Ultrasound-enhanced Thrombolysis Versus Standard Catheter Directed Thrombolysis for Ilio-femoral Deep Vein Thrombosis (BERNUTIFUL)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention |
|---|---|
|
Venous Thrombosis Postthrombotic Syndrome |
Procedure: CDT+US group Procedure: CDT-US group |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | The BERN Ultrasound-enhanced Thrombolysis for Ilio-Femoral Deep Vein Thrombosis versUs Standard Catheter Directed thromboLysis Trial (BERNUTIFUL-Trial) |
- Improvement of Total EKOS Thrombus Score, a specifically developed venographic scoring system [ Time Frame: After 15 hours of CDT ] [ Designated as safety issue: No ]
- Improvement of the "Venous Registry Index" venographic scoring system [ Time Frame: After 15 hours of CDT ] [ Designated as safety issue: No ]
- Early symptom relief assessed by standardized limb circumference measurements and validated visual analogue pain scale [ Time Frame: During and after 15 hours of CDT ] [ Designated as safety issue: No ]
- Treatment related complications [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
- Development of PTS assessed by Villalta scale and Quality of life (CIVIQ) [ Time Frame: After 12 months ] [ Designated as safety issue: No ]
- Venous valve patency/insufficiency assessed by duplex sonography [ Time Frame: After 12 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 48 |
| Study Start Date: | November 2011 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Nils Kucher, MD | +41 31 632 7963 | nils.kucher@insel.ch |
| Contact: Rolf P Engelberger, MD | +41 31 632 11 11 | rolf.engelberger@insel.ch |
| Switzerland | |
| Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern | Recruiting |
| Bern, Switzerland, 3010 | |
| Principal Investigator: Nils Kucher, MD | |
| Sub-Investigator: Rolf P Engelberger, MD | |
| 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 |
More Information
Publications:
| Responsible Party: | Nils Kucher, Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital and University of Bern |
| ClinicalTrials.gov Identifier: | NCT01482273 History of Changes |
| Other Study ID Numbers: | 150/11 |
| Study First Received: | November 28, 2011 |
| Last Updated: | January 7, 2013 |
| Health Authority: | Switzerland: Independent Local Research Ethic Commission (Ethikkommission) |
Keywords provided by University Hospital Inselspital, Berne:
|
catheter-directed thrombolysis ilio-femoral deep vein thrombosis Postthrombotic syndrome |
Phlebographic scores Phlebography Catheters |
Additional relevant MeSH terms:
|
Postthrombotic Syndrome Postphlebitic Syndrome Thrombosis Venous Thrombosis Venous Thromboembolism Embolism and Thrombosis |
Vascular Diseases Cardiovascular Diseases Venous Insufficiency Phlebitis Peripheral Vascular Diseases Thromboembolism |
ClinicalTrials.gov processed this record on May 23, 2013