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

• ClinicalTrials.gov Identifier: NCT04684732
• Recruitment Status: Enrolling by invitation
• First Posted: December 24, 2020
• Last Update Posted: January 29, 2021
• Sponsor: Chulalongkorn University
• Collaborator: Thammasat University
• Information provided by (Responsible Party): Pheeraphat Sarppreuttikun, Chulalongkorn University

Study Description

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

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 241 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: Relationship Between Renal Function and Pharmacokinetics of Apixaban and Clinical Outcome of Apixaban in Thai Non-valvular Atrial Fibrillation Patients
• Actual Study Start Date: December 14, 2020
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: July 2021

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Number of participants with first event of stroke, transient ischemic attack, systemic embolism (SE), or all-cause death during the follow up period [ Time Frame: 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 ]
   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.
2. Number of patients with event of major or nonmajor (International Society on Thrombosis and Hemostasis [ISTH]) bleeding during the follow up period [ Time Frame: 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 ]

   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.

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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

Contacts and Locations

Locations

Thailand

King Chulalongkorn Memorial Hospital

Pathum Wan, Bangkok, Thailand, 10330

Sponsors and Collaborators

Chulalongkorn University

Thammasat University

More Information

• Responsible Party: Pheeraphat Sarppreuttikun, Principle Investigator, Chulalongkorn University
• ClinicalTrials.gov Identifier: NCT04684732
• Other Study ID Numbers: 632/63
• First Posted: December 24, 2020
• Last Update Posted: January 29, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pheeraphat Sarppreuttikun, Chulalongkorn University:

Apixaban; Pharmacokinetic; Pharmacodynamic; Cardioembolic stroke; Ischemic stroke

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes