Pharmacokinetics of Apixaban in Peritoneal Dialysis

Pharmacokinetics and Safety Profile of Apixaban in Patients With Peritoneal Dialysis

Atrial fibrillation (AF) is fairly prevalent in patients with end stage renal disease (ESRD) with the prevalence estimated to be 3.8 - 27%. While it is reported that patient with peritoneal dialysis (PD) has a lower incidence of AF as compared to patient with haemodialysis (HD), the risk is still substantially higher than in the general population. AF is a known risk factor for embolic stroke and stroke causes significant morbidity and mortality. Anticoagulation in an effective treatment for the prevention of stroke in the general population. However, this is less clear in the ESRD populations.

Despite the risk of stroke is higher than general population, the management of AF in patients with ESRD remains controversial with limited and often conflicting result for the use of traditional vitamin K antagonists. It also showed an increased risk of bleeding with the use in ESRD patients.

With the advent of direct oral anticoagulants (DOACs), there is growing interest in advocating their uses and studies have been done to assess their safety profile. In fact, several randomized control trials are being performed. However, these studies are done in HD populations and there is no data for PD populations at all so far.

Given the physiology of drug clearance is different between the two renal replacement modalities, the investigators purpose to assess the pharmacokinetics and the safety profile of Apixaban in PD populations. By establishing the pharmacokinetics and its safety profile, apixaban may be a more attractive option for anticoagulation for AF or other venous thrombotic indications in PD population.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Apixaban

Detailed Description

Atrial fibrillation (AF) is fairly prevalent in patients with end stage renal disease (ESRD) with the prevalence estimated to be 3.8 - 27%. While it is reported that patient with peritoneal dialysis (PD) has a lower incidence of AF as compared to patient with haemodialysis (HD), the risk is still substantially higher than in the general population. AF is a known risk factor for embolic stroke and stroke causes significant morbidity and mortality. Anticoagulation in an effective treatment for the prevention of stroke in the general population. However, this is less clear in the ESRD populations.

Despite the risk of stroke is higher than general population, the management of AF in patients with ESRD remains controversial with limited and often conflicting result for the use of traditional vitamin K antagonists. It also showed an increased risk of bleeding with the use in ESRD patients.

With the advent of direct oral anticoagulants (DOACs), there is growing interest in advocating their uses and studies have been done to assess their safety profile. In fact, several randomized control trials are being performed. However, these studies are done in HD populations and there is no data for PD populations at all so far.

Given the physiology of drug clearance is different between the two renal replacement modalities, the investigators purpose to assess the pharmacokinetics and the safety profile of Apixaban in PD populations. By establishing the pharmacokinetics and its safety profile, apixaban may be a more attractive option for anticoagulation for AF or other venous thrombotic indications in PD population.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Winston WS Fung, MBBS; Phone Number: 852-55699689; Email: fws898@ha.org.hk
• Study Contact Backup: Name: Cheuk Chun C Szeto, MD; Phone Number: 852-35053146; Email: ccszeto@cuhk.edu.hk

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Recruiting
    • Department of Medicine & Therapeutics, Prince of Wales Hospital
    • Contact: Cheuk Chun Szeto, MD; Phone Number: 852-2632-3126; Email: ccszeto@cuhk.edu.hk
    • Contact: Winston WS Shing, MBBS; Phone Number: 852-55699689; Email: fws898@ha.org.hk
    • Principal Investigator: Cheuk Chun Szeto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

stable PD patients with non-valvular AF and with no significant residual renal function

Description

Inclusion Criteria:

• stable PD patients with non-valvular AF and with no significant residual renal function

Exclusion Criteria:

• increased risk of bleeding and those with contraindications to anticoagulation such as history of gastrointestinal bleeding, dual anti-platelet therapy, active malignancy, recent trauma and stroke

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; stable PD patients with non-valvular AF	Drug: Apixaban; Apixaban 2.5 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apixabn level	Blood anti-factor Xa activity	0 to 12 hours (14 time points)

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Prince of Wales Hospital, Shatin, Hong Kong
• Investigators: Principal Investigator: Winston WS Fung, MBBS, Prince of Wales Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: September 5, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 23, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: peritoneal dialysis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: CRE-2020.284

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No personal data will be shared.

Drug and device information, study documents

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