Study to Learn More About the Benefits and Side-effects of Drugs Rivaroxaban and Apixaban Compared to the Drug Warfarin for Stroke Prevention in Patients With Rapid and Irregular Heartbeat Which is Not Due to a Heart-valve Fault (Non-valvular Atrial Fibrillation) in the UK Routine Clinical Practice (SiERRA UK)

Safety and Effectiveness of Rivaroxaban and Apixaban Compared to Warfarin in Non-valvular Atrial Fibrillation Patients in the Routine Clinical Practice in the UK

This population-based study will identify patients with rapid and irregular heartbeat which is not due to a fault with the heart valves (non-valvular atrial fibrillation) who initiate rivaroxaban, apixaban or warfarin as treatment for Stroke Prevention in Atrial Fibrillation (SPAF). Purpose of the study is to learn more about the safety and how well the drugs rivaroxaban, apixaban and warfarin work in patients appropriately and inappropriately receiving standard and reduced doses of each drug for reducing the risk of stroke in atrial fibrillation. Real world data from routine general practice stored in the primary care database in the UK, The Health Improvement Network (THIN), will be used for investigation.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Apixaban (Eliquis); Drug: Warfarin

Detailed Description

Primary objectives are to assess the safety and effectiveness of rivaroxaban, apixaban and warfarin based on the risk of intracranial hemorrhage and hemorrhagic strokes (safety) and ischemic stroke, systemic embolism and myocardial infarction (effectiveness). Secondary objectives comprise the assessment of the mentioned risks in subpopulations of patients with renal impairment or diabetes, mortality rates, and drug utilisation as well as patient characteristics before and after the first intracranial hemorrhage or ischemic stroke.

• Study Type: Observational
• Enrollment (Actual): 45164

Contacts and Locations

Study Locations

• United Kingdom
  • Many Sites, United Kingdom
    • Many facilities

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

UK population sample representative for age, sex and geographic distribution

Description

Inclusion Criteria:

• Patients with non-valvular atrial fibrillation
• New users of rivaroxaban, apixaban or warfarin
• At least one year enrollment with the general practice (GP)
• One year since first health contact recorded in THIN prior to the first prescription of a study drug

Exclusion Criteria:

• Patients with other recent indications of oral anticoagulant initiation
• Individuals on more than one oral anticoagulant on the start date
• Users of rivaroxaban apart from 15 / 20 mg daily dose
• Users of apixaban apart from 5 / 10 mg daily dose

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NVAF-patients_1; Adult patients with non-valvular atrial fibrillation (NVAF) and one year health records in the British THIN-database, who have not yet used rivaroxaban, apixaban and warfarin.	Drug: Rivaroxaban (Xarelto, BAY59-7939); Rivaroxaban at a dose of 15 or 20 mg once daily; Other Names: Non-Vitamin K Oral Anticoagulant (NOAC)
NVAF-patients_2; Adult patients with non-valvular atrial fibrillation (NVAF) and one year health records in the British THIN-database, who have not yet used rivaroxaban, apixaban and warfarin.	Drug: Apixaban (Eliquis); Apixaban at a dose of 2.5 or 5 mg twice daily; Other Names: Non-Vitamin K Oral Anticoagulant (NOAC)
NVAF-patients_3; Adult patients with non-valvular atrial fibrillation (NVAF) and one year health records in the British THIN-database, who have not yet used rivaroxaban, apixaban and warfarin.	Drug: Warfarin; Warfarin dose as prescribed by medical practitioner; Other Names: Vitamin K Antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of intracranial hemorrhage	Intracranial hemorrhage includes intracerebral hemorrhage, subarachnoid hemorrhage, subdural and epidural hemorrhage.	Retrospective analysis of data from 2012 to 2017
Risk of ischemic events	Ischemic events include ischaemic stroke / systemic embolism and myocardial infarction.	Retrospective analysis of data from 2012 to 2017

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of intracranial hemorrhage in NVAF-patients with renal impairment	Intracranial hemorrhage includes intracerebral hemorrhage, subarachnoid hemorrhage, subdural and epidural hemorrhage.	Retrospective analysis of data from 2012 to 2017
Risk of ischemic events in NVAF-patients with renal impairment	Ischemic events include ischaemic stroke / systemic embolism and myocardial infarction.	Retrospective analysis of data from 2012 to 2017
Risk of intracranial hemorrhage in NVAF-patients with diabetes	Intracranial hemorrhage includes intracerebral hemorrhage, subarachnoid hemorrhage, subdural and epidural hemorrhage.	Retrospective analysis of data from 2012 to 2017
Risk of ischemic events in NVAF-patients with diabetes	Ischemic events include ischaemic stroke / systemic embolism and myocardial infarction.	Retrospective analysis of data from 2012 to 2017
All-cause mortality	Rate of deaths from all causes.	Retrospective analysis of data from 2012 to 2017
Drug utilisation	Drug utilisation comprises a descriptive analysis of characteristics of index prescription, time trends and drug discontinuation.	Retrospective analysis of data from 2012 to 2017
Drug utilisation after first intracranial hemorrhage or ischemic stroke	Drug utilisation comprises a descriptive analysis of characteristics of index prescription, time trends and drug discontinuation.	Retrospective analysis of data from 2012 to 2017
Patient characteristics	Patient characteristics comprise a descriptive analysis of baseline characteristics, comorbidities, co-medications and time trends.	Retrospective analysis of data from 2012 to 2017
Patient characteristics after first intracranial hemorrhage or ischemic stroke	Patient characteristics comprise a descriptive analysis of baseline characteristics, comorbidities, co-medications and time trends.	Retrospective analysis of data from 2012 to 2017

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen, LP

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 28, 2019
• Primary Completion (ACTUAL): October 31, 2020
• Study Completion (ACTUAL): October 31, 2020

Study Registration Dates

• First Submitted: February 18, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (ACTUAL): February 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Under-dosing; Effectiveness; Oral anticoagulants; Stroke prevention in atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Protease Inhibitors; Micronutrients; Vitamins; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Rivaroxaban; Apixaban; Warfarin; Anticoagulants
• Other Study ID Numbers: 20343; EUPAS28234 (OTHER: ENCePP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

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