Early Administration of Edoxaban After Acute Ischemic Stroke in Patients With Non-valvular Atrial Fibrillation
NCT ID: NCT03433235
Last Updated: 2020-12-11
Study Results
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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COMPLETED
PHASE2
68 participants
INTERVENTIONAL
2018-06-19
2020-07-02
Brief Summary
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Detailed Description
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For this reason, urgent anticoagulation has not been recommended in stroke patients with AF, and the appropriate time point to start anticoagulation remains controversial. Guideline recommends 1-3-6-12 rule\* in initiating anticoagulation. However, this rule is not derived from a scientifically proven study results. Furthermore, although the risk of intracranial hemorrhage may be reduced to some extent with this strategy, the risk of early recurrence of embolic stroke may outweigh the potential benefit of delayed anticoagulation.
Edoxaban, which selectively blocks factor Xa, has a lower risk of hemorrhage, but with a similar efficacy in preventing ischemic events in patients with AF compared with warfarin. Even compared with the other factor Xa inhibitors, it is considered to have a lower risk of bleeding. Therefore, edoxaban may be safely given in the early phase in patients with stroke associated with AF, while not significantly increasing the risk of hemorrhages.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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Early edoxaban initiation group
Low dose of edoxaban (15 or 30 mg) once daily from Day 2, then standard dose of edoxaban (30 or 60 mg) according to '3-6' rule.
Edoxaban
1-3-6-12 rule\*
Anticoagulation in patients with acute ischemic stroke and atrial fibrillation can be initiated from the following days after stroke event.
After 1 day: transient ischemic attacks
After 3 days: mild ischemic strokes (NIHSS \<8)
After 6 days: moderate ischemic strokes (NIHSS 8-16)
After 12 days: severe ischemic strokes (NIHSS \>16)
\- NIHSS: National Institute of Health Stroke Scales
Conventional edoxaban initiation group
No antithrombotic treatment† -- then standard dose of edoxaban (30 or 60 mg) according to '3-6' rule.
Edoxaban
1-3-6-12 rule\*
Anticoagulation in patients with acute ischemic stroke and atrial fibrillation can be initiated from the following days after stroke event.
After 1 day: transient ischemic attacks
After 3 days: mild ischemic strokes (NIHSS \<8)
After 6 days: moderate ischemic strokes (NIHSS 8-16)
After 12 days: severe ischemic strokes (NIHSS \>16)
\- NIHSS: National Institute of Health Stroke Scales
Interventions
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Edoxaban
1-3-6-12 rule\*
Anticoagulation in patients with acute ischemic stroke and atrial fibrillation can be initiated from the following days after stroke event.
After 1 day: transient ischemic attacks
After 3 days: mild ischemic strokes (NIHSS \<8)
After 6 days: moderate ischemic strokes (NIHSS 8-16)
After 12 days: severe ischemic strokes (NIHSS \>16)
\- NIHSS: National Institute of Health Stroke Scales
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Evidence of persistent or paroxysmal atrial fibrillation (already known or newly detected)
3. Age ≥20 y
4. Patients who provided informed consent
Exclusion Criteria
2. Significant hemorrhagic transformation (parenchymal hematoma type I or type II by the ECASS definition or those accompanying with worsening of an existing focal neurological deficit \[NIHSS ≥4\])10 on baseline MRI
3. Mechanical heart valve, rheumatic heart valve disease, or any other conditions requiring strong anticoagulation such as vitamin K antagonist or heparin treatment
4. Concomitant significant atherosclerotic stenosis (\>50%) in the proximal arteries, which are possibly responsible for stroke lesions
5. Recent (\<3 months) history of cerebral bleeding
6. Active internal bleeding or clinically significant bleeding
7. Severe anemia (Hb \<10 g/dL) or bleeding diathesis (platelet count \<100,000/uL or PT-INR \>1.7) (If there is no active bleeding sign, it is permitted to enroll Hb \<9 g/dL , platelet count \<70,000/uL)
8. Uncontrolled hypertension: persistent systolic pressure \>180 mmHg or diastolic pressure \>110 mmHg
9. Active, advanced medical diseases (liver, kidney, pulmonary disease or cancer) with a life expectancy \<6 months
10. Renal impairment (CrCl \<30 mL/min) or undergoing Hemodialysis (or Peritoneal Dialysis)
11. Treatment with a strong inducer of p-glycoprotein (carbamazepine, dexamethasone, doxorubicin, nefazodone, pentobarbital, phenobarbital, prazocin, rifampin, St.John's wort, tenofovir, tipranavir, trazodone, vinblastine)
12. Contraindication to MRI
13. Pregnancy, breast-feeding or having a plan to be pregnant
14. Participation in the other investigational drug trials simultaneously or within 3 months before the first administration of the study medication. Observational studies without an intervention (eg study medication) are allowed.
15. Any clinical conditions (eg abnormal lab tests) unsuitable for undergoing clinical trials at the discretion of the clinical investigators
16. Known hypersensitivity to the study drug (edoxaban), its ingredients, or formulation excipients
17. Patient with liver disease related to coagulation disorder and clinically significant bleeding risk
18. Severe Liver disease
19. Patient who has increase risk of bleeding due to the following disease
* recent gastrointestinal ulcer history
* carcinoma increased risk of bleeding
* recent brain or spinal injury
* recent brain, spinal or optical surgery histroy
* esophageal varix
* arteriovenous malformations
* vascular aneurysms (over 3.5cm)
* intra spinal or cerebral vascular disorder
20. Patient with other anticoagulants
21. intermitant or severe mitral stenosis
22. a pulmonary embolism patient who is hemodynamic unstabled or required thrombolytic therpy or pulmonary emnolectomy
20 Years
ALL
No
Sponsors
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Kyung Hee University Hospital
OTHER
Soon Chun Hyang University
OTHER
Dong-A University Hospital
OTHER
Jong Sung Kim
OTHER
Responsible Party
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Jong Sung Kim
Professor
Principal Investigators
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Jong Sung Kim, M.D.,Ph D.
Role: PRINCIPAL_INVESTIGATOR
Asan Medical Center
Locations
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Asan Medical Center
Seoul, , South Korea
Countries
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References
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Lin HJ, Wolf PA, Kelly-Hayes M, Beiser AS, Kase CS, Benjamin EJ, D'Agostino RB. Stroke severity in atrial fibrillation. The Framingham Study. Stroke. 1996 Oct;27(10):1760-4. doi: 10.1161/01.str.27.10.1760.
Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013 Mar;44(3):870-947. doi: 10.1161/STR.0b013e318284056a. Epub 2013 Jan 31.
Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J. 2013 Jul;34(27):2094-106. doi: 10.1093/eurheartj/eht134. Epub 2013 Apr 26.
Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P; ESC Scientific Document Group. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary. Eur Heart J. 2017 Jul 14;38(27):2137-2149. doi: 10.1093/eurheartj/ehw058.
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.
Schulman S. New oral anticoagulant agents - general features and outcomes in subsets of patients. Thromb Haemost. 2014 Apr 1;111(4):575-82. doi: 10.1160/TH13-09-0803. Epub 2014 Jan 23.
Kang DW, Han MK, Kim HJ, Sohn H, Kim BJ, Kwon SU, Kim JS, Warach S. Silent new ischemic lesions after index stroke and the risk of future clinical recurrent stroke. Neurology. 2016 Jan 19;86(3):277-85. doi: 10.1212/WNL.0000000000002289. Epub 2015 Dec 18.
Lee EJ, Kang DW, Warach S. Silent New Brain Lesions: Innocent Bystander or Guilty Party? J Stroke. 2016 Jan;18(1):38-49. doi: 10.5853/jos.2015.01410. Epub 2015 Oct 15.
Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 Oct 17;352(9136):1245-51. doi: 10.1016/s0140-6736(98)08020-9.
Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
Duchin K, Duggal A, Atiee GJ, Kidokoro M, Takatani T, Shipitofsky NL, He L, Zhang G, Kakkar T. An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in Healthy Adults. Clin Pharmacokinet. 2018 Feb;57(2):221-228. doi: 10.1007/s40262-017-0554-0.
Seiffge DJ, Traenka C, Polymeris A, Hert L, Peters N, Lyrer P, Engelter ST, Bonati LH, De Marchis GM. Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events. Neurology. 2016 Nov 1;87(18):1856-1862. doi: 10.1212/WNL.0000000000003283. Epub 2016 Sep 30.
Other Identifiers
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AMC 2018-0033
Identifier Type: -
Identifier Source: org_study_id