Pharmacokinetics of Rivaroxaban After Bariatric Surgery
- Conditions
- Morbid ObesityBariatric Surgery
- Interventions
- Registration Number
- NCT04180436
- Lead Sponsor
- University Hospital, Brest
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Patients operated by gastric bypass rivaroxaban 20 mg once daily 8 days Patients operated by gastric bypass for over a year and with stable weight Patients operated by sleeve gastrectomy rivaroxaban 20 mg once daily 8 days Patients operated by sleeve gastrectomy for over a year and with stable weight morbidly obese patients with BMI ≥ 40 rivaroxaban 20 mg once daily 8 days Morbidly obese patients with BMI ≥ 40 Control group: non-operated subjects rivaroxaban 20 mg once daily 8 days Control group: non-operated subjects but with an age and a BMI corresponding to those of the patients of the 2 operated groups.
- Primary Outcome Measures
Name Time Method Cmax of rivaroxaban up to 8 days Cmax of rivaroxaban was assessed
AUC of rivaroxaban 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 up to 8 days Tmax of rivaroxaban was assessed
- Secondary Outcome Measures
Name Time Method Activated partial thromboplatin time (aPTT) up to 8 days Activated partial thromboplatin time was assessed
Fibrinogen levels up to 8 days Fibrinogen levels was was assessed
Other adverse events up to 15 days Number of other adverse events than bleedings was assessed
Prothrombin time up to 8 days Prothrombin time of rivaroxaban was assessed
Rivaroxaban anti-Xa activity up to 8 days Rivaroxaban anti-Xa activity was assessed
Rate of bleedings up to 15 days Treatment-Related Adverse Events were assessed
Thrombin generation test of rivaroxaban up to 8 days Thrombogram (thrombin generation test) data for each time analyzed allows measurement of thrombin generation potential (FTE). These data will be used to model the PD of rivaroxaban and to estimate the PD variability.
Trial Locations
- Locations (1)
CHRU de Brest
🇫🇷Brest, France