Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis--The ATTRACT Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 692
- 试验地点
- 56
- 主要终点
- Cumulative Incidence of Post-Thrombotic Syndrome (Villalta Scale)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic proximal DVT involving the iliac, common femoral, and/or femoral vein.
排除标准
- •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).
研究组 & 干预措施
A-Intervention
PCDT with intrathrombus delivery of recombinant tissue plasminogen activator (rt-PA, maximum allowable total dose 35 mg) into the DVT over a period of up to 24 hours. Three methods of initial rt-PA delivery will be used: 1) Trellis-8 Peripheral Infusion System - maximum first-session rt-PA dose 25 mg; 2) AngioJet Rheolytic Thrombectomy System - maximum first-session rt-PA dose 25 mg; or 3) Catheter-directed rt-PA infusion for up to 24 hours at 0.01 mg/kg/hr (maximum 1.0 mg/hr) via a multisidehole infusion catheter. Before and after PCDT, patients will receive standard DVT therapy as in the Control Arm
干预措施: Recombinant tissue plasminogen activator (rt-PA) (Drug)
结局指标
主要结局
Cumulative Incidence of Post-Thrombotic Syndrome (Villalta Scale)
时间窗: Between 6 and 24 months after randomization
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.
次要结局
- Major Non-post-thrombotic Syndrome Treatment Failure(Through 24 months)
- Any (Major + Minor) Bleeding(Within 24 months after randomization)
- Recurrent Venous Thromboembolism(Within 24 months after randomization)
- Moderate-to-severe Post-thrombotic Syndrome(Between 6 and 24 months after randomization)
- Death(Within 24 months after randomization)
- Change in General Quality of Life - Physical(Baseline to 24 months post-randomization)
- Any Treatment Failure(Through 24 months)
- Major Bleeding(Within 24 months after randomization)
- Any (Minor + Major) Bleeding(Within 10 days after randomization)
- Venous Clinical Severity Score(At 24 months)
- Severity of Post-thrombotic Syndrome (Villalta)(At 24 months)
- Change in General Quality of Life - Mental(Baseline to 24 months post-randomization)
- Change in Venous Disease-specific Quality of Life(Baseline to 24 months post-randomization)
- Change in Leg Pain Severity(Baseline to 30 days post-randomization)
- Change in Leg Circumference(Baseline to 30 days post-randomization)