Catheter-directed Thrombolysis Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis

NCT04411316 | Withdrawn Phase 4 FDA Drug FDA Device

• 1 other identifier: 300439
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Deep Venous Thrombosis; Post Thrombotic Syndrome

Outcome Measures

Primary Outcomes (1)

• Post-thrombotic syndrome at any time between 6-month and 24-month.

  Occurrence of post-thrombotic syndrome at any time between 6-month and 24-month after procedure by Villata score (Villata score \>5 or more), or if patient underwent an unplanned endovascular procedure to treat venous symptoms. The variables in villata scores are pain, cramps, heaviness, parasthesia, pruritus, pretibial edema, skin induration, hyperpigmentation, pain during calf compression, venous ectasia and redness. The Villata score ranges 0-45. Villata score \<5 means no post-thrombotic syndrome. Villata score 5-9 mild post-thrombotic syndrome. Villata score 10-14 means moderate post-thrombotic syndrome. Villata score ≥15 or presence of an ulcer indicates severe post-thrombotic syndrome. The more is the score the worse is the disease.

  6-24 months

Secondary Outcomes (37)

• Post-thrombotic syndrome at 6 months.

  6 months

• Post-thrombotic syndrome at 12 months.

  12 months

• Post-thrombotic syndrome at 18 months.

  18 months

• Post-thrombotic syndrome at 24 months.

  24 months

• Villalta scale at 6 months

  6 months

Study Arms (2)

Pharmacomechanical thrombolysis plus anticoagulation

EXPERIMENTAL

This group of patients will receive Pharmacomechanical catheter-directed thrombolysis (PCDT) plus Anticoagulation. PCDT will be AngioJet along with alteplase. Anticoagulation will be heparin only

Combination Product: Catheter directed thrombolysis plus anticoagulation

Anticoagulation

ACTIVE COMPARATOR

This group of patients will receive standard anticoagulation only. Anticoagulation will be Heparin only

Drug: Anticoagulation

Interventions

Catheter directed thrombolysis plus anticoagulation COMBINATION_PRODUCT

Patients will be randomized to pharmacomechanical catheter directed thrombolysis plus anticoagulation. PCDT will be AngioJet along with alteplase.

Also known as: Pharmacomechanical thrombolysis

Pharmacomechanical thrombolysis plus anticoagulation

Anticoagulation DRUG

Patients will receive anticoagulation alone. Anticoagulation will be heparin only.

Anticoagulation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

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 PTS, or previous symptomatic DVT within the last 2 years.
• 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.
• Limb-threatening circulatory compromise.
• PE with hemodynamic compromise (i.e. hypotension).
• Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness.
• 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.
• Hemoglobin \< 9.0 mg/dl, INR \> 1.6 before warfarin was started, or platelets \< 100,000 /ml.
• Moderate renal impairment in diabetic patients (estimated GFR \< 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR \< 30 ml/min).
• Active bleeding, recent (\< 3 months) GI bleeding, severe liver dysfunction, bleeding diathesis.
• Recent (\< 3 months) 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.
• 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.
• Severe hypertension on repeated readings (systolic \> 180mmHg or diastolic \> 105 mmHg).

Sponsors & Collaborators

• University of Toledo Health Science Campus: lead

Study Sites (1)

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Related Publications (13)

• 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.

  PMID: 19303507 BACKGROUND

• DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. Clinicaltrial.gov

  BACKGROUND

• 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.

  PMID: 19224134 RESULT

• 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

• 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.

  PMID: 25246013 RESULT

• 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.

  PMID: 22277690 RESULT

• 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.

  PMID: 11028492 RESULT

• 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.

  PMID: 6367454 RESULT

• 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.

  PMID: 12217281 RESULT

• 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.

  PMID: 25047081 RESULT

• 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.

  PMID: 22172244 RESULT

• 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.

  PMID: 26853645 RESULT

• 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.

  PMID: 29211671 RESULT

Related Links

• DUTCH CAVA-trial: CAtheter Versus Anticoagulation Alone for Acute Primary (Ilio)Femoral DVT. (NL28394)

MeSH Terms

Conditions

Venous Thrombosis; Postthrombotic Syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• Ehab A Eltahawy, MD

  University of Toledo Health Science Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of Medicine

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: June 2, 2020
• Study Start: December 19, 2019
• Primary Completion: December 19, 2022
• Study Completion: December 19, 2022
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)