Relationship Between Renal Function and Pharmacokinetics of Apixaban and Clinical Outcome of Apixaban in Thai Non-valvular Atrial Fibrillation Patients

The purpose of this study is to assess pharmacokinetics and pharmacodynamics of Apixaban and clinical outcome of Apixaban in Thai patients with nonvalvular atrial fibrillation with varying degree of creatinine clearance

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation

Detailed Description

This study is divided into two parts.

The first part is a multiple dose pharmacokinetic and pharmacodynamics study of Apixaban in patient with stable renal function. The primary purpose of this study is to provide a clear understanding of the effect of creatinine clearance on pharmacokinetics and pharmacodynamics of Apixaban among Thai patients with nonvalvular atrial fibrillation. To assess the pharmacokinetics and pharmacodynamics of Apixaban, This study will enroll 30 subjects who meet the inclusion criteria.

The second part of this study will retrospectively determine the occurrent of clinical outcome between patients who were prescribed apixaban dose concordant and discordant to the drug leaflet. A total of 241 subjects will be recruited. The follow up period will begin from the time of initiation of apixaban until occurrent of stoke, transient ischemic attack, systemic embolism, bleeding, or death.

• Study Type: Observational
• Enrollment (Anticipated): 241

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Pathum Wan, Bangkok, Thailand, 10330
      • King Chulalongkorn Memorial Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Thai patients with nonvalvular atrial fibrillation receiving a stable dose of apixaban for primary or secondary prevention of stroke, transient ischemic attack, or systemic embolism.

Description

Part I

Inclusion Criteria:

• Patients with nonvalvular atrial fibrillation
• Patients who is receiving a stable dose of apixaban for primary or secondary prevention of stroke, transient ischemic attack, and systemic embolism.

Exclusion Criteria:

• Pregnant or lactating
• End stage renal disease patients who required chronic renal replacement therapy to sustained life
• History of acute kidney injury within the previous 3 months
• Severe hepatic impairment (Child-Pugh class C)
• Any gastrointestinal disorder that could impact the absorption of study drug
• CYP3A4 Moderate/Strong Inhibitors: ketoconazole, itraconazole, voriconazole, posaconazole, ritonavir, naproxen, clarithromycin, rifampicin, phenytoin, carbamazepine, phenobarbital, diltiazem, and St.John's Wort

Part II

Inclusion Criteria:

• Patients with nonvalvular atrial fibrillation
• Patients who was prescribed apixaban for primary or secondary prevention of stroke, transient ischemic attack, and systemic embolism.

Exclusion Criteria:

• Pregnant or lactating

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Apixaban dose concordant to leaflet; Patients who were prescribed apixaban dose concordant to apixaban leaflet approved by Thai FDA
Apixaban dose discordant to leaflet; Patients who were prescribed apixaban dose discordant to apixaban leaflet approved by Thai FDA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady state area under the concentration-time curve from pre-dose to 12 hours post-dose (AUC(0-12)) of Apixaban	AUC(0-12) is measured by plasma concentration of apixaban over time. The mean are reported in nanogram hours per milliliter (ng*h/mL).	pre-dose to 12 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with first event of stroke, transient ischemic attack, systemic embolism (SE), or all-cause death during the follow up period	Diagnosis of stroke is defined as the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE is defined as a clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed until July 31, 2020
Number of patients with event of major or nonmajor (International Society on Thrombosis and Hemostasis [ISTH]) bleeding during the follow up period	ISTH major bleeding criteria is defined as a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more, and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal. ISTH nonmajor bleeding is defined as clinically overt, that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event, that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed until July 31, 2020

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady-state maximum observed plasma concentration of Apixaban	Maximum observed drug concentration in plasma after administration (Cmax) of apixaban at steady-state	pre-dose to 12 hours post-dose
Steady-state minimum observed plasma concentration of Apixaban	Minimum observed drug concentration in plasma after administration (Cmin) of apixaban at steady-state	pre-dose to 12 hours post-dose
Steady state elimination of half-life of Apixaban	Mean terminal phase plasma t½ of apixaban at steady-state	pre-dose to 12 hours post-dose
Steady state Anti-Xa activity	Anti-Xa activity will be measured by chromogenic anti-Xa activity assay	pre-dose to 12 hours post-dose

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Collaborators: Thammasat University

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetic; Pharmacodynamic; Apixaban; Ischemic stroke; Cardioembolic stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 632/63

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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