Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation

NCT ID: NCT02942407

Last Updated: 2020-12-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2019-08-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a prospective, randomized, open-label, blinded end-point evaluation trial. The patient population consists of patients on hemodialysis who have atrial fibrillation (AF) and end-stage renal disease (ESRD) .

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a multicenter study in adult patients with AF and ESRD who are on hemodialysis and who have stroke risk factors making them candidates for oral anticoagulation. Patients will be randomized to apixaban versus warfarin, and will be treated for up to 15 months.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Atrial Fibrillation End Stage Renal Disease

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Renal dialysis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

apixaban

apixaban 5 mg twice daily (apixaban 2.5 mg twice daily for selected patients)

Group Type EXPERIMENTAL

apixaban

Intervention Type DRUG

oral anticoagulant

warfarin

warfarin daily dose adjusted to target International Normalized Ration(INR) of 2-3

Group Type EXPERIMENTAL

warfarin

Intervention Type DRUG

oral anticoagulant

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

apixaban

oral anticoagulant

Intervention Type DRUG

warfarin

oral anticoagulant

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Eliquis Coumadin Jantoven

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Males and females, age at least 18 years, or the local age of consent, whichever is greater.
* Patients with AF defined as AF on ECG at enrollment or two or more reports of AF from separate monitoring events at least 2 weeks apart (report of ECG, Holter monitor, event monitor or implantable loop recorder).
* CHA2DS2-VASc score of ≥ 2.
* End-stage renal disease treated with hemodialysis for ≥ 3 months.
* Considered by the treating physician(s) to be candidate for oral anticoagulation.
* If of childbearing potential, be willing to avoid pregnancy during the study.

Exclusion Criteria

* Not considered by the treating physician(s) to be candidates for oral anticoagulation (for example, hemoglobin \< 8.5g/dL, history of intracranial hemorrhage, active bleeding, recent gastrointestinal bleed or retroperitoneal bleed, severe hepatic impairment, or anaphylactic reaction to apixaban)
* Moderate or severe mitral stenosis
* Conditions other than AF that require anticoagulation such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism
* Need for aspirin at a dose \> 81 mg a day or need for P2Y12 antagonist therapy (for example clopidogrel, prasugrel, or ticagrelor)
* Life expectancy \< 3 months
* Anticipated kidney transplant within the next 3 months
* Prisoners or others who are involuntarily incarcerated or detained
* Pregnant, breastfeeding, or considering pregnancy.
* Participation in a clinical trial of an experimental treatment within the past 30 days
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Christopher Granger, MD

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Christopher Granger, MD

Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Christopher Granger, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Glenn Chertow, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Nephrology Consultants

Huntsville, Alabama, United States

Site Status

The Medical Research Group, Inc.

Fresno, California, United States

Site Status

DaVita Clinical Trials, LLC

Long Beach, California, United States

Site Status

Southland Renal Medical Group

Long Beach, California, United States

Site Status

Valley Renal Medical Group Research

Northridge, California, United States

Site Status

Summit Nephrology Medical Group, Inc.

Roseville, California, United States

Site Status

Satellite Healthcare

San Jose, California, United States

Site Status

Washington Nephrology Associates

Washington D.C., District of Columbia, United States

Site Status

South Florida Nephrology Group PA, Research Division

Coral Springs, Florida, United States

Site Status

LG. Diagnostic, Inc. & Cosmetic Center

Miami, Florida, United States

Site Status

Nuren Medical and Research Center

Miami, Florida, United States

Site Status

Medical Professional Clinical Research Center

Miami, Florida, United States

Site Status

Boise Kidney and Hypertension Institute

Meridian, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

NANI Research

Crystal Lake, Illinois, United States

Site Status

NANI Research

River Forest, Illinois, United States

Site Status

NANI Research

Fort Wayne, Indiana, United States

Site Status

Northwest Louisiana Nephrology

Shreveport, Louisiana, United States

Site Status

Anne Arundel Medical Center

Annapolis, Maryland, United States

Site Status

The Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Washington Nephrology Associates

Takoma Park, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

South Shore Nephrology

Plymouth, Massachusetts, United States

Site Status

Renal and Transplant Associates of New England

Springfield, Massachusetts, United States

Site Status

Paragon Health Neprhology Centre

Kalamazoo, Michigan, United States

Site Status

St. Clair Nephrology

Port Huron, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Southwest Mississippi Nephrology, PLLC

Brookhaven, Mississippi, United States

Site Status

Southern Clinical Research Group, LLC

Gulfport, Mississippi, United States

Site Status

Nephrology & Hypertension Associates

Tupelo, Mississippi, United States

Site Status

Polack Renal, LLC

St Louis, Missouri, United States

Site Status

Sierra Nevada Nephrology Consultants

Reno, Nevada, United States

Site Status

Renal Medicine Associates

Albuquerque, New Mexico, United States

Site Status

Advanced Kidney Care of Hudson Valley

Poughkeepsie, New York, United States

Site Status

Durham Nephrology Associates

Durham, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Eastern Nephrology Associates, PLLC.

Kinston, North Carolina, United States

Site Status

Eastern Nephrology Associates, PLLC

New Bern, North Carolina, United States

Site Status

HNC Dialysis, Ltd.

Columbus, Ohio, United States

Site Status

Northeast Clinical Research Ctr

Bethlehem, Pennsylvania, United States

Site Status

Penn State Health - Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Columbia Nephrology Associates

Columbia, South Carolina, United States

Site Status

South Carolina Nephrology and Hypertension

Orangeburg, South Carolina, United States

Site Status

Sumter Medical Specialists

Sumter, South Carolina, United States

Site Status

Regional Health Clinical Research

Rapid City, South Dakota, United States

Site Status

Knoxville Kidney Center

Knoxville, Tennessee, United States

Site Status

Southwest Houston Research, Ltd.

Houston, Texas, United States

Site Status

Lubbock Vascular Access Center

Lubbock, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Washington Nephrology Associates

Alexandria, Virginia, United States

Site Status

University of Virgina Health System

Charlottesville, Virginia, United States

Site Status

TPMG Clinical Research

Newport News, Virginia, United States

Site Status

Valley Nephrology Associates

Roanoke, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Nephrology and Hypertension Associates

Bluefield, West Virginia, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Aspirius Research Institute

Wausau, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Wizemann V, Tong L, Satayathum S, Disney A, Akiba T, Fissell RB, Kerr PG, Young EW, Robinson BM. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int. 2010 Jun;77(12):1098-106. doi: 10.1038/ki.2009.477. Epub 2010 Jan 6.

Reference Type BACKGROUND
PMID: 20054291 (View on PubMed)

Olesen JB, Lip GY, Kamper AL, Hommel K, Kober L, Lane DA, Lindhardsen J, Gislason GH, Torp-Pedersen C. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012 Aug 16;367(7):625-35. doi: 10.1056/NEJMoa1105594.

Reference Type BACKGROUND
PMID: 22894575 (View on PubMed)

Nigwekar SU, Bhan I, Turchin A, Skentzos SC, Hajhosseiny R, Steele D, Nazarian RM, Wenger J, Parikh S, Karumanchi A, Thadhani R. Statin use and calcific uremic arteriolopathy: a matched case-control study. Am J Nephrol. 2013;37(4):325-32. doi: 10.1159/000348806. Epub 2013 Mar 21.

Reference Type BACKGROUND
PMID: 23548843 (View on PubMed)

Yang F, Chou D, Schweitzer P, Hanon S. Warfarin in haemodialysis patients with atrial fibrillation: what benefit? Europace. 2010 Dec;12(12):1666-72. doi: 10.1093/europace/euq387. Epub 2010 Nov 2.

Reference Type BACKGROUND
PMID: 21045011 (View on PubMed)

Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009 Oct;20(10):2223-33. doi: 10.1681/ASN.2009030319. Epub 2009 Aug 27.

Reference Type BACKGROUND
PMID: 19713308 (View on PubMed)

Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Humphries KH, Tu JV, Behlouli H, Guo H, Pilote L. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014 Mar 18;129(11):1196-203. doi: 10.1161/CIRCULATIONAHA.113.004777. Epub 2014 Jan 22.

Reference Type BACKGROUND
PMID: 24452752 (View on PubMed)

Granger CB, Chertow GM. A pint of sweat will save a gallon of blood: a call for randomized trials of anticoagulation in end-stage renal disease. Circulation. 2014 Mar 18;129(11):1190-2. doi: 10.1161/CIRCULATIONAHA.113.007549. Epub 2014 Jan 22. No abstract available.

Reference Type BACKGROUND
PMID: 24452751 (View on PubMed)

Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW. Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation. 2015 Mar 17;131(11):972-9. doi: 10.1161/CIRCULATIONAHA.114.014113. Epub 2015 Jan 16.

Reference Type BACKGROUND
PMID: 25595139 (View on PubMed)

Hart RG, Pearce LA, Asinger RW, Herzog CA. Warfarin in atrial fibrillation patients with moderate chronic kidney disease. Clin J Am Soc Nephrol. 2011 Nov;6(11):2599-604. doi: 10.2215/CJN.02400311. Epub 2011 Sep 8.

Reference Type BACKGROUND
PMID: 21903982 (View on PubMed)

Reinecke H, Brand E, Mesters R, Schabitz WR, Fisher M, Pavenstadt H, Breithardt G. Dilemmas in the management of atrial fibrillation in chronic kidney disease. J Am Soc Nephrol. 2009 Apr;20(4):705-11. doi: 10.1681/ASN.2007111207. Epub 2008 Dec 17.

Reference Type BACKGROUND
PMID: 19092127 (View on PubMed)

Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007 Jun 19;146(12):857-67. doi: 10.7326/0003-4819-146-12-200706190-00007.

Reference Type BACKGROUND
PMID: 17577005 (View on PubMed)

Winkelmayer WC, Liu J, Setoguchi S, Choudhry NK. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol. 2011 Nov;6(11):2662-8. doi: 10.2215/CJN.04550511. Epub 2011 Sep 29.

Reference Type BACKGROUND
PMID: 21959598 (View on PubMed)

Hohnloser SH, Hijazi Z, Thomas L, Alexander JH, Amerena J, Hanna M, Keltai M, Lanas F, Lopes RD, Lopez-Sendon J, Granger CB, Wallentin L. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2012 Nov;33(22):2821-30. doi: 10.1093/eurheartj/ehs274. Epub 2012 Aug 29.

Reference Type BACKGROUND
PMID: 22933567 (View on PubMed)

Elliott MJ, Zimmerman D, Holden RM. Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. Am J Kidney Dis. 2007 Sep;50(3):433-40. doi: 10.1053/j.ajkd.2007.06.017.

Reference Type BACKGROUND
PMID: 17720522 (View on PubMed)

Wu JR, DeWalt DA, Baker DW, Schillinger D, Ruo B, Bibbins-Domingo K, Macabasco-O'Connell A, Holmes GM, Broucksou KA, Erman B, Hawk V, Cene CW, Jones CD, Pignone M. A single-item self-report medication adherence question predicts hospitalisation and death in patients with heart failure. J Clin Nurs. 2014 Sep;23(17-18):2554-64. doi: 10.1111/jocn.12471. Epub 2013 Dec 20.

Reference Type BACKGROUND
PMID: 24355060 (View on PubMed)

Gonzalez JS, Schneider HE, Wexler DJ, Psaros C, Delahanty LM, Cagliero E, Safren SA. Validity of medication adherence self-reports in adults with type 2 diabetes. Diabetes Care. 2013 Apr;36(4):831-7. doi: 10.2337/dc12-0410. Epub 2012 Nov 30.

Reference Type BACKGROUND
PMID: 23204245 (View on PubMed)

Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, Granger CB, Hanna M, Held C, Husted S, Hylek EM, Jansky P, Lopes RD, Ruzyllo W, Thomas L, Wallentin L. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014 Jul 21;35(28):1864-72. doi: 10.1093/eurheartj/ehu046. Epub 2014 Feb 20.

Reference Type BACKGROUND
PMID: 24561548 (View on PubMed)

Fox KA, Piccini JP, Wojdyla D, Becker RC, Halperin JL, Nessel CC, Paolini JF, Hankey GJ, Mahaffey KW, Patel MR, Singer DE, Califf RM. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J. 2011 Oct;32(19):2387-94. doi: 10.1093/eurheartj/ehr342. Epub 2011 Aug 28.

Reference Type BACKGROUND
PMID: 21873708 (View on PubMed)

Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med. 1990 Dec;9(12):1447-54. doi: 10.1002/sim.4780091208.

Reference Type BACKGROUND
PMID: 2281232 (View on PubMed)

Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O'Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011 Mar 3;364(9):806-17. doi: 10.1056/NEJMoa1007432. Epub 2011 Feb 10.

Reference Type BACKGROUND
PMID: 21309657 (View on PubMed)

Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.

Reference Type BACKGROUND
PMID: 21870978 (View on PubMed)

Herzog CA, Asinger RW, Berger AK, Charytan DM, Diez J, Hart RG, Eckardt KU, Kasiske BL, McCullough PA, Passman RS, DeLoach SS, Pun PH, Ritz E. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011 Sep;80(6):572-86. doi: 10.1038/ki.2011.223. Epub 2011 Jul 13.

Reference Type BACKGROUND
PMID: 21750584 (View on PubMed)

Pokorney SD, Chertow GM, Al-Khalidi HR, Gallup D, Dignacco P, Mussina K, Bansal N, Gadegbeku CA, Garcia DA, Garonzik S, Lopes RD, Mahaffey KW, Matsuda K, Middleton JP, Rymer JA, Sands GH, Thadhani R, Thomas KL, Washam JB, Winkelmayer WC, Granger CB; RENAL-AF Investigators. Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial. Circulation. 2022 Dec 6;146(23):1735-1745. doi: 10.1161/CIRCULATIONAHA.121.054990. Epub 2022 Nov 6.

Reference Type DERIVED
PMID: 36335914 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.usrds.org/adr.aspx

United States Renal Data System Web Site

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Pro00068545

Identifier Type: -

Identifier Source: org_study_id