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

NCT01482273 | Completed

• 1 other identifier: 150/11
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Venous Thrombosis; Postthrombotic Syndrome

Keywords

catheter-directed thrombolysis; ilio-femoral deep vein thrombosis; Postthrombotic syndrome; Phlebographic scores; Phlebography; Catheters

Outcome Measures

Primary Outcomes (1)

• Improvement of Total EKOS Thrombus Score, a specifically developed venographic scoring system

  After 15 hours of CDT

Secondary Outcomes (5)

• Improvement of the "Venous Registry Index" venographic scoring system

  After 15 hours of CDT

• Early symptom relief assessed by standardized limb circumference measurements and validated visual analogue pain scale

  During and after 15 hours of CDT

• Treatment related complications

  30 days

• Development of PTS assessed by Villalta scale and Quality of life (CIVIQ)

  After 12 months

• Venous valve patency/insufficiency assessed by duplex sonography

  After 12 months

Study Arms (2)

CDT+US group

ACTIVE COMPARATOR

CDT using the EkoSonic Endovascular System with intravascular high-frequency, low-power ultrasound for 15 hours.

Procedure: CDT+US group

CDT-US group

ACTIVE COMPARATOR

CDT using the EkoSonic Endovascular System without intravascular high-frequency, low-power ultrasound for 15 hours.

Procedure: CDT-US group

Interventions

CDT-US group PROCEDURE

CDT using the EkoSonic Endovascular System without intravascular high-frequency, low-power ultrasound for 15 hours.

CDT-US group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

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

Bern, 3010, Switzerland

Location

Related Publications (13)

• Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830. doi: 10.1161/CIR.0b013e318214914f. Epub 2011 Mar 21.

  PMID: 21422387 BACKGROUND

• Siddiqi F, Odrljin TM, Fay PJ, Cox C, Francis CW. Binding of tissue-plasminogen activator to fibrin: effect of ultrasound. Blood. 1998 Mar 15;91(6):2019-25.

  PMID: 9490686 BACKGROUND

• Engelhardt TC, Taylor AJ, Simprini LA, Kucher N. Catheter-directed ultrasound-accelerated thrombolysis for the treatment of acute pulmonary embolism. Thromb Res. 2011 Aug;128(2):149-54. doi: 10.1016/j.thromres.2011.05.014. Epub 2011 Jun 8.

  PMID: 21641020 BACKGROUND

• Kahn SR, Shrier I, Julian JA, Ducruet T, Arsenault L, Miron MJ, Roussin A, Desmarais S, Joyal F, Kassis J, Solymoss S, Desjardins L, Lamping DL, Johri M, Ginsberg JS. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med. 2008 Nov 18;149(10):698-707. doi: 10.7326/0003-4819-149-10-200811180-00004.

  PMID: 19017588 RESULT

• Popuri RK, Vedantham S. The role of thrombolysis in the clinical management of deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):479-84. doi: 10.1161/ATVBAHA.110.213413.

  PMID: 21325669 RESULT

• Grewal NK, Martinez JT, Andrews L, Comerota AJ. Quantity of clot lysed after catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with postthrombotic morbidity. J Vasc Surg. 2010 May;51(5):1209-14. doi: 10.1016/j.jvs.2009.12.021. Epub 2010 Mar 27.

  PMID: 20347543 RESULT

• Grommes J, Strijkers R, Greiner A, Mahnken AH, Wittens CH. Safety and feasibility of ultrasound-accelerated catheter-directed thrombolysis in deep vein thrombosis. Eur J Vasc Endovasc Surg. 2011 Apr;41(4):526-32. doi: 10.1016/j.ejvs.2010.11.035. Epub 2011 Jan 21.

  PMID: 21256773 RESULT

• Hull RD, Marder VJ, Mah AF, Biel RK, Brant RF. Quantitative assessment of thrombus burden predicts the outcome of treatment for venous thrombosis: a systematic review. Am J Med. 2005 May;118(5):456-64. doi: 10.1016/j.amjmed.2005.01.025.

  PMID: 15866245 RESULT

• Sharifi M, Mehdipour M, Bay C, Smith G, Sharifi J. Endovenous therapy for deep venous thrombosis: the TORPEDO trial. Catheter Cardiovasc Interv. 2010 Sep 1;76(3):316-25. doi: 10.1002/ccd.22638.

  PMID: 20578224 RESULT

• Flumignan RL, Nakano LC, Flumignan CD, Baptista-Silva JC. Angioplasty or stenting for deep venous thrombosis. Cochrane Database Syst Rev. 2025 Feb 19;2(2):CD011468. doi: 10.1002/14651858.CD011468.pub2.

  PMID: 39968829 DERIVED

• Broderick C, Watson L, Armon MP. Thrombolytic strategies versus standard anticoagulation for acute deep vein thrombosis of the lower limb. Cochrane Database Syst Rev. 2021 Jan 19;1(1):CD002783. doi: 10.1002/14651858.CD002783.pub5.

  PMID: 33464575 DERIVED

• Engelberger RP, Stuck A, Spirk D, Willenberg T, Haine A, Periard D, Baumgartner I, Kucher N. Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis: 1-year follow-up data of a randomized-controlled trial. J Thromb Haemost. 2017 Jul;15(7):1351-1360. doi: 10.1111/jth.13709. Epub 2017 Jun 5.

  PMID: 28440041 DERIVED

• Engelberger RP, Spirk D, Willenberg T, Alatri A, Do DD, Baumgartner I, Kucher N. Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis. Circ Cardiovasc Interv. 2015 Jan;8(1):e002027. doi: 10.1161/CIRCINTERVENTIONS.114.002027.

  PMID: 25593121 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Postthrombotic Syndrome

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Venous Insufficiency

Study Officials

• Nils Kucher, MD

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

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: November 30, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2014
• Last Updated: July 17, 2015

Record last verified: 2015-07

Locations

CH (1)