Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis

Washington University School of Medicine692 enrolled

Overview

The purpose of this study is to determine if the use of adjunctive Pharmacomechanical Catheter Directed Thrombolysis, which includes the intrathrombus administration of rt-PA--Activase (Alteplase),can prevent the post-thrombotic syndrome(PTS)in patients with symptomatic proximal deep vein thrombosis(DVT)as compared with optimal standard DVT therapy alone.

Activase, the study drug, is a fibrinolytic drug that is indicated for use in acute myocardial infarction, acute ischemic stroke, and acute massive pulmonary embolism in adults. Previous studies have established the ability of rt-PA to lyse venous thrombus in patients with deep vein thrombosis (DVT), and suggest that successful rt-PA mediated thrombolysis can prevent the post-thrombotic syndrome (PTS), a morbid, late complication of DVT that occurs in nearly 50% of patients. rt-PA is delivered directly into venous thrombus using a catheter/device which is embedded within the thrombus by a physician under imaging guidance. This method of rt-PA delivery, pharmacomechanical catheter-directed intrathrombus thrombolysis (PCDT),is thought to be safer, more effective, and more efficient than previous methods. The question of whether PCDT using rt-PA improves long-term DVT patient outcomes with acceptable risk and cost has not yet been addressed. The rationale for performing the ATTRACT Trial is based upon: * the major burden of PTS on DVT patients and the U.S. healthcare system * the association between rapid clot lysis and prevention of PTS * the proven ability of rt-PA to dissolve venous thrombus in proximal DVT * recent advances in CDT methods which may lower bleeding risk * the major clinical controversy on whether CDT should be routinely used for first-line DVT therapy

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

692

Eligibility

Sex: ALLMin age: 16 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Symptomatic proximal DVT involving the iliac, common femoral, and/or femoral vein. Exclusion Criteria: * Age less than 16 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 iliac and/or common femoral vein; or b) for which thrombolysis is planned as part of the initial therapy. * Limb-threatening circulatory compromise. * Pulmonary embolism 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 glomerular filtration rate \[GFR\] \< 60 ml/min) or severe renal impairment in non-diabetic patients (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, cardiopulmonary resuscitation, 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 \> 180 mmHg or diastolic \> 105 mmHg). * Pregnant (positive pregnancy test, women of childbearing potential must be tested). * Recently (\< 1 mo) had thrombolysis or is participating in another investigational drug study. * Use of a thienopyridine antiplatelet drug (except clopidogrel) in the last 5 days. * Life expectancy \< 2 years or chronic non-ambulatory status. * Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).

Outcomes

Primary Outcomes

Cumulative Incidence of Post-Thrombotic Syndrome (Villalta Scale)

Patients who experienced one of the following occurrences in the index leg between the 6 month and 24 month post-randomization follow-up visits, inclusive: 1) Villalta score of 5 or greater; 2) leg ulcer; or 3) late endovascular procedure performed to treat severe venous disease. The Villalta scale ranges from 0-33 points, with higher scores being worse.

Time frame: Between 6 and 24 months after randomization

Secondary Outcomes

Major Non-post-thrombotic Syndrome Treatment Failure

A major non-post-thrombotic-syndrome treatment failure refers to when any of three events occurred in the index leg: 1) an unplanned endovascular procedure to treat severe venous symptoms within 6 months post-randomization; 2) venous gangrene within 6 months; or 3) an amputation within 24 months.

Time frame: Through 24 months

Any Treatment Failure

Composite of PTS and major non-PTS treatment failure

Time frame: Through 24 months

Moderate-to-severe Post-thrombotic Syndrome

Proportion of patients with Villalta score of 10 or higher at any time between the 6 month and 24 month follow-up visits, inclusive. The Villalta scale ranges from 0-33 points, with higher scores being worse.

Time frame: Between 6 and 24 months after randomization

Major Bleeding

Defined as clinically overt bleeding that is associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g. intracranial, intraspinal).

Time frame: Within 10 days after randomization

Major Bleeding

Defined as clinically overt bleeding that was associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g. intracranial, intraspinal).

Time frame: Within 24 months after randomization

Any (Minor + Major) Bleeding

Clinically overt bleeding that occurred through 10 days post-randomization

Time frame: Within 10 days after randomization

Any (Major + Minor) Bleeding

Clinically overt bleeding that occurred within 24 months post-randomization

Time frame: Within 24 months after randomization

Recurrent Venous Thromboembolism

Proportion of patients with symptomatic recurrent venous thromboembolism (including DVT and/or PE)

Time frame: Within 10 days after randomization

Recurrent Venous Thromboembolism

Symptomatic recurrent venous thromboembolism (DVT and/or PE)

Time frame: Within 24 months after randomization

Death

All-cause mortality

Time frame: Within 10 days after randomization

Death

All-cause mortality

Time frame: Within 24 months after randomization

Severity of Post-thrombotic Syndrome (Villalta)

Mean Villalta scale score at the specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

Time frame: At 6 months

Severity of Post-thrombotic Syndrome (Villalta)

Mean Villalta scale score at the specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

Time frame: At 12 months

Severity of Post-thrombotic Syndrome (Villalta)

Mean Villalta scale score at specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

Time frame: At 18 months

Severity of Post-thrombotic Syndrome (Villalta)

Mean Villalta scale score at specified follow-up visit. Villalta score ranges from 0-33 points, with higher scores being worse.

Time frame: At 24 months

Venous Clinical Severity Score

Mean Venous Clinical Severity Score (VCSS) at the specified follow-up visit; range 0-27 (did not use compression item), higher score is worse

Time frame: At 6 months

Venous Clinical Severity Score

Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)

Time frame: At 12 months

Venous Clinical Severity Score

Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)

Time frame: At 18 months

Venous Clinical Severity Score

Mean VCSS score at the specified follow-up visit; range 0-27 (did not use compression item)

Time frame: At 24 months

Change in General Quality of Life - Physical

Short-Form-36 Health Survey, Version 2, Physical Component Summary (PCS) Scale. Range of scores 0-100 with higher scores representing better quality of life.

Time frame: Baseline to 24 months post-randomization

Change in General Quality of Life - Mental

Short-Form-36 Health Survey, Version 2, Mental Component Summary (MCS) Scale. Range of scores 0-100 with higher scores representing better quality of life.

Time frame: Baseline to 24 months post-randomization

Change in Venous Disease-specific Quality of Life

Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) questionnaire. Range of scores 0-100 with higher scores representing better quality of life, and higher change scores representing greater improvement from baseline.

Time frame: Baseline to 24 months post-randomization

Change in Leg Pain Severity

Likert pain scale ranging from 1-7, with higher scores representing a greater intensity of pain

Time frame: Baseline to 10 days post-randomization

Change in Leg Pain Severity

Likert pain scale ranging from 1-7, with higher scores representing a greater intensity of pain

Time frame: Baseline to 30 days post-randomization

Change in Leg Circumference

Mean calf circumference measured 10 cm below the tibial tuberosity

Time frame: Baseline to 10 days post-randomization

Change in Leg Circumference

Mean calf circumference measured 10 cm below the tibial tuberosity

Time frame: Baseline to 30 days post-randomization

Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis

Overview

Conditions

Interventions

Eligibility

Locations (56)

Outcomes

Primary Outcomes

Secondary Outcomes