Rivaroxaban vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation

NCT ID: NCT03702582

Last Updated: 2023-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-30

Study Completion Date

2023-10-01

Brief Summary

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This prospective, randomized, active-controlled, parallel arm study compares the safety and financial benefits of arterial thromboembolism prophylaxis with Warfarin vs. Rivaroxaban (A novel oral anticoagulant) in patients with new onset atrial fibrillation after sternotomy for cardiac operations.

Detailed Description

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New onset atrial fibrillation (NOAF) is a common occurrence following cardiac surgery, occurring in 20-30% of patients post-operatively. Historically, Vitamin K antagonist therapy with Warfarin has been the treatment of choice for prophylaxis against stroke and systemic arterial thromboembolism in NOAF. Warfarin inhibits the Vitamin K dependent factors involved in both the intrinsic and extrinsic coagulation cascades, thus decreasing systemic clotting. However, Warfarin therapy comes with many challenges including prolonged titration, tedious monitoring requirements and in some cases, increased bleeding risk.

The limitations associated with Warfarin may be mitigated by using new oral anticoagulants (NOACs) like Rivaroxaban which have no routine monitoring requirements. Rivaroxaban is a direct inhibitor of Factor Xa, a central reactant in both the intrinsic and extrinsic coagulation cascades. Studies in non-operative patients with atrial fibrillation have shown that Rivaroxaban is non-inferior to Warfarin for stroke prophylaxis with similar risk profiles. This study aims to compare the efficacy, safety and financial cost of these two drugs when used for the management of new onset atrial fibrillation that occurs after cardiac operations.

Conditions

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Atrial Fibrillation Stroke Bleeding

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Cardiac surgery patients who meet study criteria and develop recurrent or persistent atrial fibrillation post-operatively will be randomized 1:1 to receive Warfarin or Rivaroxaban for prophylaxis against stroke or other systemic arterial embolism
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Statisticians performing comparative analyses of primary outcomes will be blinded as to the allocation designations of patients. Otherwise there will be no masking in the study.

Study Groups

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Rivaroxaban

Rivaroxaban: Direct inhibitor of Factor Xa, an enzyme that stimulates the formation of thrombin from prothrombin (A critical step in both the intrinsic and extrinsic aspects of the coagulation cascade)

Dosage form: Per Os (Oral)

Dosage and Frequency: 20 mg every evening with the evening meal (No titration requirements). For patients with decreased glomerular filtration rate (GFR between 15 ml/min and 50 ml/min), dosing will be decreased to 15 mg every evening with the evening meal.

Duration: 30 days (Possibility of continuation after post-operative cardiology clinic visit)

Group Type EXPERIMENTAL

Rivaroxaban

Intervention Type DRUG

Anticoagulant drug that works via direct inhibition of factor Xa. FDA approved for prophylaxis against stroke in non-valvular atrial fibrillation

Warfarin

Warfarin: Competitive inhibitor of vitamin K epoxide reductase complex 1, an important enzyme in the activation pathway for vitamin K dependent coagulation factors

Dosage form: Per Os (Oral)

Dosage and Frequency: Initial dose of 2 - 5 mg nightly after the evening meal (QHS) with appropriate titration to goal INR 2.0 - 3.0 (Initial dose based on weight, age, gender, co-morbidities and concurrent medications). INR will be checked daily to weekly depending on stability of dosing and medication regimen.

Duration: 30 days (Possibility of continuation after post-operative Cardiology clinic visit)

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

Anticoagulation drug that works via inhibition of vitamin K dependent clotting factors. FDA approved for prophylaxis against stroke in atrial fibrillation

Interventions

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Rivaroxaban

Anticoagulant drug that works via direct inhibition of factor Xa. FDA approved for prophylaxis against stroke in non-valvular atrial fibrillation

Intervention Type DRUG

Warfarin

Anticoagulation drug that works via inhibition of vitamin K dependent clotting factors. FDA approved for prophylaxis against stroke in atrial fibrillation

Intervention Type DRUG

Other Intervention Names

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Xarelto Database of Molecules (PubChem CID): 6433119 Coumadin Database of Molecules (PubChem CID): 54678486

Eligibility Criteria

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Inclusion Criteria

* Male or Female ≥ 18 years
* At least one of the following procedures: coronary artery bypass grafting, aortic valve repair, mitral valve repair, non-mechanical aortic valve replacement, any combination of these procedures
* Two or more episodes of New Onset Atrial Fibrillation (each lasting \> 20 minutes) or persistent atrial fibrillation lasting \> 24 hours (Or for \>18 hours over a 24-hour interval)
* If female of child-bearing age, use of adequate contraception

Exclusion Criteria

* Pre-existing paroxysmal atrial fibrillation before cardiac surgery
* Pre-existing indications for therapeutic anticoagulation (Including but not limited to PE, DVT, mechanical valve)
* Moderate-to-severe mitral valve stenosis not surgically corrected
* Pre-existing allergy to study medications
* Recent (\< 1 year) or ongoing pregnancy (Urine pregnancy test will be obtained for women of child bearing age at the time of enrollment into the study)
* Stroke within 1 month prior to surgery or postoperatively prior to initiation of study drugs
* Postoperative bleeding episode prior to initiation of study drug
* Severe dysfunction of another organ system including GFR \< 30 ml/min, baseline INR \> 1.7, ileus or other gastrointestinal pathology hindering ability to absorb oral medications, and known coagulation pathway deficiencies
* Postoperative need for non-aspirin anti-platelet therapy that cannot be discontinued when therapeutic anticoagulation is initiated
* Patient taking medications with known major interactions with study drugs with no therapeutic alternatives)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Asishana A Osho

Clinical Fellow in Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Asishana A Osho, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Thoralf M Sundt, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. doi: 10.1056/NEJMoa1805090. Epub 2018 Aug 26.

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Butt JH, Xian Y, Peterson ED, Olsen PS, Rorth R, Gundlund A, Olesen JB, Gislason GH, Torp-Pedersen C, Kober L, Fosbol EL. Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery and Patients With Nonvalvular Atrial Fibrillation. JAMA Cardiol. 2018 May 1;3(5):417-424. doi: 10.1001/jamacardio.2018.0405.

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Charlton B, Adeboyeje G, Barron JJ, Grady D, Shin J, Redberg RF. Length of hospitalization and mortality for bleeding during treatment with warfarin, dabigatran, or rivaroxaban. PLoS One. 2018 Mar 28;13(3):e0193912. doi: 10.1371/journal.pone.0193912. eCollection 2018.

Reference Type BACKGROUND
PMID: 29590141 (View on PubMed)

Megens MR, Churilov L, Thijs V. New-Onset Atrial Fibrillation After Coronary Artery Bypass Graft and Long-Term Risk of Stroke: A Meta-Analysis. J Am Heart Assoc. 2017 Dec 22;6(12):e007558. doi: 10.1161/JAHA.117.007558.

Reference Type BACKGROUND
PMID: 29273637 (View on PubMed)

Hawks MK, Bryce C. Rivaroxaban vs. Warfarin for Anticoagulation in Patients with Atrial Fibrillation Undergoing Ablation and Cardioversion. Am Fam Physician. 2016 Oct 1;94(7):Online. No abstract available.

Reference Type BACKGROUND
PMID: 27929207 (View on PubMed)

Gillinov AM, Bagiella E, Moskowitz AJ, Raiten JM, Groh MA, Bowdish ME, Ailawadi G, Kirkwood KA, Perrault LP, Parides MK, Smith RL 2nd, Kern JA, Dussault G, Hackmann AE, Jeffries NO, Miller MA, Taddei-Peters WC, Rose EA, Weisel RD, Williams DL, Mangusan RF, Argenziano M, Moquete EG, O'Sullivan KL, Pellerin M, Shah KJ, Gammie JS, Mayer ML, Voisine P, Gelijns AC, O'Gara PT, Mack MJ; CTSN. Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery. N Engl J Med. 2016 May 19;374(20):1911-21. doi: 10.1056/NEJMoa1602002. Epub 2016 Apr 4.

Reference Type BACKGROUND
PMID: 27043047 (View on PubMed)

Anderson E, Johnke K, Leedahl D, Glogoza M, Newman R, Dyke C. Novel oral anticoagulants vs warfarin for the management of postoperative atrial fibrillation: clinical outcomes and cost analysis. Am J Surg. 2015 Dec;210(6):1095-102; discussion 1102-3. doi: 10.1016/j.amjsurg.2015.07.005. Epub 2015 Sep 18.

Reference Type BACKGROUND
PMID: 26482512 (View on PubMed)

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

Reference Type BACKGROUND
PMID: 24251359 (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)

Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.

Reference Type BACKGROUND
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Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.

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Osho AA, Moonsamy P, Ethridge BR, Leya GA, D'Alessandro DA, Jassar AS, Villavicencio MA, Melnitchouk SI, Tolis G, Langer NB, Funamoto M, Li SS, Colon KM, Mohan N, Locascio JJ, Lubitz SA, Akeju O, Sundt TM. Rationale and Design of the Randomized Controlled Trial of New Oral Anticoagulants Versus Warfarin for Post Cardiac Surgery Atrial Fibrillation: The NEW-AF Trial. Ann Surg. 2022 Jul 1;276(1):200-204. doi: 10.1097/SLA.0000000000004459. Epub 2020 Sep 1.

Reference Type DERIVED
PMID: 32889881 (View on PubMed)

Other Identifiers

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2018P002307

Identifier Type: -

Identifier Source: org_study_id

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