Pharmacokinetics of Rivaroxaban After Bariatric Surgery (ABSORB)

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

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.

Study Overview

• Status: Completed
• Conditions: Morbid Obesity; Bariatric Surgery
• Intervention / Treatment: Drug: rivaroxaban 20 mg once daily 8 days

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Brest, France, 29609
    • CHRU de Brest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: morbidly obese patients with BMI ≥ 40; Morbidly obese patients with BMI ≥ 40	Drug: rivaroxaban 20 mg once daily 8 days; Blood samples for the measurement of rivaroxaban PK parameters
Experimental: Patients operated by gastric bypass; Patients operated by gastric bypass for over a year and with stable weight	Drug: rivaroxaban 20 mg once daily 8 days; Blood samples for the measurement of rivaroxaban PK parameters
Experimental: Patients operated by sleeve gastrectomy; Patients operated by sleeve gastrectomy for over a year and with stable weight	Drug: rivaroxaban 20 mg once daily 8 days; Blood samples for the measurement of rivaroxaban PK parameters
Experimental: 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.	Drug: rivaroxaban 20 mg once daily 8 days; Blood samples for the measurement of rivaroxaban PK parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Cmax of rivaroxaban	Cmax of rivaroxaban was assessed	up to 8 days
Tmax of rivaroxaban	Tmax of rivaroxaban was assessed	up to 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prothrombin time	Prothrombin time of rivaroxaban was assessed	up to 8 days
Activated partial thromboplatin time (aPTT)	Activated partial thromboplatin time was assessed	up to 8 days
Fibrinogen levels	Fibrinogen levels was was assessed	up to 8 days
Rivaroxaban anti-Xa activity	Rivaroxaban anti-Xa activity was assessed	up to 8 days
Rate of bleedings	Treatment-Related Adverse Events were assessed	up to 15 days
Other adverse events	Number of other adverse events than bleedings was assessed	up to 15 days
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
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

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): June 21, 2022
• Study Completion (Actual): June 27, 2022

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: morbid obesity; sleeve gastrectomy; gastric bypass
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: ABSORB (29BRC19.0078)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No