Tinzaparin Lead-In to Prevent the Post-Thrombotic Syndrome Phase IV Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 5
- 主要终点
- PTS at 6 months
研究概览
简要总结
The TILE pilot study will be a multicenter, open-label, assessor-blinded RCT (randomized control trial) comparing extended LMWH (Low Molecular Weight Heparin) vs. DOAC (Direct Oral Anticoagulants) to PTS (prevent post thrombotic syndrome) in patients with DVT (Deep Vein Thrombosis).
详细描述
The TILE pilot study will investigate the magnitude of difference in effectiveness between LMWH (low molecular weight heparin, tinzaparin) plus DOAC (Direct Oral Anticoagulants, rivaroxaban) vs. DOAC alone to determine the sample size and assess feasibility for a larger study assessing the effectiveness of an initial 3-week lead-in course of LMWH (tinzaparin) compared to DOAC alone (rivaroxaban) in patients with proximal DVT (Deep Vein Thrombosis) at high risk of developing PTS (Post-Thrombotic Syndrome). PTS is a frequent, costly and burdensome complication of DVT, especially for patients with iliac or femoral vein DVT who have a high risk of developing PTS and severe PTS. Anticoagulant therapy appears to influence this risk, with a higher frequency of PTS in patients with DVT who receive suboptimal treatment with a VKA (Vitamin K Antagonist). DOAC are expected to avoid this and other limitations of VKA therapy and have become the standard of care for patients with DVT. Extended treatment of DVT with LMWH, by providing more effective anticoagulation and by reducing inflammation, appears to restore venous patency and reduce venous reflux compared to VKA and probably to DOAC. Extended treatment of DVT with LMWH, therefore, has the potential to reduce PTS.
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
- Single (Outcomes Assessor)
盲法说明
Patients will be instructed not to disclose their treatment to PTS assessors
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with objectively confirmed acute (i.e. onset of symptoms <10 days) symptomatic iliac or common femoral DVT (DVT diagnosis will be made with a Compression Ultrasound (CUS) according to standardized consensus criteria)
排除标准
- •Age < 18 years
- •History of ipsilateral DVT (distal and/or proximal)
- •Active cancer
- •Thrombolysis or other invasive early thrombus removal technique to treat DVT or PE
- •Pregnant or breast feeding
- •Impaired renal function (creatinine clearance < 30 ml/min according to Cockcroft-Gault formula)
- •Concomitant use of drugs that interact with rivaroxaban (i.e. keto- or itraconazole, ritonavir)
- •Allergy or hypersensitivity to heparin or rivaroxaban, including heparin induced thrombocytopenia
- •Anticoagulant therapy contraindicated because of presence of active bleeding or condition with high risk of bleeding (e.g. peptic ulcer, acute or subacute septic endocarditis, uncontrolled severe hypertension, other)
- •Thrombocytopenia (platelet count < 100 x 109/L)
- •Liver disease (including Child-Pugh Class B and Class C) associated with coagulopathy
- •Body weight > 120 kg or < 40 kg
- •Need for treatment with daily NSAIDs or antiplatelet agent (ibuprofen < 1200 mg/day, aspirin ≤ 160 mg/day or clopidogrel ≤ 75 mg/day are permitted)
- •Treatment with therapeutic doses of anticoagulants for > 72 hours
- •Mechanical heart valve
- •Antiphospholipid syndrome
- •Sulphite sensitivity
- •Lactose sensitivity
- •Life expectancy < 1 year
- •Unable or unwilling to provide informed consent
研究组 & 干预措施
Tinzaparin
initial 3-week lead-in course of low molecular weight heparin (tinzaparin 175 units/Kg sc daily) followed by a direct oral anticoagulant (rivaroxaban 20mg po daily) for at least 3 months
干预措施: tinzaparin (Drug)
Rivaroxaban
Direct oral anticoagulant only (rivaroxaban 15mg po BID for 3 weeks followed by rivaroxaban 20mg po daily ) for at least 3 months
干预措施: Rivaroxaban (Drug)
结局指标
主要结局
PTS at 6 months
时间窗: 6 months post randomization
Proportion of patients with PTS at 6 months using the Villalta scale. PTS will be diagnosed using the Villalta scale. This clinical scale is the recommended standard to diagnose PTS.
Main feasibility
时间窗: 3 months post randomization
Main feasibility outcomes: a. Proportion of eligible patients, among patients screened b. Proportion of recruited patients, among patients who are eligible c. Proportion of patients who are compliant with tinzaparin, among recruited patients assigned to tinzaparin arm.
次要结局
- DVT-related leg pain(Two time points: at 10 days and at 3 months post randomization)
- Patient's satisfaction with treatment(Two time points: at 3 weeks and at 6 months post randomization)
- QOL (Quality of Life) score - SF-36(Three time points: at 3 weeks and at 6 months post randomization)
- QOL (Quality of Life) score - VEINES-QOL(Three time points: at 3 weeks and at 6 months post randomization)
- PTS severity(6 months post randomization)
- Villalta score at 10 days(10 days post randomization)
- Global Improvement(Two time points: at 10 days and at 3 months post randomization)
- SAEs(baseline to 6 months post randomization)
- Rate of lost to follow-up(6 months post randomization)