NCT02283294

Brief Summary

The purpose of this study is to evaluate if Apixaban will decrease the complication of having another stroke for people who have atrial fibrillation if initiated earlier than standard of care.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
91

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Apr 2015

Typical duration for phase_3

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 29, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 5, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2019

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

November 30, 2021

Completed
Last Updated

November 30, 2021

Status Verified

December 1, 2018

Enrollment Period

4.2 years

First QC Date

October 29, 2014

Results QC Date

July 7, 2021

Last Update Submit

November 3, 2021

Conditions

Transient Ischemic AttackStrokeAtrial Fibrillation

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With a Composite Endpoint of Fatal Stroke, Recurrent Ischemic Stroke, or TIA

    180 days

Secondary Outcomes (1)

  • Number of Participants With an Intracranial Hemorrhage Assessed by MRI/CT

    180 days

Study Arms (2)

Apixaban

EXPERIMENTAL

Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively

Drug: Apixaban

Warfarin

ACTIVE COMPARATOR

standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke).

Drug: Warfarin

Interventions

ApixabanDRUG
Apixaban
WarfarinDRUG
Warfarin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Signed Written Informed Consent
  • Males and Females over 18 years of age.
  • History of Nonvalvular Atrial Fibrillation (NVAF) by documentation in the medical history or newly diagnosed nonvalvular Atrial Fibrillation at time of study randomization by ECG, device or telemetry .
  • Diagnosis of TIA or small or medium ischemic stroke 0 to 48 hours from signs or symptoms.
  • Women of child-bearing potential must use a reliable method of contraception and must provide a negative pregnancy test at entry into the study and within 24 hours of study treatment initiation.
  • WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug Apixaban plus 5 half-lives (approximately 3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion.
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with Apixaban plus 5 half-lives (approximately 3 days) plus 90 days (duration of sperm turnover) for a total of 93 days post-treatment completion.
  • Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing as described in this section.
  • Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of \< 1% when used consistently and correctly.
  • At a minimum, subjects must agree to the use of one method of highly effective contraception as listed below:
  • HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
  • Male condoms with spermicide
  • Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subject's WOCBP partner. Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug
  • IUDs, such as ParaGard™
  • Tubal ligation
  • +2 more criteria

You may not qualify if:

  • Hemorrhagic stroke
  • Large ischemic stroke
  • History of major bleeding within the last 6 months from time of subject enrollment (e.g. GI bleed).
  • History of intracranial bleed
  • Current or history of bleeding disorders (e.g. blood dycrasias)
  • Blood Pressure of 180/100 mmHg on hypertensive therapy day of randomization per PI discretion 20.
  • Current illicit drug use and/or chronic alcohol use per PI discretion.
  • Severe liver disease (AST/ALT 2x upper limit).
  • Patients with kidney disease meeting criteria to take 2.5 mg twice daily who are taking strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin) .
  • Any other suspected etiology for stroke (e.g. ipsilateral carotid disease).
  • Greater than 3 Cerebral Micro-bleeds (CMB) on gradient recovery echo (GRE) or evidence of intracranial hemorrhage on CT at time of randomization. (SWI sequencing may be used if GRE sequencing is not obtainable)
  • Therapeutically anti-coagulated at time of admission (INR at admission greater than 2.0 on warfarin or took two consecutive doses of NOAC).
  • Absolute indication for use of warfarin only.( e.g. Mechanical Valve)
  • Absolute indication for anticoagulation prior to randomization window. (e.g. DVT)
  • Hemoglobin less than 9 gm/dl and/or platelet count less than 100 K/uL.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Bayfront Health St Petersburg

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33602, United States

Location

University of South Florida

Tampa, Florida, 33602, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Related Publications (3)

  • Alrohimi A, Rose DZ, Burgin WS, Renati S, Hilker NC, Deng W, Oliveira GH, Beckie TM, Labovitz AJ, Fradley MG, Tran N, Gioia LC, Kate M, Ng K, Dowlatshahi D, Field TS, Coutts SB, Siddiqui M, Hill MD, Miller J, Jickling G, Shuaib A, Buck B, Sharma M, Butcher KS. Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials. Int J Stroke. 2023 Aug;18(7):864-872. doi: 10.1177/17474930231164891. Epub 2023 Mar 26.

    PMID: 36907985DERIVED

  • Labovitz AJ, Rose DZ, Fradley MG, Meriwether JN, Renati S, Martin R, Kasprowicz T, Murtagh R, Kip K, Beckie TM, Stoddard M, Bozeman AC, McTigue T, Kirby B, Tran N, Burgin WS; AREST Investigators. Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial. Stroke. 2021 Apr;52(4):1164-1171. doi: 10.1161/STROKEAHA.120.030042. Epub 2021 Feb 25.

    PMID: 33626904DERIVED

  • Rose DZ, Meriwether JN, Fradley MG, Renati S, Martin RC, Kasprowicz T, Patel A, Mokin M, Murtagh R, Kip K, Bozeman AC, McTigue T, Hilker N, Kirby B, Wick N, Tran N, Burgin WS, Labovitz AJ. Protocol for AREST: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation-A Randomized Controlled Trial of Early Anticoagulation After Acute Ischemic Stroke in Atrial Fibrillation. Front Neurol. 2019 Sep 20;10:975. doi: 10.3389/fneur.2019.00975. eCollection 2019.

    PMID: 31620067DERIVED

MeSH Terms

Conditions

Ischemic Attack, TransientStrokeAtrial Fibrillation

Interventions

apixabanWarfarin

Condition Hierarchy (Ancestors)

Brain IschemiaCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesArrhythmias, CardiacHeart DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-HydroxycoumarinsCoumarinsBenzopyransPyransHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Results Point of Contact

Title
David Rose, MD
Organization
University of South Florida
drose1@usf.edu
813-259-8577

Study Officials

  • Michael Fradley, M.D.

    University of South Florida, Department of Cardiovascular Sciences

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 29, 2014

First Posted

November 5, 2014

Study Start

April 1, 2015

Primary Completion

June 1, 2019

Study Completion

June 1, 2019

Last Updated

November 30, 2021

Results First Posted

November 30, 2021

Record last verified: 2018-12

Locations

US(5)