Anticoagulation Strategies for Acute Venous Thromboembolism in Patients With End-Stage Renal Disease Using USRDS Data

• ClinicalTrials.gov Identifier: NCT04818151
• Recruitment Status: Completed
• First Posted: March 26, 2021
• Last Update Posted: July 26, 2021
• Sponsor: Johns Hopkins University
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

Patients with end stage renal disease (ESRD) are at significantly increased risk of thrombosis and bleeding relative to those with normal renal function which makes anticoagulation particularly challenging. Further, ESRD patients undergoing initiation of anticoagulation for acute VTE are often kept in the hospital for heparin "bridging" which may lead to a protracted length-of-stay (LOS) and may place patients at risk for hospital-associated complications. The advent of direct oral anticoagulants (DOACs) has offered physicians choices in the management of venous thromboembolism (VTE). However, evidence suggests that rivaroxaban and dabigatran are associated with a higher risk of bleeding in ESRD patients. In contrast, research suggests that apixaban may be safer in patients with ESRD, and recent evidence suggests lower bleeding rates in ESRD patients treated for atrial fibrillation with apixaban compared to those treated with warfarin. However, to date, no large national cohort studies have examined the safety, effectiveness, and healthcare utilization of apixaban in patients with ESRD who have acute VTE. The investigators propose to use the Standard Analytic Files from the United States Renal Data System (USRDS) for years 2014 through 2018 to evaluate the safety, effectiveness, and healthcare utilization of ESRD patients initiated on apixaban compared to those initiated on warfarin (following heparin) to treat acute VTE.

Condition or disease	Intervention/treatment
Venous Thromboembolic Disease; Kidney Failure, Chronic	Drug: Warfarin; Drug: Apixaban

Detailed Description:

The investigators will perform a retrospective cohort analysis using USRDS data from 2014 through 2018 and a descriptive serial cross-sectional analysis using USRDS data from 2009 through 2018 to evaluate the investigators' aims. USRDS data will be utilized to address all the research aims.

Primary Objective To compare rates of major bleeding attributable to initiation of treatment with apixaban relative to warfarin among patients with ESRD and acute VTE The primary safety outcome will be rates of major bleeding within 6 months of VTE diagnosis as defined by Cunningham, which is a standardized definition of major bleeding that can be derived from administrative data and is based on clinical bleeding definitions from a number of clinical trials. A secondary safety outcome will be gastrointestinal bleeding within 6 months of VTE diagnosis.

Secondary Objectives To describe contemporary anticoagulation strategies to treat acute VTE in ESRD patients and changes over the last decade The investigators will report rates of use of anticoagulation strategies [warfarin, low molecular weight heparin (LMWH), and DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran)] in this ESRD population. The investigators will examine rates of these strategies by year to examine changes in adoption of various strategies over time as DOACs have become available for VTE treatment.

To compare rates of recurrent VTE attributable to initiation of treatment with apixaban relative to warfarin among patients with ESRD and acute VTE The primary outcome will be recurrent VTE within 6 months of VTE diagnosis. All-cause mortality within 6 months of VTE diagnosis will be evaluated as an exploratory endpoint.

To compare healthcare resource utilization from 15 days before to 90 days after first prescription date attributable to initiation of treatment with apixaban relative to warfarin among patients with ESRD and acute VTE The primary outcome will be total inpatient days from 15 days before to 90 days after first prescription date. In addition to total inpatient days, the investigators will also compare emergency department (ED) utilization after initiation of anticoagulation across treatment strategies. By incorporating 15 days prior to first prescription date, the investigators will capture hospitalization days that were associated with the index VTE diagnosis, given that the first anticoagulation prescription would likely be written at the time of hospital discharge for those patients who are hospitalized.

Study Design

• Study Type: Observational
• Actual Enrollment: 14914 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Anticoagulation Strategies for the Treatment of Acute Venous Thromboembolism in Medicare Fee For-Service Patients With End-Stage Renal Disease Using USRDS Data
• Actual Study Start Date: January 1, 2021
• Actual Primary Completion Date: June 30, 2021
• Actual Study Completion Date: June 30, 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
ESRD patients with VTE treated with warfarin; Warfarin as primary treatment of VTE	Drug: Warfarin; Warfarin treatment for VTE
ESRD patients with VTE treated with apixaban; Apixaban as primary treatment of VTE	Drug: Apixaban; Apixaban treatment for VTE

Outcome Measures

Primary Outcome Measures :

1. Bleeding occurrence [ Time Frame: 3 months ]
   Number of bleeding occurrences.
2. Recurrent thrombosis occurrence [ Time Frame: 3 months ]
   Number of recurrent thrombosis occurrences.

Secondary Outcome Measures :

1. Days in acute care [ Time Frame: 3 months ]
   Number of hospital days/ED utilization.

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

All patients in USRDS dataset from 2009-2018 with ESRD and VTE

Criteria

Inclusion Criteria:

• ESRD on dialysis with acute VTE

Exclusion Criteria:

• Anticoagulation for non-VTE indication

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Bristol-Myers Squibb

Investigators

• Principal Investigator: Daniel J Brotman, MD; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT04818151
• Other Study ID Numbers: IRB00272929; CV185-804 ( Other Grant/Funding Number: Bristol Myers Squibb )
• First Posted: March 26, 2021
• Last Update Posted: July 26, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Johns Hopkins University:

Anticoagulation; Apixaban; Warfarin; Heparin; Bleeding; Hemodialysis

Additional relevant MeSH terms:

Kidney Failure, Chronic; Renal Insufficiency; Thromboembolism; Venous Thromboembolism; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Warfarin; Apixaban; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action