Clinical trial NCT04180436: Pharmacokinetics of Rivaroxaban After Bariatric Surgery
Official title: Pharmacokinetics and Pharmacodynamics of rivAroxaban After Bariatric Surgery and in mORBid Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bariatric Surgery
Morbid Obesity
Keywords: sleeve gastrectomy
gastric bypass
morbid obesity
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2019-11-27
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: AUC of rivaroxaban
timeFrame: up to 8 days
measure: Cmax of rivaroxaban
timeFrame: up to 8 days
measure: Tmax of rivaroxaban
timeFrame: up to 8 days
Secondary outcomes:
measure: Prothrombin time
timeFrame: up to 8 days
measure: Activated partial thromboplatin time (aPTT)
timeFrame: up to 8 days
measure: Fibrinogen levels
timeFrame: up to 8 days
measure: Rivaroxaban anti-Xa activity
timeFrame: up to 8 days
measure: Rate of bleedings
timeFrame: up to 15 days
measure: Other adverse events
timeFrame: up to 15 days
measure: Thrombin generation test of rivaroxaban
timeFrame: up to 8 days
measure: Thrombin generation test of rivaroxaban
timeFrame: up to 8 days
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU de Brest
Study officials:
References: