A Prospective, Randomised Controlled Trial Comparing Weight-based Tinzaparin Versus Weight-based Enoxaparin for Peri-operative Thromboprophylaxis in Patients Undergoing Bariatric Surgery: Evaluation of Anti-Xa Levels and Clinical Outcomes.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Proportion of participants achieving prophylactic anti-Xa levels
研究概览
简要总结
Blood clots in the legs or lungs (called venous thromboembolism or VTE) are one of the most serious complications after weight loss surgery. Most blood clots occur after patients go home from hospital, within the first 30 days after surgery. To prevent blood clots, all patients having weight loss surgery receive a daily blood-thinning injection for 21 days after their operation.
Two blood-thinning injections are currently used at St Vincent's University Hospital for this purpose: enoxaparin (Clexane®) and tinzaparin (Innohep®). Both belong to a group of medicines called low molecular weight heparins (LMWHs). Patients with obesity process these medicines differently to the general population, and previous studies from our hospital have shown that fewer than 53% of patients achieve adequate blood-thinning levels with either injection when measured by a blood test called an anti-Xa level.
Patients will be randomly assigned (like a coin toss) to receive either tinzaparin or enoxaparin for 21 days after their surgery. Both injections are already in routine use at this hospital. A single extra blood sample will be taken on the second day after surgery to measure the anti-Xa level, which tells us whether the injection is providing adequate protection against blood clots. This blood sample will be taken at the same time as routine post-operative blood tests so that no additional blood draws are required.
The study will also look at rates of blood clots and bleeding events within 30 days of surgery, and will ask patients to complete a short questionnaire at their six-week follow-up appointment about their experience with the injection.
详细描述
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality following bariatric surgery, with a reported incidence of symptomatic DVT of 0.4-3% and PE of 0.3-2%. Over 80% of VTE events occur after hospital discharge, within 30 days of surgery. Obesity is an independent risk factor for VTE through venous stasis, a chronic pro-inflammatory and hypercoagulable state, adipokine dysregulation, and endothelial dysfunction. The pneumoperitoneum and reverse Trendelenburg positioning required for laparoscopic bariatric surgery further amplify venous stasis and thrombotic risk intraoperatively.
Low molecular weight heparin (LMWH) is the cornerstone of pharmacological VTE prophylaxis in bariatric surgery. LMWH exerts its anticoagulant effect via antithrombin-mediated Factor Xa inhibition, and pharmacodynamic adequacy can be assessed by measurement of anti-Xa activity. The American Society for Metabolic and Bariatric Surgery (ASMBS) 2021 position statement recommends a target prophylactic anti-Xa range of 0.2-0.4 IU/mL, measured at 4 hours after the third consecutive dose. The pharmacokinetics of LMWH are significantly altered in patients with severe obesity due to increased volume of distribution, altered renal clearance, elevated Factor Xa activity, and aberrant subcutaneous absorption, reducing the predictability of standard dosing regimens in this population.
Our research group at St Vincent's University Hospital (SVUH) has completed two prospective observational pilot studies. The first (Ethics Ref: RS22-017; n=20) examined weight-stratified enoxaparin dosing and found that 52.2% of patients achieved prophylactic anti-Xa levels. The second (Ethics Ref: RS25-035; n=51) examined weight-based tinzaparin (50 anti-Xa IU/kg once daily) and found that 47.1% achieved prophylactic anti-Xa levels - the first study of tinzaparin pharmacokinetics in a bariatric surgery population. A systematic review and meta-analysis conducted by the research team estimated a pooled prophylactic anti-Xa rate of 0.68 for weight-stratified enoxaparin dosing in the published literature. These data directly informed the design and power calculation of this RCT.
To our knowledge, no adequately powered randomised controlled trial has directly compared anti-Xa activity between tinzaparin and enoxaparin in a bariatric surgery population. The OAT-RCT is designed to address this gap using prospective anti-Xa level monitoring as its primary endpoint.
Design: Single-centre, prospective, parallel-group, open-label, randomised controlled superiority trial at SVUH, Dublin, Ireland.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is an open-label trial. The laboratory scientist performing anti-Xa analysis and the study statistician performing the primary outcome analysis are blinded to treatment allocation. The statistician will remain blinded until the primary analysis is complete.
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
- •Age ≥18 years
- •BMI ≥40 kg/m², or BMI ≥35 kg/m² with at least one obesity-related comorbidity (type 2 diabetes, hypertension, obstructive sleep apnoea, dyslipidaemia, or metabolic dysfunction-associated steatotic liver disease (MASLD))
- •Scheduled to undergo laparoscopic bariatric surgery (sleeve gastrectomy or gastric bypass) at St Vincent's University Hospital, Dublin, Ireland
- •Capacity to provide written informed consent
排除标准
- •Current therapeutic anticoagulation for any indication Known allergy or hypersensitivity to tinzaparin, enoxaparin, heparin, or any heparin-derived product, including documented heparin-induced thrombocytopaenia (HIT) Any other contraindication to LMWH therapy Severe renal impairment (eGFR <30 mL/min/1.73m²) Known haematological disorder or coagulopathy Pregnancy, breastfeeding, or planning pregnancy during the study period Active major bleeding or high bleeding risk at the discretion of the treating clinician Inability to provide written informed consent Participation in another interventional clinical study within 30 days prior to enrolment
研究组 & 干预措施
Weight-based Tinzaparin
Tinzaparin (Innohep®, LEO Pharma) administered subcutaneously once daily at a dose of 50 anti-Xa IU/kg total body weight, commencing on post-operative day 1 and continuing for 21 days. Administered via subcutaneous injection into the abdominal wall. Anti-Xa level measured at 4 hours (±30 minutes) after the third consecutive dose on post-operative day 2.
干预措施: Anti-Xa Activity Monitoring (Diagnostic Test)
Weight-stratified Enoxaparin
Enoxaparin (Clexane®, Sanofi) administered subcutaneously twice daily, commencing on post-operative day 1 and continuing for 21 days. Dose: 40 mg twice daily for patients weighing ≤150 kg; 60 mg twice daily for patients weighing >150 kg. Administered via subcutaneous injection into the abdominal wall. Anti-Xa level measured at 4 hours (±30 minutes) after the third consecutive dose on post-operative day 2.
干预措施: Anti-Xa Activity Monitoring (Diagnostic Test)
Weight-based Tinzaparin
Tinzaparin (Innohep®, LEO Pharma) administered subcutaneously once daily at a dose of 50 anti-Xa IU/kg total body weight, commencing on post-operative day 1 and continuing for 21 days. Administered via subcutaneous injection into the abdominal wall. Anti-Xa level measured at 4 hours (±30 minutes) after the third consecutive dose on post-operative day 2.
干预措施: Tinzaparin (Leo) (Drug)
Weight-stratified Enoxaparin
Enoxaparin (Clexane®, Sanofi) administered subcutaneously twice daily, commencing on post-operative day 1 and continuing for 21 days. Dose: 40 mg twice daily for patients weighing ≤150 kg; 60 mg twice daily for patients weighing >150 kg. Administered via subcutaneous injection into the abdominal wall. Anti-Xa level measured at 4 hours (±30 minutes) after the third consecutive dose on post-operative day 2.
干预措施: enoxaparin (Drug)
结局指标
主要结局
Proportion of participants achieving prophylactic anti-Xa levels
时间窗: Post-operative day 2 (4 hours after third LMWH dose)
Proportion of participants achieving a prophylactic anti-Xa level of 0.2-0.4 IU/mL, measured at 4 hours (±30 minutes) after the third consecutive LMWH dose on post-operative day 2, as specified by the ASMBS 2021 position statement. Measured using a CE-marked chromogenic anti-Xa assay at the SVUH Haematology Laboratory.
次要结局
- Incidence of clinically significant bleeding events(30 days post-operatively)
- Incidence of venous thromboembolism(30 days post-operatively)
- Proportion achieving sub-prophylactic anti-Xa levels(Post-operative day 2 (4 hours after third LMWH dose))
- Proportion achieving supra-prophylactic anti-Xa levels(Post-operative day 2 (4 hours after third LMWH dose))
- Correlation between anti-Xa level and body habitus(Post-operative day 2)
- Adverse drug reactions(30 days post-operatively)
- Patient-reported treatment adherence and injection site tolerability(6 weeks post-operatively)
- Patient-reported treatment satisfaction(6 weeks post-operatively)