PK of Rivaroxaban in Bariatric Patients - Extension

Pharmacokinetics and Pharmacodynamics of Single Doses of Rivaroxaban in Obesity Patients Before and After Bariatric Surgery - The Extension Study

Aim of this clinical Trial is the assessment of rivaroxaban PK/PD parameters in patients 6-8 months after bariatric surgery

Study Overview

• Status: Completed
• Conditions: Prophylaxis of Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban 10 mg

Detailed Description

Weight loss after bariatric surgery can putatively alter drug disposition of rivaroxaban. This may be due to an altered intestinal adaptations several months after the surgical procedure. The aim of this clinical trial is to investigate pharmacokinetic and pharmacodynamic parameters after single application of 10 mg rivaroxaban in patients with prior bariatric intervention (Roux-en-y-gastric bypass or sleeve gastrectomy 6-8 months ago). PK/PD parameters will be assessed during 12 hours after application of rivaroxaban.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • University Hospital, Inselspital Berne

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient with past elective bariatric surgery (Roux-en-Y gastric bypass surgery or sleeve gastrectomy 6-8 months ago)
• Patient aged 18 years and older
• BMI ≥ 35 kg/m2
• Women of child-bearing age: Willingness of using a double barrier contraception method during the study
• Written, informed consent

Exclusion Criteria:

• Intake of oral anticoagulants (phenprocoumon, acenocoumarol, dabigatran, etexilate, apixaban etc.) 4 weeks prior to inclusion in the study
• Application of parenteral anticoagulants (unfractionated heparin, low molecular weight heparins, heparin derivates (fondaparinux etc.) 4 weeks prior to inclusion in the study
• Pharmacologic platelet inhibition 4 weeks prior to inclusion in the study
• Known coagulation disorders (e.g. Willebrand's disease, haemophilia)
• Evidence for deep vein thrombosis or pulmonary embolism in the personal history or in the history of first degree relatives
• Medical condition that is associated with an increased risk for VTE, i.e. active cancer disease, lupus erythematodes chronic inflammatory bowel disease
• Active, clinically significant bleeding
• Congenital or acquired bleeding disorder
• Uncontrolled severe hypertension
• Active gastrointestinal disease that can potentially lead to bleeding disorder: oesophagitis, gastritis, gastroesophageal reflux disease, chronic inflammatory bowel disease
• Vascular retinopathy
• Bronchiectasis or history of pulmonary bleeding
• Prior stroke or TIA
• Hereditary galactose intolerance, Lapp lactase deficiency, glucose-lactose malabsorption
• Severe renal impairment with a creatinine clearance (GFR) of < 30ml/min
• Positive pregnancy test, pregnancy or nursing women
• High risk of bleeding (e.g. active ulcerative gastrointestinal disease)
• Known intolerance of the study medication rivaroxaban
• Concomitant treatment with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, lopinavir, ritonavir, indinavir)
• Concomitant treatment with an P-glycoprotein inhibitor and weak or moderate CYP3A4 inhibitor (e.g. erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Rivaroxaban Arm	Drug: Rivaroxaban 10 mg; At study month 7 (+/-1 month), patients receive at 8 a.m. a single dose of 10 mg rivaroxaban. Study specific blood tubes are sampled the same day at the indicated time points from T -1h to T 12h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC of rivaroxaban	1 year
Cmax of rivaroxaban	1 year
Tmax of rivaroxaban	1 year
Prothrombin time (PT)	1 year
Activated partial thromboplastin time (aPTT)	1 year
Levels of Prothrombin fragment (F1+F2)	1 year
Levels of Thrombin-antithrombin-complexes (TAT)	1 year
Levels of D-Dimers	1 year

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: University of Lausanne Hospitals
• Investigators: Study Chair: Dino Kröll, MD, University Hospital Inselspital, Berne

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: June 17, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (Estimate): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 025/15_2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO