Ultrasound-enhanced Thrombolysis Versus Standard Catheter Directed Thrombolysis for Ilio-femoral Deep Vein Thrombosis (BERNUTIFUL)

July 16, 2015 updated by: University Hospital Inselspital, Berne

The BERN Ultrasound-enhanced Thrombolysis for Ilio-Femoral Deep Vein Thrombosis versUs Standard Catheter Directed thromboLysis Trial (BERNUTIFUL-Trial)

Patients with deep vein thrombosis (DVT) of the ilio-femoral veins have increased risk for developing post-thrombotic syndrome (PTS) and recurrent venous thromboembolism compared to more distal DVT. There's evidence that the early removal of the obstructing thrombus by catheter directed thrombolysis (CDT) 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 thromboembolism. A further development is ultrasound-enhanced thrombolysis combining CDT with a sophisticated catheter system that employs high-frequency, low-dose ultrasound. In vitro experiments showed that adding ultrasound to thrombolytic drugs accelerates thrombolysis while Ultrasound exposure alone results in no thrombolysis, however the superiority of ultrasound-enhanced thrombolysis over standard CDT has never been formally assessed in vivo. The hypothesis for this study is that ultrasound-enhanced thrombolysis reaches a higher degree of thrombolysis than standard CDT in patients with symptomatic ilio-femoral DVT.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 thromboembolism, and in the long term 20-40% of them develop a post-thrombotic syndrome (PTS). 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 thromboembolism. 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-dose 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.

Objective

To determine if the addition of intravascular high-frequency/low-dose ultrasound to standard CDT increases the percentage of clot lysis compared to CDT alone after treatment duration of 15 hours in patients with symptomatic ilio-femoral DVT and low bleeding risk

Methods

Study design: open-label (with blinding of 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.

Intervention: CDT using the EkoSonic Endovascular System with (CDT+US group) or without (CDT-US group) intravascular high-frequency, low-power ultrasound for 15 hours.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Not Applicable

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

  • Switzerland
      • Bern, Switzerland, 3010
        • Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern

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

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Symptomatic proximal DVT involving the iliac and/or common femoral vein, confirmed by Duplex Sonography, Angio-CT, Angio-MRI or Phlebography
  • Written informed consent

Exclusion Criteria

  • Age less than 18 years or greater than 75 years
  • Symptom duration > 14 days for the DVT episode in the index leg (i.e., non-acute DVT).
  • In the index leg: established post-thrombotic syndrome (PTS) or previous symptomatic DVT within the last 2 years.
  • Limb-threatening circulatory compromise.
  • PE with hemodynamic compromise (i.e., hypotension).
  • Inability to tolerate catheter procedure due to severe dyspnea or acute systemic illness.
  • Allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
  • Known significant bleeding risk, or known coagulation disorder (including vitamin K antagonists with INR > 2.0 and platelet count < 100 000/mm3)
  • Severe renal impairment (estimated GFR < 30 ml/min).
  • Active bleeding, recent (< 3 mo) GI bleeding, severe liver dysfunction, bleeding diathesis.
  • Recent (< 3 mo) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure.
  • History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm.
  • Severe hypertension on repeated readings (systolic > 180 mmHg or diastolic > 105 mmHg).
  • Pregnant, lactation or parturition within the previous 30 days (positive pregnancy test, women of childbearing age must be tested or use a medically accepted method of birth control).
  • Recently (< 1 mo) had thrombolysis.
  • Life expectancy < 6 months or chronic non-ambulatory status.
  • Participating in any other investigational drug or device study or previous enrollment in this study
  • Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).
  • Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CDT+US group
CDT using the EkoSonic Endovascular System with intravascular high-frequency, low-power ultrasound for 15 hours.
Procedure: CDT+US group
CDT using the EkoSonic Endovascular System with intravascular high-frequency, low-power ultrasound for 15 hours.
Active Comparator: CDT-US group
CDT using the EkoSonic Endovascular System without intravascular high-frequency, low-power ultrasound for 15 hours.
Procedure: CDT-US group
CDT using the EkoSonic Endovascular System without intravascular high-frequency, low-power ultrasound for 15 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Improvement of Total EKOS Thrombus Score, a specifically developed venographic scoring system
Time Frame: After 15 hours of CDT
After 15 hours of CDT

Secondary Outcome Measures

Outcome Measure
Time Frame
Improvement of the "Venous Registry Index" venographic scoring system
Time Frame: After 15 hours of CDT
After 15 hours of CDT
Early symptom relief assessed by standardized limb circumference measurements and validated visual analogue pain scale
Time Frame: During and after 15 hours of CDT
During and after 15 hours of CDT
Treatment related complications
Time Frame: 30 days
30 days
Development of PTS assessed by Villalta scale and Quality of life (CIVIQ)
Time Frame: After 12 months
After 12 months
Venous valve patency/insufficiency assessed by duplex sonography
Time Frame: After 12 months
After 12 months

Collaborators and Investigators

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

Sponsor

University Hospital Inselspital, Berne

Investigators

  • Principal Investigator: Nils Kucher, MD, Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern
  • Study Director: Torsten Willenberg, MD, Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern
  • Study Director: Iris Baumgartner, MD, Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern
  • Study Director: Rolf P Engelberger, MD, Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern

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

November 1, 2011

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

November 28, 2011

First Submitted That Met QC Criteria

November 29, 2011

First Posted (Estimate)

November 30, 2011

Study Record Updates

Last Update Posted (Estimate)

July 17, 2015

Last Update Submitted That Met QC Criteria

July 16, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 150/11

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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