Endovascular Therapy in Patients With Acute Deep Vein Thrombosis (LEVANTE)

April 23, 2023 updated by: Juraj Maďarič, MD, National Institute of Cardiovascular Diseases, Slovakia

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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:

  1. The occurrence of major bleeding and live-threatening bleeding episodes
  2. The development of PTS during the 6-month and 12-month follow-up period
  3. The rate of venous recanalization after intervention assessed by ultrasound
  4. The occurrence of pulmonary embolism
  5. Recurrence of DVT
  6. 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

Study Type

Observational

Enrollment (Actual)

110

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovakia
      • Banská Bystrica, Slovakia, 974 01
        • Central Slovakia Institute of Cardiovascular Diseases in Banská Bystrica
      • Bratislava, Slovakia, 833 48
        • National Institute of Cardiovascular Diseases, Slovakia
      • Košice, Slovakia, 04011
        • East Slovakia Institute of Cardiovascular Diseases in Košice

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients scheduled for endovascular treatment of extensive deep venous thrombosis (DVT)

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Thrombectomy plus local thrombolysis group
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
  • 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;
Local catheter directed thrombolysis alone group
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
- 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;

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-thrombotic syndrome
Time Frame: 24-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.
24-month follow-up period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The occurrence of major bleeding and live-threatening bleeding episodes
Time Frame: periprocedural, in-hospital (up to day 7), 24 months
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
Time Frame: 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
Time Frame: early - in-hospital (up to day 7), 6-month
assessed by ultrasound
early - in-hospital (up to day 7), 6-month
The occurrence of pulmonary embolism
Time Frame: early - in-hospital (up to day 7), 12-month, 24-month follow-up
clinical evaluation
early - in-hospital (up to day 7), 12-month, 24-month follow-up
Recurrence of DVT
Time Frame: 12-month, 24-month follow-up
clinical and ultrasound evaluation
12-month, 24-month follow-up
Mortality, MI, stroke during follow-up
Time Frame: In-hospital (up to day 7), 12-month, 24-month follow-up
history assessment
In-hospital (up to day 7), 12-month, 24-month follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Cardiovascular Diseases, Slovakia

Collaborators

East Slovakia Institute of Cardiovascular Diseases in Košice, Slovakia
Central Slovakia Institute of Cardiovascular Diseases in Banská Bystrica, Slovakia

Investigators

  • Principal Investigator: Juraj Maďarič, assoc. prof, National Institute of Cardiovascular Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2021

Primary Completion (Actual)

February 24, 2023

Study Completion (Actual)

February 24, 2023

Study Registration Dates

First Submitted

April 6, 2023

First Submitted That Met QC Criteria

April 21, 2023

First Posted (Actual)

April 24, 2023

Study Record Updates

Last Update Posted (Actual)

April 25, 2023

Last Update Submitted That Met QC Criteria

April 23, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 65176743 / LEVA002NUSCH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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