Pharmacokinetics and Pharmacodynamics of rivAroxaban After Bariatric Surgery and in mORBid Obesity
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Cmax of rivaroxaban
研究概览
简要总结
Data on pharmacokinetics of rivaroxaban after bariatric surgery and in morbid obesity are sparse. The aim of this study is to assess the pharmacokinetic and pharmacodynamic parameters of rivaroxaban, used at a therapeutic anticoagulant dose, in patients with previous bariatric surgery, with sleeve gastrectomy or gastric bypass, and in morbid obese subjects.
Four groups of 16 subjects per group are studied: Morbid obese subjects / Subjects who have undergone gastric bypass surgery / Subjects who have undergone sleeve gastrectomy surgery / Non-operated control subjects matched for age and BMI with operated subjects.
All patients (obese, surgical patients, and controls) will receive rivaroxaban 20mg once daily during 8 days. Blood samples will be taken predose (Baseline) and 0.5, 1, 2, 3, 6, 9, 12 and 24h post rivaroxaban administration at day1 and day8. PK and PD parameters will be compared between groups in order to explore the impact of bariatric surgery, type of surgery and body mass index on the pharmacological profile of rivaroxaban.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Creatinine clearance measured by the Cockroft formula ≥ 60 mL / min
- •Patient meeting the specific criteria of one of the 4 groups:
- •morbidly obese patients with BMI ≥ 40
- •Patients operated by gastric bypass for over a year and with stable weight
- •Patients operated by sleeve gastrectomy for over a year and with stable weight
- •Control group: non-operated subjects but with an age and a BMI corresponding to those of the patients of the 2 operated groups.
排除标准
- •Indication for anticoagulant therapy, antiplatelet therapy or long-term nonsteroidal anti-inflammatory drugs
- •Clinically significant bleeding in progress
- •Taking oral or parenteral anticoagulants, or taking platelet antiaggregants within 4 weeks before inclusion
- •Congenital or acquired hemorrhagic disorders (eg von Willebrand disease, hemophilia)
- •Injury or disease, at significant risk of major bleeding (gastrointestinal ulceration, presence of malignant tumors with a high risk of bleeding, recent brain or spinal cord injury, recent cerebral, spinal or ophthalmic surgery, recent intracranial hemorrhage, known or suspected oesophageal varices , arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities)
- •Severe uncontrolled arterial hypertension
- •Active gastrointestinal disease potentially leading to bleeding disorders (esophagitis, gastritis, gastroesophageal reflux disease, chronic inflammatory bowel disease)
- •Vascular retinopathy
- •Bronchiectasis or history of pulmonary bleeding
- •Hypersensitivity to the active substance or to any of the excipients of rivaroxaban
- •Hepatic involvement associated with coagulopathy and clinically significant bleeding risk, including cirrhotic patients with Child Pugh Grade B or C score
- •Concomitant use of potent inhibitors or inducers of CYP3A4 and / or P-gp (azole antifungal or HIV protease inhibitor)
- •Participation in a paid and / or therapeutic study in the previous 3 months
- •Pregnant or lactating women,
- •Women of childbearing potential not using effective contraception
研究组 & 干预措施
morbidly obese patients with BMI ≥ 40
Morbidly obese patients with BMI ≥ 40
干预措施: rivaroxaban 20 mg once daily 8 days (Drug)
Patients operated by gastric bypass
Patients operated by gastric bypass for over a year and with stable weight
干预措施: rivaroxaban 20 mg once daily 8 days (Drug)
Patients operated by sleeve gastrectomy
Patients operated by sleeve gastrectomy for over a year and with stable weight
干预措施: rivaroxaban 20 mg once daily 8 days (Drug)
Control group: non-operated subjects
Control group: non-operated subjects but with an age and a BMI corresponding to those of the patients of the 2 operated groups.
干预措施: rivaroxaban 20 mg once daily 8 days (Drug)
结局指标
主要结局
Cmax of rivaroxaban
时间窗: up to 8 days
Cmax of rivaroxaban was assessed
AUC of rivaroxaban
时间窗: up to 8 days
Rivaroxaban plasma concentrations was assessed by the reference method at the different sampling points to determine the area under the curve (AUC)
Tmax of rivaroxaban
时间窗: up to 8 days
Tmax of rivaroxaban was assessed
次要结局
- Activated partial thromboplatin time (aPTT)(up to 8 days)
- Fibrinogen levels(up to 8 days)
- Other adverse events(up to 15 days)
- Prothrombin time(up to 8 days)
- Rivaroxaban anti-Xa activity(up to 8 days)
- Rate of bleedings(up to 15 days)
- Thrombin generation test of rivaroxaban(up to 8 days)