A Study to Learn Whether There Are Differences in the Kidney's Ability to Work Properly in Korean Patients With Non-valvular Atrial Fibrillation (Irregular and Often Rapid Heartbeat Not Caused by a Heart Valve Problem) Treated With Rivaroxaban as Compared to Those Treated With Warfarin (RENOVATOR)

RENal Outcomes of Rivaroxaban Compared With Warfarin in Asian patienTs With nOn-valvular atRial Fibrillation: a Nationwide Population-based Study

This is an observational study in which data collected from the past of patients with non-valvular atrial fibrillation (NVAF) is studied.

NVAF is a condition in which patients suffer from irregular and often rapid heartbeats which are not caused by a heart valve problem. NVAF can lead to thromboembolism, a condition that happens when a blood clot forms in the body and travels through the blood stream to plug another vessel. To prevent thromboembolism doctors often prescribe a blood thinner medication.

In patients with NVAF that receive a blood thinner, it is common that the kidneys' ability to work properly, also called the kidney function, decreases. This may increase the risk of stroke, a condition which occurs when a vessel supplying blood to the brain is blocked and the risk of bleeding. It is therefore important to maintain the kidneys' ability to work properly in these patients who are treated with blood thinners.

In the beginning, only one blood thinner that could be given as a tablet by mouth was available. This blood thinner was called warfarin. Over the years, further medications have become available, for example dabigatran or rivaroxaban. There is some evidence that a decrease of the kidney function is more common with warfarin than with dabigatran or rivaroxaban. For other similar new treatments however, evidence is missing or conflicting. There also could be other relevant factors such as the kidney function before the start of treatment or the patient's genes/origin.

In this study researchers want to collect more data to compare two different blood thinner medications, rivaroxaban and warfarin. The main goal is to see whether there is a difference between the two treatments regarding the kidneys' ability to work properly. To find this out, the researchers will compare the number of patients in each group who developed chronic kidney disease stage 5 (close to or corresponding to chronic kidney failure), had a kidney transplant or needed to undergo long term dialysis. In addition, data is collected and compared about the patients' age, gender, weight, height and whether they had other related medical problems.

This study will collect information from the health records from the Korean National Health Insurance Corporation (NHIC) database. Besides this data collection, no further tests or examinations are planned in this study. Researchers will look at the health information from adult men and women in Korea who were diagnosed with NVAF between January 2013 and December 2017. They will study data of the patients who did not receive any medication with blood thinners in past 24 months before starting rivaroxaban and warfarin treatment between January 2015 and December 2017. They will follow up all the participants until December 2018.

Study Overview

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

• Study Type: Observational
• Enrollment (Actual): 45000

Contacts and Locations

Study Locations

• Korea, Republic of
  • Multiple Locations, Korea, Republic of
    • Many locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study is conducted using administrative claims data of the Korean National Health Insurance Service (NHIS) and the linked health check-up database of the National Health Insurance Corporation (NHIC) between 2013 to 2018.

Description

Inclusion Criteria:

• Be ≥20 years of age (legal age in Korea) at the time of anticoagulation initiation
• Have a diagnosis of NVAF (in the 24-months prior to index date)
• Have no record of OAC use (in the 24-months prior to index date)
• Newly initiated on rivaroxaban or warfarin (index date)

Exclusion Criteria:

• Who have end-stage renal disease or are on dialysis (in the 12-months prior to index date)
• With evidence of valvular heart disease (in the 12-months prior to index date)
• With pulmonary embolism or deep vein thrombosis (within 6 months before index date)
• Who received joint replacement (within 6 months before diagnosis)
• Patients who had previous OAC prescription between 2013 and 2014
• With rivaroxaban doses other than 15 or 20 mg once daily

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants treated with rivaroxaban; NVAF patients who were OAC-naïve (Have no record of Oral anticoagulation [OAC] therapy use in the January 2013 to December 2014) and newly initiated on rivaroxaban (defined as the index date) during the enrollment period from January 2015 to December 2017.	Drug: Rivaroxaban (Xarelto, BAY59-7939); One of NOAC (Non-vitamin K antagonist oral anticoagulants)
Participants treated with warfarin; NVAF patients who were OAC-naïve (Have no record of Oral anticoagulation [OAC] therapy use in the January 2013 to December 2014) and newly initiated on warfarin (defined as the index date) during the enrollment period from January 2015 to December 2017.	Drug: Warfarin; One of OAC (Oral anticoagulation therapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of kidney failure	Kidney failure is defined as progression to stage 5 chronic kidney disease (CKD), the need for maintenance dialysis, or having a kidney transplant	Retrospective analysis from 01-Jan-2015 to 31-Dec-2018

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ≥ 30% decline in estimated glomerular filtration rate (eGFR)		Retrospective analysis from 01-Jan-2015 to 31-Dec-2018
Number of participants with doubling of the serum creatinine level		Retrospective analysis from 01-Jan-2015 to 31-Dec-2018
Incidence of Acute kidney injury (AKI)	AKI is defined as an emergency department visit or hospitalization with a diagnostic code of AKI	Retrospective analysis from 01-Jan-2015 to 31-Dec-2018
Number of participants with composite renal outcome of ≥ 30% decline in eGFR, doubling of the serum creatinine level and kidney failure		Retrospective analysis from 01-Jan-2015 to 31-Dec-2018

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here for access to information about Bayer's transparency standards and Bayer studies.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 22, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; Rivaroxaban; Systemic embolism; Non-valvular atrial fibrillation (NVAF)
• 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; Rivaroxaban; Warfarin
• Other Study ID Numbers: 21615

Plan for Individual participant data (IPD)

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

IPD Plan Description

Availability of this study's data will later 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.vivli.org 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 member 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