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

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ClinicalTrials.gov Identifier: NCT02283294
Recruitment Status : Recruiting
First Posted : November 5, 2014
Last Update Posted : July 23, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of South Florida

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.

Condition or disease Intervention/treatment Phase
Transient Ischemic Attack Stroke Atrial Fibrillation Drug: Apixaban Drug: Warfarin Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation
Study Start Date : April 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
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
Drug: Apixaban
Active Comparator: Warfarin
standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke).
Drug: Warfarin



Primary Outcome Measures :
  1. Composite endpoint of fatal stroke, recurrent ischemic stroke, or hemorrhagic stroke [ Time Frame: 180 days ]

Secondary Outcome Measures :
  1. Any intracranial bleeds assessed by MRI/CT scan at day 14 and EOS or at outcome event [ Time Frame: 180 days ]
  2. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283294


Contacts
Contact: Nhi Tran, MS 813-259-0628 nntran@health.usf.edu
Contact: Heather Glunk, RN 813-259-0671 hglunk@health.usf.edu

Locations
United States, California
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Jason Ledesma       jason.ledesma@labiomed.org   
Principal Investigator: Bijal Mehta, MD         
United States, Florida
Bayfront Health St Petersburg Recruiting
Saint Petersburg, Florida, United States, 33701
Contact: Kimberly Delmontagne, RN       kimberly.delmontagne@bayfronthealth.com   
Contact: Tina Henderson       tina.henderson@bayfronthealth.com   
Principal Investigator: Ravikiran Korabathina, MD         
Tampa General Hospital Recruiting
Tampa, Florida, United States, 33602
Contact: Anderson Brabson, MS, MHSA       c-rbrabson@tgh.org   
Principal Investigator: Arthur Labovitz, MD         
Sub-Investigator: W. Scott Burgin, MD         
Sub-Investigator: David Rose, MD         
Sub-Investigator: Swetha Renati, MD         
University of South Florida Recruiting
Tampa, Florida, United States, 33602
Contact: Nhi Tran, MS    813-259-0628    nntran@health.usf.edu   
Principal Investigator: Arthur Labovitz, MD         
Sub-Investigator: W. Scott Burgin, MD         
Sub-Investigator: David Rose, MD         
Sub-Investigator: Swetha Renati, MD         
Sub-Investigator: Michael Fradley, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Rita Longaker, RN    502-386-4134    rita.longaker@louisville.due   
Principal Investigator: Marcus Stoddard, MD         
Sponsors and Collaborators
University of South Florida
Bristol-Myers Squibb
Investigators
Principal Investigator: Arthur Labovitz, M.D. University of South Florida, Department of Cardiovascular Sciences

Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT02283294     History of Changes
Other Study ID Numbers: PRO00019754
First Posted: November 5, 2014    Key Record Dates
Last Update Posted: July 23, 2018
Last Verified: November 2017

Additional relevant MeSH terms:
Ischemic Attack, Transient
Stroke
Atrial Fibrillation
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Brain Ischemia
Apixaban
Warfarin
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action