Pharmacokinetics of Rivaroxaban After Bariatric Surgery

Morbid Obesity Clinical Trial

— ABSORB  

Official title:

Pharmacokinetics and Pharmacodynamics of rivAroxaban After Bariatric Surgery and in mORBid Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04180436
• Other study ID #: ABSORB (29BRC19.0078)
• Status: Completed
• Phase: Phase 1
• Start date: January 15, 2020
• Est. completion date: June 27, 2022

Study information

• Verified date: July 2022
• Source: University Hospital, Brest
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: June 27, 2022
• Est. primary completion date: June 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Bariatric Surgery
• Morbid Obesity
• Obesity
• Obesity, Morbid

Intervention

Drug:
• rivaroxaban 20 mg once daily 8 days
Blood samples for the measurement of rivaroxaban PK parameters

Locations

Country	Name	City	State
France	CHRU de Brest	Brest

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Brest	Bayer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC of rivaroxaban	Rivaroxaban plasma concentrations was assessed by the reference method at the different sampling points to determine the area under the curve (AUC)	up to 8 days
Primary	Cmax of rivaroxaban	Cmax of rivaroxaban was assessed	up to 8 days
Primary	Tmax of rivaroxaban	Tmax of rivaroxaban was assessed	up to 8 days
Secondary	Prothrombin time	Prothrombin time of rivaroxaban was assessed	up to 8 days
Secondary	Activated partial thromboplatin time (aPTT)	Activated partial thromboplatin time was assessed	up to 8 days
Secondary	Fibrinogen levels	Fibrinogen levels was was assessed	up to 8 days
Secondary	Rivaroxaban anti-Xa activity	Rivaroxaban anti-Xa activity was assessed	up to 8 days
Secondary	Rate of bleedings	Treatment-Related Adverse Events were assessed	up to 15 days
Secondary	Other adverse events	Number of other adverse events than bleedings was assessed	up to 15 days
Secondary	Thrombin generation test of rivaroxaban	Thrombogram (thrombin generation test) data for each time analyzed allows measurement of peak height . These data will be used to model the PD of rivaroxaban and to estimate the PD variability.	up to 8 days
Secondary	Thrombin generation test of rivaroxaban	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.	up to 8 days