Rivaroxaban vs. Warfarin for Post Cardiac Surgery Atrial Fibrillation

NCT03702582 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 2018P002307
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation; Stroke; Bleeding

Keywords

Atrial Fibrillation; Rivaroxaban; Warfarin; Stroke; Anticoagulation; Bleeding

Outcome Measures

Primary Outcomes (1)

• Postoperative Length of Stay

  Length of inpatient stay in days from time of departure from the operating room

  Up to 6 months following the cardiac operation

Secondary Outcomes (8)

• Episode of Major Bleeding (Defined as the Occurrence of Any of Several Events Listed in the Description. No Specific Scale, Questionnaire or Instrument Will be Used)

  Up to 30 days after discharge from the initial postoperative hospitalization

• Cerebrovascular Accident (CVA)

  Up to 30 days after discharge from the initial postoperative hospitalization

• Other Systemic Embolism

  Up to 30 days after discharge from the initial postoperative hospitalization

• Deep Venous Thrombosis (DVT) and/or Pulmonary Embolism (PE)

  Up to 30 days after discharge from the initial postoperative hospitalization

• Minor Bleeding

  Up to 30 days after discharge from the initial postoperative hospitalization

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

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)

Drug: Rivaroxaban

Warfarin

ACTIVE COMPARATOR

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)

Drug: Warfarin

Interventions

Rivaroxaban DRUG

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

Also known as: Xarelto, Database of Molecules (PubChem CID): 6433119

Rivaroxaban

Warfarin DRUG

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

Also known as: Coumadin, Database of Molecules (PubChem CID): 54678486

Warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (12)

• 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.

  PMID: 30145946 BACKGROUND

• 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.

  PMID: 29590304 BACKGROUND

• 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.

  PMID: 29590141 BACKGROUND

• 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.

  PMID: 29273637 BACKGROUND

• 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.

  PMID: 27929207 BACKGROUND

• 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.

  PMID: 27043047 BACKGROUND

• 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.

  PMID: 26482512 BACKGROUND

• 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.

  PMID: 24251359 BACKGROUND

• 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.

  PMID: 21870978 BACKGROUND

• 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.

  PMID: 21830957 BACKGROUND

• 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.

  PMID: 19717844 BACKGROUND

• 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.

  PMID: 32889881 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Stroke; Hemorrhage

Interventions

Rivaroxaban; Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Early trial termination reduced the ability of the study to detect differences in primary and secondary outcomes. In addition, the trial was underpowered to detect rare safety events, such as thromboembolic complications, and the short 30-day follow-up period restricts conclusions about long-term outcomes, including recurrent AF and adherence.

Results Point of Contact

• Title: Asishana Osho, MD
• Organization: Massachusetts General Hospital

Asishana.Osho@MGH.HARVARD.EDU

6177246319

Study Officials

• Asishana A Osho, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Thoralf M Sundt, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Fellow in Surgery

Model Details: 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

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 11, 2018
• Study Start: April 30, 2019
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: May 19, 2026
• Results First Posted: May 19, 2026

Record last verified: 2026-04

Locations

US (1)