Back to resultsPharmacokinetics of Rivaroxaban After Bariatric Surgery (ABSORB)
Primary Purpose
Bariatric Surgery, Morbid Obesity
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
rivaroxaban 20 mg once daily 8 days
Sponsored by
About this trial
This is an interventional treatment trial for Bariatric Surgery focused on measuring sleeve gastrectomy, gastric bypass, morbid obesity
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
Sites / Locations
- CHRU de Brest
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
morbidly obese patients with BMI ≥ 40
Patients operated by gastric bypass
Patients operated by sleeve gastrectomy
Control group: non-operated subjects
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
Cmax of rivaroxaban
Cmax of rivaroxaban was assessed
Tmax of rivaroxaban
Tmax of rivaroxaban was assessed
Secondary Outcome Measures
Prothrombin time
Prothrombin time of rivaroxaban was assessed
Activated partial thromboplatin time (aPTT)
Activated partial thromboplatin time was assessed
Fibrinogen levels
Fibrinogen levels was was assessed
Rivaroxaban anti-Xa activity
Rivaroxaban anti-Xa activity was assessed
Rate of bleedings
Treatment-Related Adverse Events were assessed
Other adverse events
Number of other adverse events than bleedings was assessed
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.
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.
Full Information
NCT ID
NCT04180436
First Posted
July 19, 2019
Last Updated
July 20, 2022
Sponsor
University Hospital, Brest
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT04180436
Brief Title
Pharmacokinetics of Rivaroxaban After Bariatric Surgery
Acronym
ABSORB
Official Title
Pharmacokinetics and Pharmacodynamics of rivAroxaban After Bariatric Surgery and in mORBid Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 15, 2020 (Actual)
Primary Completion Date
June 21, 2022 (Actual)
Study Completion Date
June 27, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Brest
Collaborators
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bariatric Surgery, Morbid Obesity
Keywords
sleeve gastrectomy, gastric bypass, morbid obesity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
morbidly obese patients with BMI ≥ 40
Arm Type
Experimental
Arm Description
Morbidly obese patients with BMI ≥ 40
Arm Title
Patients operated by gastric bypass
Arm Type
Experimental
Arm Description
Patients operated by gastric bypass for over a year and with stable weight
Arm Title
Patients operated by sleeve gastrectomy
Arm Type
Experimental
Arm Description
Patients operated by sleeve gastrectomy for over a year and with stable weight
Arm Title
Control group: non-operated subjects
Arm Type
Experimental
Arm Description
Control group: non-operated subjects but with an age and a BMI corresponding to those of the patients of the 2 operated groups.
Intervention Type
Drug
Intervention Name(s)
rivaroxaban 20 mg once daily 8 days
Intervention Description
Blood samples for the measurement of rivaroxaban PK parameters
Primary Outcome Measure Information:
Title
AUC of rivaroxaban
Description
Rivaroxaban plasma concentrations was assessed by the reference method at the different sampling points to determine the area under the curve (AUC)
Time Frame
up to 8 days
Title
Cmax of rivaroxaban
Description
Cmax of rivaroxaban was assessed
Time Frame
up to 8 days
Title
Tmax of rivaroxaban
Description
Tmax of rivaroxaban was assessed
Time Frame
up to 8 days
Secondary Outcome Measure Information:
Title
Prothrombin time
Description
Prothrombin time of rivaroxaban was assessed
Time Frame
up to 8 days
Title
Activated partial thromboplatin time (aPTT)
Description
Activated partial thromboplatin time was assessed
Time Frame
up to 8 days
Title
Fibrinogen levels
Description
Fibrinogen levels was was assessed
Time Frame
up to 8 days
Title
Rivaroxaban anti-Xa activity
Description
Rivaroxaban anti-Xa activity was assessed
Time Frame
up to 8 days
Title
Rate of bleedings
Description
Treatment-Related Adverse Events were assessed
Time Frame
up to 15 days
Title
Other adverse events
Description
Number of other adverse events than bleedings was assessed
Time Frame
up to 15 days
Title
Thrombin generation test of rivaroxaban
Description
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.
Time Frame
up to 8 days
Title
Thrombin generation test of rivaroxaban
Description
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.
Time Frame
up to 8 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
CHRU de Brest
City
Brest
ZIP/Postal Code
29609
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Pharmacokinetics of Rivaroxaban After Bariatric Surgery
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