ULTRAsound-assisted Catheter vs. STAndaRd Catheter Thrombolysis for Submassive Pulmonary Embolism

NCT03389971 | Completed

• 1 other identifier: UltraStar sPE
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Acute pulmonary embolism (PE) accounts for 5-10% of in-hospital deaths. Systemic anticoagulation (AC) is the standard of care and thrombolysis is recommended for those at a higher mortality risk. Catheter-directed therapies, mainly standard infusion catheter thrombolysis (CDT) and ultrasound-accelerated thrombolysis (USAT), have been introduced as new more effective and safer treatment modalities. USAT is a modification of standard catheter lysis utilizing a system of local ultrasound to dissociate the fibrin matrix of the thrombus with simultaneous acoustic streaming of the thrombolytic agent, allowing more efficient thrombolysis. However, there is limited comparative effectiveness data against standard multi-side hole catheter infusion. More rapid clearance of pulmonary thrombus by USAT compared to standard CDT may prove to be clinically beneficial and cost effective. Alternatively, if thrombus clearance is similar, the cost of USAT may exceed the cost of CDT (equipment and disposables), without realization any advantage.

Conditions

Submassive Pulmonary Embolism

Outcome Measures

Primary Outcomes (1)

• thrombus load reduction

  Determine differences in the percentage of thrombus load reduction from baseline to the termination of lysis between the two techniques

  12 months post surgery

Secondary Outcomes (12)

• cardiopulmonary and clinical outcomes - echocardiographic

  12 months post surgery

• cardiopulmonary and clinical outcomes - hemodynamic

  12 months post surgery

• cardiopulmonary and clinical outcomes - respiratory

  12 months post surgery

• cardiopulmonary and clinical outcomes - decompensation

  12 months post surgery

• cardiopulmonary and clinical outcomes - mortality

  12 months post surgery

Study Arms (2)

multi-sidehole catheter

ACTIVE COMPARATOR

Procedure: catheter-directed thrombolysis

USAT catheter

EXPERIMENTAL

Procedure: catheter-directed thrombolysis

Interventions

catheter-directed thrombolysis PROCEDURE

catheter-directed thrombolysis with commercially available multi-sidehole catheter or USAT catheter

USAT catheter; multi-sidehole catheter

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with submassive PE (CT or echocardiographic RV strain (defined as RV/LV ratio \>1) without persisting hypotension \<90mmHg or drop of systolic blood pressure by at least 40mm Hg for at least 15 minutes with signs of end-organ hypoperfusion (cold extremities or low urinary output \<30 mL/h or mental confusion) and without the need of catecholamine support or cardiopulmonary resuscitation)

You may not qualify if:

• \<18 or \>80
• pregnancy
• index PE symptom duration \>14 days
• high bleeding risk (any prior intracranial hemorrhage, known structural intracranial cerebrovascular disease or neoplasm, ischemic stroke within 3 months, suspected aortic dissection, active bleeding or bleeding diathesis, recent spinal or cranial/brain surgery, recent closed-head or facial trauma with bony fracture or brain injury)
• participation in any other investigational drug or device study
• life expectancy \<90 days
• inability to comply with study assessments

Sponsors & Collaborators

• Piedmont Healthcare: lead

Study Sites (1)

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

Location

Related Publications (41)

• Kahn SR, Houweling AH, Granton J, Rudski L, Dennie C, Hirsch A. Long-term outcomes after pulmonary embolism: current knowledge and future research. Blood Coagul Fibrinolysis. 2014 Jul;25(5):407-15. doi: 10.1097/MBC.0000000000000070.

  PMID: 24469387 BACKGROUND

• Avgerinos ED, Chaer RA. Catheter-directed interventions for acute pulmonary embolism. J Vasc Surg. 2015 Feb;61(2):559-65. doi: 10.1016/j.jvs.2014.10.036. Epub 2014 Dec 16.

  PMID: 25524824 BACKGROUND

• 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

• Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e419S-e496S. doi: 10.1378/chest.11-2301.

  PMID: 22315268 BACKGROUND

• Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk Noordegraaf A, Zamorano JL, Zompatori M; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014 Nov 14;35(43):3033-69, 3069a-3069k. doi: 10.1093/eurheartj/ehu283. Epub 2014 Aug 29. No abstract available.

  PMID: 25173341 BACKGROUND

• Becattini C, Agnelli G, Pesavento R, Silingardi M, Poggio R, Taliani MR, Ageno W. Incidence of chronic thromboembolic pulmonary hypertension after a first episode of pulmonary embolism. Chest. 2006 Jul;130(1):172-5. doi: 10.1378/chest.130.1.172.

  PMID: 16840398 BACKGROUND

• Meyer G, Planquette B, Sanchez O. Long-term outcome of pulmonary embolism. Curr Opin Hematol. 2008 Sep;15(5):499-503. doi: 10.1097/MOH.0b013e3283063a51.

  PMID: 18695374 BACKGROUND

• Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004 May 27;350(22):2257-64. doi: 10.1056/NEJMoa032274.

  PMID: 15163775 BACKGROUND

• Sanchez O, Trinquart L, Colombet I, Durieux P, Huisman MV, Chatellier G, Meyer G. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J. 2008 Jun;29(12):1569-77. doi: 10.1093/eurheartj/ehn208. Epub 2008 May 21.

  PMID: 18495689 BACKGROUND

• Guerin L, Couturaud F, Parent F, Revel MP, Gillaizeau F, Planquette B, Pontal D, Guegan M, Simonneau G, Meyer G, Sanchez O. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism. Thromb Haemost. 2014 Sep 2;112(3):598-605. doi: 10.1160/TH13-07-0538. Epub 2014 Jun 5.

  PMID: 24898545 BACKGROUND

• Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, Kumbhani DJ, Mukherjee D, Jaff MR, Giri J. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. doi: 10.1001/jama.2014.5990.

  PMID: 24938564 BACKGROUND

• Fasullo S, Scalzo S, Maringhini G, Ganci F, Cannizzaro S, Basile I, Cangemi D, Terrazzino G, Parrinello G, Sarullo FM, Baglini R, Paterna S, Di Pasquale P. Six-month echocardiographic study in patients with submassive pulmonary embolism and right ventricle dysfunction: comparison of thrombolysis with heparin. Am J Med Sci. 2011 Jan;341(1):33-9. doi: 10.1097/MAJ.0b013e3181f1fc3e.

  PMID: 20890176 BACKGROUND

• Kline JA, Steuerwald MT, Marchick MR, Hernandez-Nino J, Rose GA. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest. 2009 Nov;136(5):1202-1210. doi: 10.1378/chest.08-2988. Epub 2009 Jun 19.

  PMID: 19542256 BACKGROUND

• Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; "MOPETT" Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027. Epub 2012 Oct 24.

  PMID: 23102885 BACKGROUND

• Ain DL, Jaff MR. Treatment of Submassive Pulmonary Embolism: Knowing When to be Aggressive and When to be Conservative. Curr Treat Options Cardiovasc Med. 2015 Jun;17(6):385. doi: 10.1007/s11936-015-0385-y.

  PMID: 25895738 BACKGROUND

• Klok FA, Meyer G, Konstantinides S. Management of intermediate-risk pulmonary embolism: uncertainties and challenges. Eur J Haematol. 2015 Dec;95(6):489-97. doi: 10.1111/ejh.12612. Epub 2015 Jul 15.

  PMID: 26109174 BACKGROUND

• Weinberg I, Jaff MR. Treating large pulmonary emboli: do the guidelines guide us? Curr Opin Pulm Med. 2013 Sep;19(5):413-21. doi: 10.1097/MCP.0b013e3283642a63.

  PMID: 23884294 BACKGROUND

• Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.

  PMID: 24716681 BACKGROUND

• Engelberger RP, Kucher N. Ultrasound-assisted thrombolysis for acute pulmonary embolism: a systematic review. Eur Heart J. 2014 Mar;35(12):758-64. doi: 10.1093/eurheartj/ehu029. Epub 2014 Feb 3.

  PMID: 24497337 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

• Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.

  PMID: 24226805 BACKGROUND

• Kuo WT. Endovascular therapy for acute pulmonary embolism. J Vasc Interv Radiol. 2012 Feb;23(2):167-79.e4; quiz 179. doi: 10.1016/j.jvir.2011.10.012. Epub 2011 Dec 20.

  PMID: 22192633 BACKGROUND

• Kuo WT, Gould MK, Louie JD, Rosenberg JK, Sze DY, Hofmann LV. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol. 2009 Nov;20(11):1431-40. doi: 10.1016/j.jvir.2009.08.002.

  PMID: 19875060 BACKGROUND

• Weinberg I, Jaff MR. Accelerated thrombolysis for pulmonary embolism: will clinical benefit be ULTIMAtely realized? Circulation. 2014 Jan 28;129(4):420-1. doi: 10.1161/CIRCULATIONAHA.113.007132. Epub 2013 Nov 13. No abstract available.

  PMID: 24226804 BACKGROUND

• Bagla S, Smirniotopoulos JB, van Breda A, Sheridan MJ, Sterling KM. Ultrasound-accelerated catheter-directed thrombolysis for acute submassive pulmonary embolism. J Vasc Interv Radiol. 2015 Jul;26(7):1001-6. doi: 10.1016/j.jvir.2014.12.017. Epub 2015 Feb 18.

  PMID: 25704224 BACKGROUND

• George B, Wallace EL, Charnigo R, Wingerter KE, Kapadia P, Gurley JC, Smyth SS. A retrospective analysis of catheter-based thrombolytic therapy for acute submassive and massive pulmonary embolism. Vasc Med. 2015 Apr;20(2):122-30. doi: 10.1177/1358863X14568135.

  PMID: 25832600 BACKGROUND

• McCabe JM, Huang PH, Riedl L, Eisenhauer AC, Sobieszczyk P. Usefulness and safety of ultrasound-assisted catheter-directed thrombolysis for submassive pulmonary emboli. Am J Cardiol. 2015 Mar 15;115(6):821-4. doi: 10.1016/j.amjcard.2014.12.050. Epub 2015 Jan 7.

  PMID: 25633189 BACKGROUND

• Kuo WT, Banerjee A, Kim PS, DeMarco FJ Jr, Levy JR, Facchini FR, Unver K, Bertini MJ, Sista AK, Hall MJ, Rosenberg JK, De Gregorio MA. Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry. Chest. 2015 Sep;148(3):667-673. doi: 10.1378/chest.15-0119.

  PMID: 25856269 BACKGROUND

• Piazza G ET, Sterling KM, et al. A prospective, single-arm, multicenter trial of the ekosonic endovascular system with activase for acute pulmonary embolism (seattle II). American College of Cardiology 63rd Annual Scientific Meeting. 2014

  BACKGROUND

• Warntges S, Konstantinides SV. Progress in the management of acute pulmonary embolism. Curr Opin Pulm Med. 2015 Sep;21(5):417-24. doi: 10.1097/MCP.0000000000000196.

  PMID: 26186247 BACKGROUND

• Yu JN, Xue CY, Wang XG, Lin F, Liu CY, Lu FZ, Liu HL. 5-AZA-2'-deoxycytidine (5-AZA-CdR) leads to down-regulation of Dnmt1o and gene expression in preimplantation mouse embryos. Zygote. 2009 May;17(2):137-45. doi: 10.1017/S0967199408005169. Epub 2009 Feb 18.

  PMID: 19222872 BACKGROUND

• Liang NL, Avgerinos ED, Marone LK, Singh MJ, Makaroun MS, Chaer RA. Equivalent Outcomes Between Ultrasound-Assisted Thrombolysis and Standard Catheter-Directed Thrombolysis for the Treatment of Acute Pulmonary Embolism. J Vasc Surg Venous Lymphat Disord. 2015 Jan;3(1):120-1. doi: 10.1016/j.jvsv.2014.10.015. Epub 2014 Dec 15. No abstract available.

  PMID: 26993702 BACKGROUND

• Schrijver AM, van Leersum M, Fioole B, Reijnen MM, Hoksbergen AW, Vahl AC, de Vries JP. Dutch randomized trial comparing standard catheter-directed thrombolysis and ultrasound-accelerated thrombolysis for arterial thromboembolic infrainguinal disease (DUET). J Endovasc Ther. 2015 Feb;22(1):87-95. doi: 10.1177/1526602814566578.

  PMID: 25775686 BACKGROUND

• 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 BACKGROUND

• Qanadli SD, El Hajjam M, Vieillard-Baron A, Joseph T, Mesurolle B, Oliva VL, Barre O, Bruckert F, Dubourg O, Lacombe P. New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography. AJR Am J Roentgenol. 2001 Jun;176(6):1415-20. doi: 10.2214/ajr.176.6.1761415.

  PMID: 11373204 BACKGROUND

• Mastora I, Remy-Jardin M, Masson P, Galland E, Delannoy V, Bauchart JJ, Remy J. Severity of acute pulmonary embolism: evaluation of a new spiral CT angiographic score in correlation with echocardiographic data. Eur Radiol. 2003 Jan;13(1):29-35. doi: 10.1007/s00330-002-1515-y. Epub 2002 Jun 19.

  PMID: 12541107 BACKGROUND

• Gorkin L, Norvell NK, Rosen RC, Charles E, Shumaker SA, McIntyre KM, Capone RJ, Kostis J, Niaura R, Woods P, et al. Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy. Am J Cardiol. 1993 May 1;71(12):1069-73. doi: 10.1016/0002-9149(93)90575-w.

  PMID: 8475871 BACKGROUND

• ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.

  PMID: 12091180 BACKGROUND

• Kennedy RJ, Kenney HH, Dunfee BL. Thrombus resolution and hemodynamic recovery using ultrasound-accelerated thrombolysis in acute pulmonary embolism. J Vasc Interv Radiol. 2013 Jun;24(6):841-8. doi: 10.1016/j.jvir.2013.02.023. Epub 2013 Apr 16.

  PMID: 23601295 BACKGROUND

• Blinc A, Francis CW, Trudnowski JL, Carstensen EL. Characterization of ultrasound-potentiated fibrinolysis in vitro. Blood. 1993 May 15;81(10):2636-43.

  PMID: 8490172 BACKGROUND

• Francis CW, Blinc A, Lee S, Cox C. Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. Ultrasound Med Biol. 1995;21(3):419-24. doi: 10.1016/0301-5629(94)00119-x.

  PMID: 7645133 BACKGROUND

Study Officials

• Charles Ross, MD

  Piedmont Healthcare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2017
• First Posted: January 4, 2018
• Study Start: December 6, 2017
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: September 24, 2021

Record last verified: 2021-09

Locations

US (1)