Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test in Patients At Extremely High Risk of Postoperative Venous Thromboembolism.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Symptomatic and asymptomatic venous thrombosis by postoperative day 10
研究概览
简要总结
The aim of this study is to evaluate the efficacy and safety of individual dose adjustment of low molecular weight heparin (LMWH) based on the results of the thrombodynamics test (TD) in patients at extremely high risk of postoperative venous thromboembolism (VTE).
This is a single-center, open-label, randomized clinical study with a blinded assessor for primary efficacy outcome.
Patients after elective or emergent major surgery having 10 or more Caprini scores at the baseline, who already received two subcutaneous injections of enoxaparin: 40 mg at 6-12 hours after the surgery ("key injection 1") and 40 mg at 12 hours after the previous injection ("key injection 2"), who had no VTE at the baseline, and who signed informed consent, are subjected to laboratory examination by the TD.
Blood samples are taken 12 hours after the "key injection 1" and 24 hours after the "key injection 2". If one of the relevant parameters of the TD (initial velocity of clot growth rate and clot size) exceeds the set threshold, the Caprini scores are recalculated adding 3 points for "other thrombophilic state" confirmed by the thrombodynamics. The patient may be included in the study if the new sum exceeds 13 points (initial 10 scores + additional 3 scores). Within 60 hours from the surgery, the included patients are randomly allocated to one of two groups: Experimental or Control. Patients in the Control group continue to receive the standard dose of enoxaparin 40 mg every 24 hours (once daily). In the Experimental group, the dose of enoxaparin is increased to 30 mg every 12 hours (twice daily).
Blood samples for TD are taken during the next two days at 24 hours after the administration of each daily dose of enoxaparin.
A whole leg duplex ultrasound scan (DUS) is performed in all patients during the screening period and at 7-10 days after the surgery or in case of any suspicion for deep vein thrombosis (DVT) or superficial vein thrombosis (SVT). Computed tomography pulmonary angiography (CTPA) is carried out in any clinical suspicion for pulmonary embolism (PE). An autopsy is performed in all dead patients.
The total follow-up period is 30 days. After discharge, patients are invited to the hospital for clinical examination with DUS or interviewed by phone to identify symptomatic VTE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
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
- •performed major surgery;
- •performed the key injection 1 and the key injection 2 of enoxaparin 40 mg;
- •performed thrombodynamics test at 12 hours after the key injection 1 and at 24 hours after the key injection 2;
- •at least one of the relevant TD parameters exceeds the set threshold: initial velocity of clot growth >62.5 μm / min at 12 hours after the key injection 1, or initial velocity of clot growth >64.5 μm / min at 24 hours after the key injection 2, or clot size >1333.5 μm at 12 hours after the key injection 1, or clot size >1351.5 μm at 24 hours after the key injection 2;
- •Caprini score of 13 and higher after recalculation with the results of the TD test;
- •infirmed consent is given.
排除标准
- •60 or more hours passed since the end of surgery;
- •venous thrombosis at the baseline;
- •performed partial occlusion of the inferior vena cava (plication, filter);
- •indications for the use of anticoagulants in different regimen;
- •high risk of bleeding;
- •contraindication to anticoagulation;
- •contraindication to elastic compression;
- •inability for blood sampling from a peripheral vein;
- •anticipated death within 5 days or less.
研究组 & 干预措施
Control
Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings
干预措施: Standard Enoxaparin 40 mg once-daily before randomization (Drug)
Control
Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings
干预措施: Standard Enoxaparin 40 mg once-daily after randomization (Drug)
Control
Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings
干预措施: Anti-embolic elastic compression stockings (Device)
Control
Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings
干预措施: Thrombodynamic test (TD) (Diagnostic Test)
Experimental
Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings
干预措施: Standard Enoxaparin 40 mg once-daily before randomization (Drug)
Experimental
Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings
干预措施: Escalated Enoxaparin 30 mg twice-daily after randomization (Drug)
Experimental
Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings
干预措施: Anti-embolic elastic compression stockings (Device)
Experimental
Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings
干预措施: Thrombodynamic test (TD) (Diagnostic Test)
结局指标
主要结局
Symptomatic and asymptomatic venous thrombosis by postoperative day 10
时间窗: day 10 after surgery
The number of patients with a combination of asymptomatic DVT or SVT revealed by routine DUS performed by blinded assessor between 7 and 10 postoperative day and symptomatic DVT or SVT confirmed by unscheduled DUS.
次要结局
- The number of patients with the reduction of any relevant parameter of the TD test by postoperative day 5(day 5 after surgery)
- The number of patients with the normalization of every parameter of the TD test by postoperative day 5(day 5 after surgery)
- Death by postoperative day 10(day 10 after surgery)
- Death by postoperative day 30(day 30 after surgery)
- The number of patients with the reduction of all relevant parameters of the TD test by postoperative day 5(day 5 after surgery)
- Symptomatic and asymptomatic venous thromboembolism by postoperative day 30(day 30 after surgery)
- Clinically relevant non-major bleeding by postoperative day 30(day 30 after surgery)
- Symptomatic and asymptomatic venous thromboembolism by postoperative day 10(day 10 after surgery)
- Symptomatic pulmonary embolism by postoperative day 10(day 10 after surgery)
- Major bleeding by postoperative day 30(day 30 after surgery)
- Minor bleeding by postoperative day 30(day 30 after surgery)
- Fatal pulmonary embolism by postoperative day 10(day 10 after surgery)
研究者
Kirill Lobastov
Associate Professor
Pirogov Russian National Research Medical University