Clinical trial NCT04411316: Catheter-directed Thrombolysis Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis
Official title: Pharmacomechanical Catheter-directed Thrombolysis (PCDT) Plus Anticoagulation Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis:
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Deep Venous Thrombosis
Post Thrombotic Syndrome
Lead sponsor: University of Toledo
Sponsor class: OTHER
First posted: 2020-06-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Post-thrombotic syndrome (PTS) is a complication that can develop after deep vein thrombosis (DVT) of the lower extremities. PTS can occur at various times after the initial episode, but usually manifests within two years of initial DVT onset. Early and more complete thrombus clearance is believed by many to relieve venous outflow obstruction, preserve valvular function and reduce venous hypertension. Two previously published randomized controlled trials, the CAVENT trial and the ATTRACT trial, were larger and designed to investigate the efficacy of CDT. However, both of these trials included patients with iliofemoral as well as femoro-popliteal deep vein thrombosis. Our study will be limited to patients with iliofemoral deep vein thrombosis to assess whether Pharmacomechanical catheter-directed thrombolysis (PCDT) therapy utilizing AngioJet and tPA can safely and effectively reduce post thrombotic syndrome after 24 months.

Detailed description: Patients with Iliofemoral DVT are theoretically at the highest risk for development of PRS given involvement of the major drainage pathway of both superficial femoral and deep femoral veins. This would not only affect the primary venous drainage, but would also compromise the ability to develop efficient collateral pathways. This creates higher chances of developing post-thrombotic syndrome (PTS). The proposed trial would utilize Angiojet thrombectomy followed by catheter directed thrombolysis and Anticoagulation compared to Anticoagulation alone. To assess whether Pharmacomechanical catheter-directed thrombolysis (PCDT) therapy utilizing AngioJet and tPA for the treatment of iliofemoral deep venous thrombosis can safely and effectively reduce post thrombotic syndrome after 24 months.

Eligibility criteria: Inclusion Criteria:

1. Age\>18 and younger than 75
2. Symptomatic, proximal deep-vein thrombosis involving the Iliofemoral vein from 12/01/2019 to 12/01/2022

Exclusion Criteria:

1. Age less than 18 years or greater than 75 years.
2. Symptom duration \> 14 days for the DVT episode in the index leg (i.e. non-acute DVT).
3. In the index leg: established PTS, or previous symptomatic DVT within the last 2 years.
4. In the contralateral (non-index) leg: symptomatic acute DVT a) involving the popliteal and/or tibial veins; or b) for which thrombolysis is planned as part of initial therapy.
5. Limb-threatening circulatory compromise.
6. PE with hemodynamic compromise (i.e. hypotension).
7. Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness.
8. Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
9. Hemoglobin \< 9.0 mg/dl, INR \> 1.6 before warfarin was started, or platelets \< 100,000 /ml.
10. Moderate renal impairment in diabetic patients (estimated GFR \< 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR \< 30 ml/min).
11. Active bleeding, recent (\< 3 months) GI bleeding, severe liver dysfunction, bleeding diathesis.
12. Recent (\< 3 months) internal eye surgery or hemorrhagic retinopathy; recent (\< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure.
13. History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm.
14. Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: patients with non-melanoma primary skin cancers are eligible to participate in the study.
15. Severe hypertension on repeated readings (systolic \> 180mmHg or diastolic \> 105 mmHg).
16. Pregnant (positive pregnancy test, women of childbearing potential must be tested).
17. Recently (\< 2 years or chronic non-ambulatory status.
18. Use of a thienopryridine antiplatelet drug (except clopidogrel) in the last 5 days.
19. Life expectancy \< 2 years or chronic non-ambulatory status.
20. Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).

Primary outcomes:
measure: Post-thrombotic syndrome at any time between 6-month and 24-month.
timeFrame: 6-24 months
Secondary outcomes:
measure: Post-thrombotic syndrome at 6 months.
timeFrame: 6 months
measure: Post-thrombotic syndrome at 12 months.
timeFrame: 12 months
measure: Post-thrombotic syndrome at 18 months.
timeFrame: 18 months
measure: Post-thrombotic syndrome at 24 months.
timeFrame: 24 months
measure: Villalta scale at 6 months
timeFrame: 6 months
measure: Villalta scale at 12 months
timeFrame: 12 months
measure: Villalta scale at 18 months
timeFrame: 18 months
measure: Villalta scale at 24 months
timeFrame: 24 months
measure: Venous Clinical Severity Score at 6 months
timeFrame: 6 months
measure: Venous Clinical Severity Score at 12 months
timeFrame: 12 months
measure: Venous Clinical Severity Score at 18 months
timeFrame: 18 months
measure: Venous Clinical Severity Score at 24 months
timeFrame: 24 months
measure: Health-Related Quality of Life AT 6 months
timeFrame: 6 months
measure: Health-Related Quality of Life at 12 months.
timeFrame: 12 months
measure: Health-Related Quality of Life at 18 months.
timeFrame: 18 months
measure: Health-Related Quality of Life at 24 months.
timeFrame: 24 months
measure: Health-Related Quality of Life at 6 months.
timeFrame: 6 months
measure: Health-Related Quality of Life at 12 months.
timeFrame: 12 months
measure: Health-Related Quality of Life at 18 months.
timeFrame: 18 months
measure: Health-Related Quality of Life at 24 months.
timeFrame: 24 months
measure: Health-Related Quality of Life at 6 months.
timeFrame: 6 months
measure: Health-Related Quality of Life at 12 months.
timeFrame: 12 months
measure: Health-Related Quality of Life at 18 months.
timeFrame: 18 months
measure: Health-Related Quality of Life at 24 months.
timeFrame: 24 months
measure: Treatment Failures that are Not PTS.
timeFrame: 6-24 months
measure: Severity of presenting DVT Symptoms at 6 months
timeFrame: 6 months
measure: Severity of presenting DVT Symptoms at 12 months
timeFrame: 12 months
measure: Severity of presenting DVT Symptoms at 18 months
timeFrame: 18 months
measure: Severity of presenting DVT Symptoms at 24 months
timeFrame: 24 months
measure: Severity of presenting DVT Symptoms at 6 months
timeFrame: 6 months
measure: Severity of presenting DVT Symptoms at 12 months
timeFrame: 12 months
measure: Severity of presenting DVT Symptoms at 18 months
timeFrame: 18 months
measure: Severity of presenting DVT Symptoms at 24 months
timeFrame: 24 months
measure: Degree of Resolution of Thrombus with PCDT at 6 months.
timeFrame: 6 months
measure: Degree of Resolution of Thrombus with PCDT at 12 months.
timeFrame: 12 months
measure: Degree of Resolution of Thrombus with PCDT at 18 months.
timeFrame: 18 months
measure: Degree of Resolution of Thrombus with PCDT at 24 months.
timeFrame: 24 months
Other outcomes:
Locations:
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
Study officials:
affiliation: University of Toledo Health Science Campus
name: Ehab A Eltahawy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vedantham S. Valvular dysfunction and venous obstruction in the post-thrombotic syndrome. Thromb Res. 2009;123 Suppl 4:S62-5. doi: 10.1016/S0049-3848(09)70146-X.
citation: DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. Clinicaltrial.gov
citation: Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis. 2009 Nov;28(4):465-76. doi: 10.1007/s11239-009-0309-3. Epub 2009 Feb 18.
citation: 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.
citation: Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg NA, Gupta DK, Prandoni P, Vedantham S, Walsh ME, Weitz JI; American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014 Oct 28;130(18):1636-61. doi: 10.1161/CIR.0000000000000130. Epub 2014 Sep 22. No abstract available. Erratum In: Circulation. 2015 Feb 24;131(8):e359. doi: 10.1161/CIR.0000000000000185.
citation: Comerota AJ, Grewal N, Martinez JT, Chen JT, Disalle R, Andrews L, Sepanski D, Assi Z. Postthrombotic morbidity correlates with residual thrombus following catheter-directed thrombolysis for iliofemoral deep vein thrombosis. J Vasc Surg. 2012 Mar;55(3):768-73. doi: 10.1016/j.jvs.2011.10.032. Epub 2012 Jan 24.
citation: Schweizer J, Kirch W, Koch R, Elix H, Hellner G, Forkmann L, Graf A. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000 Oct;36(4):1336-43. doi: 10.1016/s0735-1097(00)00863-9.
citation: Goldhaber SZ, Buring JE, Lipnick RJ, Hennekens CH. Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Am J Med. 1984 Mar;76(3):393-7. doi: 10.1016/0002-9343(84)90656-9.
citation: Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg. 2002 Sep;24(3):209-14. doi: 10.1053/ejvs.2002.1665.
citation: Bashir R, Zack CJ, Zhao H, Comerota AJ, Bove AA. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone to treat lower-extremity proximal deep vein thrombosis. JAMA Intern Med. 2014 Sep;174(9):1494-501. doi: 10.1001/jamainternmed.2014.3415.
citation: Enden T, Haig Y, Klow NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012 Jan 7;379(9810):31-8. doi: 10.1016/S0140-6736(11)61753-4. Epub 2011 Dec 13.
citation: Haig Y, Enden T, Grotta O, Klow NE, Slagsvold CE, Ghanima W, Sandvik L, Hafsahl G, Holme PA, Holmen LO, Njaaastad AM, Sandbaek G, Sandset PM; CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016 Feb;3(2):e64-71. doi: 10.1016/S2352-3026(15)00248-3. Epub 2016 Jan 6.
citation: Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, Magnuson E, Razavi MK, Comerota AJ, Gornik HL, Murphy TP, Lewis L, Duncan JR, Nieters P, Derfler MC, Filion M, Gu CS, Kee S, Schneider J, Saad N, Blinder M, Moll S, Sacks D, Lin J, Rundback J, Garcia M, Razdan R, VanderWoude E, Marques V, Kearon C; ATTRACT Trial Investigators. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017 Dec 7;377(23):2240-2252. doi: 10.1056/NEJMoa1615066.