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Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation (AREST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02283294
Recruitment Status : Completed
First Posted : November 5, 2014
Results First Posted : November 30, 2021
Last Update Posted : November 30, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of South Florida

Tracking Information
First Submitted Date  ICMJE October 29, 2014
First Posted Date  ICMJE November 5, 2014
Results First Submitted Date  ICMJE July 7, 2021
Results First Posted Date  ICMJE November 30, 2021
Last Update Posted Date November 30, 2021
Actual Study Start Date  ICMJE April 2015
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2021)
Number of Participants With a Composite Endpoint of Fatal Stroke, Recurrent Ischemic Stroke, or TIA [ Time Frame: 180 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2014)
Composite endpoint of fatal stroke, recurrent ischemic stroke, or hemorrhagic stroke [ Time Frame: 180 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2021)
Number of Participants With an Intracranial Hemorrhage Assessed by MRI/CT [ Time Frame: 180 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2014)
  • Any intracranial bleeds assessed by MRI/CT scan at day 14 and EOS or at outcome event [ Time Frame: 180 days ]
  • Any major bleeds [ Time Frame: 180 days ]
    clinically overt bleeding that was accompanied by one or more of the following: a decrease in hemoglobin of 2 g/dL or more; a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least one of the following critical sites: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or bleeding that was fatal. Intracranial hemorrhage included intracerebral (hemorrhagic stroke), subarachnoid, and subdural bleeds.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation
Official Title  ICMJE Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation
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.
Detailed Description This is an Open label, randomized, active control, parallel-group pilot trial to examine the effect of initiation of APIXABAN at days 0-3 (TIA), days 3-5 (small stroke) and days 7-9 (medium stroke) to decrease fatal and/or recurrent stroke/TIA in 120 subjects who have suffered a recent( 0 to 48 hours from symptoms) TIA, or small to medium ischemic stroke compared to standard of care warfarin treatment regimen. Subjects will be randomly assigned in a 1:1 ratio to one of two treatment arms (apixaban or warfarin). Subjects will be followed for a total of 180 days during from screening through monthly follow-up visits.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Transient Ischemic Attack
  • Stroke
  • Atrial Fibrillation
Intervention  ICMJE
  • Drug: Apixaban
  • Drug: Warfarin
Study Arms  ICMJE
  • Experimental: Apixaban
    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
    Intervention: Drug: Apixaban
  • Active Comparator: Warfarin
    standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke).
    Intervention: Drug: Warfarin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2019)
91
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2014)
120
Actual Study Completion Date  ICMJE June 2019
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Signed Written Informed Consent
  2. Males and Females over 18 years of age.
  3. 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 .
  4. Diagnosis of TIA or small or medium ischemic stroke 0 to 48 hours from signs or symptoms.
  5. 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.
  6. 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.
  7. 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.
  8. 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
  • Vasectomy.
  • Complete Abstinence

Exclusion Criteria:

  1. Hemorrhagic stroke
  2. Large ischemic stroke
  3. History of major bleeding within the last 6 months from time of subject enrollment (e.g. GI bleed).
  4. History of intracranial bleed

    a. Traumatic intracranial bleed within one year of randomization. (Traumatic ICH greater than one year of randomization is not an exclusion).

  5. Current or history of bleeding disorders (e.g. blood dycrasias)
  6. Blood Pressure of 180/100 mmHg on hypertensive therapy day of randomization per PI discretion 20.
  7. Current illicit drug use and/or chronic alcohol use per PI discretion.
  8. Severe liver disease (AST/ALT 2x upper limit).
  9. 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) .
  10. Any other suspected etiology for stroke (e.g. ipsilateral carotid disease).
  11. 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)
  12. Therapeutically anti-coagulated at time of admission (INR at admission greater than 2.0 on warfarin or took two consecutive doses of NOAC).
  13. Absolute indication for use of warfarin only.( e.g. Mechanical Valve)
  14. Absolute indication for anticoagulation prior to randomization window. (e.g. DVT)
  15. Hemoglobin less than 9 gm/dl and/or platelet count less than 100 K/uL.
  16. Requires dual antiplatelet therapy.
  17. Daily use of NSAIDS
  18. Pregnancy or lactation.
  19. Any use of an investigational product within the past 30 days.
  20. Prisoners or subjects who are involuntarily incarcerated.
  21. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
  22. Concurrent participation in another clinical study where use of an investigational product is used
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02283294
Other Study ID Numbers  ICMJE PRO00019754
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of South Florida
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of South Florida
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Michael Fradley, M.D. University of South Florida, Department of Cardiovascular Sciences
PRS Account University of South Florida
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP