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

Deep Venous Thrombosis Clinical Trial

Official title:

Pharmacomechanical Catheter-directed Thrombolysis (PCDT) Plus Anticoagulation Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis:

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04411316
• Other study ID #: 300439
• Status: Withdrawn
• Phase: Phase 4
• Start date: December 19, 2019
• Est. completion date: December 19, 2022

Study information

• Verified date: September 2021
• Source: University of Toledo Health Science Campus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 19, 2022
• Est. primary completion date: December 19, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Deep Venous Thrombosis
• Post Thrombotic Syndrome
• Postphlebitic Syndrome
• Postthrombotic Syndrome
• Thrombosis
• Venous Thrombosis

Intervention

Combination Product:
• Catheter directed thrombolysis plus anticoagulation
Patients will be randomized to pharmacomechanical catheter directed thrombolysis plus anticoagulation. PCDT will be AngioJet along with alteplase.

Drug:
• Anticoagulation
Patients will receive anticoagulation alone. Anticoagulation will be heparin only.

Locations

Country	Name	City	State
United States	University of Toledo Medical Center	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University of Toledo Health Science Campus

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. Review. — View 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: 1 — View 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):76 — View Citation

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

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. — View Citation

Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbæk G, Sandset PM; CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute ili — View 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. — View Citation

Haig Y, Enden T, Grøtta O, Kløw NE, Slagsvold CE, Ghanima W, Sandvik L, Hafsahl G, Holme PA, Holmen LO, Njaaastad AM, Sandbæk G, Sandset PM; CaVenT Study Group. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT — View 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 — View 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 thro — View 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. — View 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 — View 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. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Post-thrombotic syndrome at 6 months.	Occurrence of post-thrombotic syndrome at 6 months measured by Villata score (Villalta score was 5 or higher).	6 months
Secondary	Post-thrombotic syndrome at 12 months.	Occurrence of post-thrombotic syndrome at 12 months measured by Villata score (Villalta score was 5 or higher).	12 months
Secondary	Post-thrombotic syndrome at 18 months.	Occurrence of post-thrombotic syndrome at 18 months measured by Villata score (Villalta score was 5 or higher).	18 months
Secondary	Post-thrombotic syndrome at 24 months.	Occurrence of post-thrombotic syndrome at 24 months measured by Villata score (Villalta score was 5 or higher).	24 months
Secondary	Villalta scale at 6 months	The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Villalta scale	6 months
Secondary	Villalta scale at 12 months	The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Villalta scale.	12 months
Secondary	Villalta scale at 18 months	The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale.	18 months
Secondary	Villalta scale at 24 months	The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale.	24 months
Secondary	Venous Clinical Severity Score at 6 months	The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Venous Clinical Severity Score.	6 months
Secondary	Venous Clinical Severity Score at 12 months	The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Venous Clinical Severity Score.	12 months
Secondary	Venous Clinical Severity Score at 18 months	The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Venous Clinical Severity Score.	18 months
Secondary	Venous Clinical Severity Score at 24 months	The severity of the post-thrombotic syndrome to be evaluated at 24 months with the use of the Venous Clinical Severity Score.	24 months
Secondary	Health-Related Quality of Life AT 6 months	Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life	6 months
Secondary	Health-Related Quality of Life at 12 months.	Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 12 months.	12 months
Secondary	Health-Related Quality of Life at 18 months.	Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 18 months.	18 months
Secondary	Health-Related Quality of Life at 24 months.	Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 24 months.	24 months
Secondary	Health-Related Quality of Life at 6 months.	Health-Related Quality of Life measured by Generic Quality of Life at 6 months.	6 months
Secondary	Health-Related Quality of Life at 12 months.	Health-Related Quality of Life measured by Generic Quality of Life at 12 months	12 months
Secondary	Health-Related Quality of Life at 18 months.	Health-Related Quality of Life measured by Generic Quality of Life at 18 months.	18 months
Secondary	Health-Related Quality of Life at 24 months.	Health-Related Quality of Life measured by Generic Quality of Life at 24 months.	24 months
Secondary	Health-Related Quality of Life at 6 months.	Health-Related Quality of Life measured by Administration of QOL Measures at 6 months.	6 months
Secondary	Health-Related Quality of Life at 12 months.	Health-Related Quality of Life measured by Administration of QOL Measures at 12 months.	12 months
Secondary	Health-Related Quality of Life at 18 months.	Health-Related Quality of Life measured by Administration of QOL Measures at 18 months.	18 months
Secondary	Health-Related Quality of Life at 24 months.	Health-Related Quality of Life measured by Administration of QOL Measures at 24 months.	24 months
Secondary	Treatment Failures that are Not PTS.	Treatment Failures that are Not PTS (defined as one or more of the following during the 24 months post randomization: 1) the patient underwent an unplanned endovascular or surgical intervention for the treatment of severe symptomatic venous disease in the index leg within the first 24 months after randomization (2) the subject underwent an amputation in the index leg anytime within 24 months after randomization; or (3) the subject developed venous gangrene in the index leg within the first 24 months after randomization.	6-24 months
Secondary	Severity of presenting DVT Symptoms at 6 months	Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 6 months	6 months
Secondary	Severity of presenting DVT Symptoms at 12 months	Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 12 months	12 months
Secondary	Severity of presenting DVT Symptoms at 18 months	Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 18 months	18 months
Secondary	Severity of presenting DVT Symptoms at 24 months	Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 24 months	24 months
Secondary	Severity of presenting DVT Symptoms at 6 months	Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 6 months	6 months
Secondary	Severity of presenting DVT Symptoms at 12 months	Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 12 months	12 months
Secondary	Severity of presenting DVT Symptoms at 18 months	Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 18 months	18 months
Secondary	Severity of presenting DVT Symptoms at 24 months	Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 24 months	24 months
Secondary	Degree of Resolution of Thrombus with PCDT at 6 months.	Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.	6 months
Secondary	Degree of Resolution of Thrombus with PCDT at 12 months.	Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.	12 months
Secondary	Degree of Resolution of Thrombus with PCDT at 18 months.	Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.	18 months
Secondary	Degree of Resolution of Thrombus with PCDT at 24 months.	Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated.	24 months

External Links

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