer

Official Title
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Long-term Effect of Different Modes of Endovascular Therapy in Combination With Anticoagulation Treatment in Patients With Acute Extensive Deep Vein Thrombosis (LEVANTE Research)

Conditions
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Acute Deep Venous Thrombosis

Intervention / Treatment
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* Device: Mechanical / pharmacomechanical thrombectomy plus local catheter directed thrombolysis
* Device: Local catheter directed thrombolysis alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: first episode of acute iliofemoral DVT duration of symptoms <14 days symptomatic patients with no or limited response to initial anticoagulation therapy in terms of symptomatology and signs of recanalization low bleeding risk good functional capacity and life expectancy Exclusion Criteria: - presence of malignity (2 centers out of 3) pregnancy haemorrhagic diathesis / high risk of bleeding negative prognosis of survival renal / hepatic failure chronic course of DVT

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Thrombectomy plus local thrombolysis group<br>Thrombectomy plus local thrombolysis group - patients treated by mechanical thrombectomy mostly followed by catheter directed thrombolysis (CDT), or by pharmaco-mechanical thrombectomy (PMT) - combination of some form of mechanical disruption of the thrombus in conjunction with chemical lysis. Thrombolysis by alteplase 1mg/hour. Procedure followed by anticoagulation therapy. | Device: Mechanical / pharmacomechanical thrombectomy plus local catheter directed thrombolysis<br>* Catheter directed thrombolysis (CDT): dedicated thrombolytic catheter with side holes is placed across the acute thrombus, and slow, continuous infusion (through the catheter, or both through the catheter and sheath) of a chemical thrombolysis agent is applied - alteplase 1mg/hour plus unfractionated heparine in anticoagulation dosage; Mechanical thrombectomy: mechanical aspiration of fresh thrombus; Pharmacomechanical thrombectomy (PMT): combination of mechanical disruption of the thrombus, and its aspiration, with simultaneous application of alteplase via dedicated catheter - instilation of acute/subacute thrombus with its subsequent aspiration;<br>|
| Local catheter directed thrombolysis alone group<br>Local catheter directed thrombolysis alone group - patients treated by dedicated catheter for local thrombolysis with side holes placed across the acute thrombus - continuous infusion of alteplase 1mg per hour simultaneously with unfractionated heparine in anticoagulation dosage. Without mechanical or pharmaco-mechanical thrombectomy. Procedure followed by anticoagulation therapy. | Device: Local catheter directed thrombolysis alone<br>* - Catheter directed thrombolysis (CDT): dedicated thrombolytic catheter with side holes is placed across the acute thrombus, and slow, continuous infusion (through the catheter, or both through the catheter and sheath) of a chemical thrombolysis agent is applied - alteplase 1mg/hour plus unfractionated heparine in anticoagulation dosage;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-thrombotic syndrome | The occurrence of PTS will be assessed by clinical evaluation and by Villalta scoring system (0-33), higher scores mean a worse outcome. | 24-month follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of major bleeding and live-threatening bleeding episodes | clinical and laboratory evaluation of bleeding | periprocedural, in-hospital (up to day 7), 24 months | 
| The development of PTS during the 6-month and 12-month follow-up period | The occurrence of PTS will be assessed by clinical evaluation and by Villalta scoring system (0-33), higher scores mean a worse outcome. | 6-month and 12-month follow-up period | 
| The rate of venous recanalization after intervention | assessed by ultrasound | early - in-hospital (up to day 7), 6-month | 
| The occurrence of pulmonary embolism | clinical evaluation | early - in-hospital (up to day 7), 12-month, 24-month follow-up | 
| Recurrence of DVT | clinical and ultrasound evaluation | 12-month, 24-month follow-up | 
| Mortality, MI, stroke during follow-up | history assessment | In-hospital (up to day 7), 12-month, 24-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deep venous thrombosis, endovascular thrombectomy, anticoagulation