Pharmacokinetics of Rivaroxaban After Bariatric Surgery

NCT04180436 | Completed Phase 1 DMC

• 1 other identifier: ABSORB (29BRC19.0078)
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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.

Conditions

Bariatric Surgery; Morbid Obesity

Keywords

sleeve gastrectomy; gastric bypass; morbid obesity

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Prothrombin time

  up to 8 days

• Activated partial thromboplatin time (aPTT)

  up to 8 days

• Fibrinogen levels

  up to 8 days

• Rivaroxaban anti-Xa activity

  up to 8 days

• Rate of bleedings

  up to 15 days

Study Arms (4)

morbidly obese patients with BMI ≥ 40

EXPERIMENTAL

Morbidly obese patients with BMI ≥ 40

Drug: rivaroxaban 20 mg once daily 8 days

Patients operated by gastric bypass

EXPERIMENTAL

Patients operated by gastric bypass for over a year and with stable weight

Drug: rivaroxaban 20 mg once daily 8 days

Patients operated by sleeve gastrectomy

EXPERIMENTAL

Patients operated by sleeve gastrectomy for over a year and with stable weight

Drug: rivaroxaban 20 mg once daily 8 days

Control group: non-operated subjects

EXPERIMENTAL

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

Interventions

rivaroxaban 20 mg once daily 8 days DRUG

Blood samples for the measurement of rivaroxaban PK parameters

Control group: non-operated subjects; Patients operated by gastric bypass; Patients operated by sleeve gastrectomy; morbidly obese patients with BMI ≥ 40

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Indication for anticoagulant therapy, antiplatelet therapy or long-term nonsteroidal anti-inflammatory drugs
• Clinically significant bleeding in progress
• 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

Sponsors & Collaborators

• University Hospital, Brest: lead
• Bayer: collaborator

Study Sites (1)

CHRU de Brest

Brest, France, 29609, France

Location

Related Publications (1)

• Leven C, Delavenne X, Roche C, Bressollette L, Couturaud F, Lacut K, Thereaux J. Full-dose rivaroxaban in patients with a history of bariatric surgery: bridging the knowledge gap through a phase 1 study. J Thromb Haemost. 2024 Oct;22(10):2844-2854. doi: 10.1016/j.jtha.2024.06.024. Epub 2024 Jul 11.

  PMID: 39002729 RESULT

MeSH Terms

Conditions

Obesity, Morbid

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2019
• First Posted: November 27, 2019
• Study Start: January 15, 2020
• Primary Completion: June 21, 2022
• Study Completion: June 27, 2022
• Last Updated: December 3, 2025

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available after the publication of result and ending fifteen years following the last visit of the last patient
• 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.

Locations

FR (1)