Clinical trial NCT04684732: Relationship Between Renal Function and Pharmacokinetics of Apixaban and Clinical Outcome of Apixaban in Thai Non-valvular Atrial Fibrillation Patients
Official title: Relationship Between Renal Function and Pharmacokinetics of Apixaban and Clinical Outcome of Apixaban in Thai Non-valvular Atrial Fibrillation Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Atrial Fibrillation
Keywords: Apixaban
Pharmacokinetic
Pharmacodynamic
Cardioembolic stroke
Ischemic stroke
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: Thammasat University
First posted: 2020-12-24
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Steady state area under the concentration-time curve from pre-dose to 12 hours post-dose (AUC(0-12)) of Apixaban
timeFrame: pre-dose to 12 hours post-dose
Secondary outcomes:
measure: Number of participants with first event of stroke, transient ischemic attack, systemic embolism (SE), or all-cause death during the follow up period
timeFrame: 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
measure: Number of patients with event of major or nonmajor (International Society on Thrombosis and Hemostasis [ISTH]) bleeding during the follow up period
timeFrame: 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 outcomes:
measure: Steady-state maximum observed plasma concentration of Apixaban
timeFrame: pre-dose to 12 hours post-dose
measure: Steady-state minimum observed plasma concentration of Apixaban
timeFrame: pre-dose to 12 hours post-dose
measure: Steady state elimination of half-life of Apixaban
timeFrame: pre-dose to 12 hours post-dose
measure: Steady state Anti-Xa activity
timeFrame: pre-dose to 12 hours post-dose
Locations:
city: Pathum Wan
country: Thailand
facility: King Chulalongkorn Memorial Hospital
state: Bangkok
Study officials:
References: