Assessment of an Education and Guidance Programme for Eliquis Adherence in Non-Valvular Atrial Fibrillation (AEGEAN) (AEGEAN)

The study purpose is to assess the impact of an educational program on patient adherence in patients taking Apixaban for SPAF at 24 weeks

Study Overview

• Status: Completed
• Conditions: Non-valvular Atrial Fibrillation
• Intervention / Treatment: Drug: Apixaban

Detailed Description

SPAF=Stroke Prevention in Atrial Fibrillation

ISTH=International Society on Thrombosis and Hemostasis

Primary Purpose: Other: To measure adherence to the study medication using an electronic monitoring device over the first 24 weeks on study medication

• Study Type: Interventional
• Enrollment (Actual): 1217
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • Local Institution
  • Arlon, Belgium, 6700
    • Local Institution
  • Bonheiden, Belgium, 2820
    • Local Institution
  • Braine-l'alleud, Belgium, 1420
    • Local Institution
  • Brussels, Belgium, 1090
    • Local Institution
  • Bruxelles, Belgium, 1020
    • Local Institution
  • Gent, Belgium, 9000
    • Local Institution
  • Gilly, Belgium, 6060
    • Local Institution
  • Hasselt, Belgium, 3500
    • Local Institution
  • Leuven, Belgium, 3000
    • Local Institution
  • Liege, Belgium, 4000
    • Local Institution
  • Ronse, Belgium, 9600
    • Local Institution
  • Woluwe- Saint Lambert, Belgium, 1200
    • Local Institution
  • Yvoir, Belgium, 5530
    • Local Institution
  • Yvoir, Belgium, B-5530
    • Local Institution
• France
  • Abbeville, France, 80142
    • Local Institution
  • Aix En Provence, France, 13616
    • Local Institution
  • Avignon, France, 84000
    • Local Institution
  • Avignon Cedex 9, France, 84902
    • Local Institution
  • Bayonne, France, 64100
    • Local Institution
  • Bayonne Cedex, France, 64109
    • Local Institution
  • Beziers Cedex, France, 34525
    • Local Institution
  • Bobigny, France, 93009
    • Local Institution
  • Bordeaux, France, 33075
    • Local Institution
  • Bordeaux, France, 33000
    • Local Institution
  • Boulogne-billancourt, France, 92100
    • Local Institution
  • Brest, France, 29609
    • Local Institution
  • Bron, France, 69677
    • Local Institution
  • Caen, France, 14000
    • Local Institution
  • Cambrai, France, 59407
    • Local Institution
  • Cannes, France, 06400
    • Local Institution
  • Chambray-les- Tours, France, 37044
    • Local Institution
  • Chartes, France, 28108
    • Local Institution
  • Chatellerault, France, 86106
    • Local Institution
  • Cholet, France, 49309
    • Local Institution
  • Clermont Ferrand, France, 63003
    • Local Institution
  • Colombes, France, 92701
    • Local Institution
  • Corbeil Essonnes, France, 91106
    • Local Institution
  • Creteil Cedex, France, 94010
    • Local Institution
  • Dijon Cedex, France, 21079
    • Local Institution
  • Grenoble Cedex 09, France, 38043
    • Local Institution
  • Grenoble Cedex 9, France, 38043
    • Local Institution
  • Haguenau Cedex, France, 67502
    • Local Institution
  • La Rochelle Cedex, France, 17019
    • Local Institution
  • Le Chesnay, France, 78150
    • Local Institution
  • Lille, France, 59000
    • Local Institution
  • Lille Cedex, France, 59037
    • Local Institution
  • Longjumeau, France, 91164
    • Local Institution
  • Marseille, France, 13003
    • Local Institution
  • Marseille, France, 13385
    • Local Institution
  • Marseille, France, 13008
    • Local Institution
  • Marseille Cedex 20, France, 13915
    • Local Institution
  • Montfermeil, France, 93370
    • Local Institution
  • Montpellier, France, 34295
    • Local Institution
  • Montpellier, France, 34000
    • Local Institution
  • Nantes Cedex 2, France, 44277
    • Local Institution
  • Neuilly Sur Seine, France, 92523
    • Local Institution
  • Nice, France, 06105
    • Local Institution
  • Nimes Cedex 9, France, 30029
    • Local Institution
  • Orleans Cedex 2, France, 45067
    • Local Institution
  • Paris, France, 75013
    • Local Institution
  • Paris, France, 75010
    • Local Institution
  • Paris, France, 75908
    • Local Institution
  • Paris, France, 75015
    • Local Institution
  • Paris Cedex, France, 75013
    • Local Institution
  • Paris Cedex 14, France, 75674
    • Local Institution
  • Pau Universite Cedex, France, 64046
    • Local Institution
  • Pessac, France, 33604
    • Local Institution
  • Plan de Cuques, France, 13380
    • Local Institution
  • Rennes Cedex 9, France, 35033
    • Local Institution
  • Saint Denis, France, 93207
    • Local Institution
  • Salouel, France, 80480
    • Local Institution
  • Sete, France, 34200
    • Local Institution
  • St. Benoit, France, 86280
    • Local Institution
  • Strasbourg, France, 67090
    • Local Institution
  • Strasbourg, France, 67000
    • Local Institution
  • Thionville, France, 57100
    • Local Institution
  • Thonon Les Bains, France, 74203
    • Local Institution
  • Toulouse, France, 31054
    • Local Institution
  • Toulouse Cedex 3, France, 31076
    • Local Institution
  • Tourcoing, France, 59208
    • Local Institution
  • Valence, France, 26000
    • Local Institution
  • Valenciennes Cedex, France, 59322
    • Local Institution
  • Vesoul, France, 70014
    • Local Institution
  • Wardenburg, France, 26203
    • Local Institution
  • Cedex 2
    • Saint Etienne, Cedex 2, France, 42055
      • Local Institution
• Germany
  • Augsburg, Germany, 86159
    • Local Institution
  • Aurich, Germany, 26603
    • Local Institution
  • Bad Homburg, Germany, 61348
    • Local Institution
  • Balingen, Germany, 72336
    • Local Institution
  • Bamberg, Germany
    • Local Institution
  • Berin, Germany, 10559
    • Local Institution
  • Berlin, Germany, 12351
    • Local Institution
  • Berlin, Germany, 10367
    • Local Institution
  • Berlin, Germany, 10789
    • Local Institution
  • Berlin, Germany, 12524
    • Local Institution
  • Berlin, Germany, 13405
    • Local Institution
  • Chemnitz, Germany, 09122
    • Local Institution
  • Deggingen, Germany, 73326
    • Local Institution
  • Dillingen, Germany, 66763
    • Local Institution
  • Dresden, Germany, 01277
    • Local Institution
  • Dresden, Germany, 01099
    • Local Institution
  • Erfurt, Germany, 99084
    • Local Institution
  • Essen, Germany, 45138
    • Local Institution
  • Floersheim, Germany, 65439
    • Local Institution
  • Friedberg, Germany
    • Local Institution
  • Gars/Inn, Germany, 83536
    • Local Institution
  • Gottingen, Germany, 37073
    • Local Institution
  • Grossheirath Rossbach, Germany, 96269
    • Local Institution
  • Hamburg, Germany, 22299
    • Local Institution
  • Hamburg, Germany, 22459
    • Local Institution
  • Hassloch, Germany, 67454
    • Local Institution
  • Heidelberg, Germany, 69115
    • Local Institution
  • Heidenau, Germany, 01809
    • Local Institution
  • Kassel, Germany, 34117
    • Local Institution
  • Kelkheim, Germany, 65779
    • Local Institution
  • Kuenzing, Germany, 94550
    • Local Institution
  • Langestrasse, Germany, 04910
    • Local Institution
  • Leipzig, Germany, 04104
    • Local Institution
  • Lollar, Germany, 35457
    • Local Institution
  • Ludwigsburg, Germany, 71634
    • Local Institution
  • Ludwigsburg, Germany, 71640
    • Local Institution
  • Mammendorf, Germany, 82291
    • Local Institution
  • Mannheim, Germany, 68161
    • Local Institution
  • Mannheim, Germany, 68163
    • Local Institution
  • Markkleeberg, Germany, 04416
    • Local Institution
  • Munster, Germany, 48149
    • Local Institution
  • Myen, Germany, 56727
    • Local Institution
  • Neukirchen, Germany, 66539
    • Local Institution
  • Neunirchen, Germany, 66540
    • Local Institution
  • Northeim, Germany, 37154
    • Local Institution
  • Obermichelbach, Germany
    • Local Institution
  • Papenburg, Germany, D-26871
    • Local Institution
  • Pirna, Germany, 01796
    • Local Institution
  • Riesa, Germany, D-01587
    • Local Institution
  • Rodgau, Germany, 63110
    • Local Institution
  • Rotenburg /fulda, Germany, 36199
    • Local Institution
  • Sinzheim, Germany, 76547
    • Local Institution
  • Stockach, Germany, 78333
    • Local Institution
  • Unterschneidheim, Germany, 73485
    • Local Institution
  • Wallerfing, Germany, 94574
    • Local Institution
  • Wangen, Germany, 88239
    • Local Institution
  • Weissenhorn, Germany, 89264
    • Local Institution
  • Wermsdorf, Germany, 04779
    • Local Institution
  • Wetzlar, Germany, 35584
    • Local Institution
  • Weyhe, Germany, 28844
    • Local Institution
  • Winsen, Germany, 21423
    • Local Institution
  • Baden-wurttembe
    • Spaichingen, Baden-wurttembe, Germany, 78549
      • Local Institution
  • Bayern
    • Krombach, Bayern, Germany, 63829
      • Local Institution
• Italy
  • Arezzo, Italy, 52100
    • Local Institution
  • Bologna, Italy, 40133
    • Local Institution
  • Castelfranco Veneto (tv), Italy, 31033
    • Local Institution
  • Catanzaro, Italy, 88100
    • Local Institution
  • Cremona, Italy, 26100
    • Local Institution
  • Firenze, Italy, 50134
    • Local Institution
  • Firenze, Italy, 50122
    • Local Institution
  • Florence, Italy, 50134
    • Local Institution
  • Foggia, Italy, 71100
    • Local Institution
  • L'Aquila, Italy, 67100
    • Local Institution
  • Mestre, Italy, 30174
    • Local Institution
  • Milano, Italy, 20142
    • Local Institution
  • Milano, Italy, 20132
    • Local Institution
  • Naples, Italy, 80123
    • Local Institution
  • Napoli, Italy, 80131
    • Local Institution
  • Palermo, Italy, 90127
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
  • Perugia, Italy, 06132
    • Local Institution
  • Piacenza, Italy, 29100
    • Local Institution
  • Reggio Emilia, Italy, 42100
    • Local Institution
  • Roma, Italy, 00161
    • Local Institution
  • Roma, Italy, 00128
    • Local Institution
  • Roma, Italy, 00135
    • Local Institution
  • San Daniele Del Friuli(udine), Italy, 33038
    • Local Institution
  • Siena, Italy, 53100
    • Local Institution
  • Torino, Italy, 10126
    • Local Institution
  • Treviso, Italy, 31100
    • Local Institution
  • Varese, Italy, 21100
    • Local Institution
  • Vicenza, Italy, 36100
    • Local Institution
  • Vimercate, Italy, 20059
    • Local Institution
  • Viterbo, Italy, 01100
    • Local Institution
  • MI
    • Milano, MI, Italy, 20122
      • Local Institution
• Spain
  • Aldaya, Spain, 46960
    • Local Institution
  • Alicante, Spain, 03015
    • Local Institution
  • Barcelona, Spain, 08036
    • Local Institution
  • Barcelona, Spain, 08025
    • Local Institution
  • Barcelona, Spain, 08013
    • Local Institution
  • Galdacano, Spain, 48960
    • Local Institution
  • Madrid, Spain, 28033
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Madrid, Spain, 28009
    • Local Institution
  • Murcia, Spain, 30120 El Palmar
    • Local Institution
  • Oviedo, Spain, 33006
    • Local Institution
  • Santiago De Compostela, Spain, 15706
    • Local Institution
  • Tarragona, Spain, 43007
    • Local Institution
  • Valencia, Spain, 46026
    • Local Institution
  • Valencia, Spain, 46010
    • Local Institution
  • Viladecans, Spain, 08840
    • Local Institution
  • Zaragoza, Spain, 50009
    • Local Institution
  • Madrid
    • San Sebastian De Los Reyes, Madrid, Spain, 28702
      • Local Institution
• Switzerland
  • Baden, Switzerland, 5404
    • Local Institution
  • Bern 4, Switzerland, 3004
    • Local Institution
  • Winterthur, Switzerland, 8401
    • Local Institution
  • Zurich, Switzerland, 8032
    • Local Institution
  • Zurich, Switzerland, 8063
    • Local Institution
  • Canton
    • Fribourg, Canton, Switzerland, 1708
      • Local Institution
  • Ticino
    • Lugano, Ticino, Switzerland, 6900
      • Local Institution
• United Kingdom
  • Hereford, United Kingdom, HR12ER
    • Local Institution
  • Oldham, United Kingdom, OL12JH
    • Local Institution
  • Somerset, United Kingdom, BA21 4AT
    • Local Institution
  • Tauton, United Kingdom, TA1 5DA
    • Local Institution
  • Armagh
    • Craigavon, Armagh, United Kingdom, BT63 5QQ
      • Local Institution
  • County Durham
    • Darlington, County Durham, United Kingdom, DL3 8SQ
      • Local Institution
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Local Institution
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • Local Institution
    • Poole, Dorset, United Kingdom, BH15 2JB
      • Local Institution
  • Essex
    • Westcliff-on-sea, Essex, United Kingdom, SS0 0RT
      • Local Institution
  • Kent
    • Ashford, Kent, United Kingdom, TN24 0LZ
      • Local Institution
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G75 8RG
      • Local Institution
  • Lancashire
    • Airdrie, Lancashire, United Kingdom, ML6 OJS
      • Local Institution
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Local Institution
  • Staffordshire
    • Stoke-on-trent, Staffordshire, United Kingdom, ST4 6QG
      • Local Institution
  • WEST Midlands
    • Birmingham, WEST Midlands, United Kingdom, B18 7QH
      • Local Institution
    • Dudley, WEST Midlands, United Kingdom, DY1 2HQ
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with diagnosed non-valvular Atrial Fibrillation (AF) or atrial flutter (documented by 12-lead electrocardiogram (ECG) or Holter recording) and eligible for oral anticoagulant (OAC) therapy

2. Presence of at least one of the following risk factors for stroke:

   Prior stroke or transient ischaemic attack (TIA)

   • Age ≥75 years
   • Hypertension
   • Diabetes mellitus
   • Symptomatic heart failure [New York Heart Association (NYHA) Class ≥II]
3. Must be able to self-administer treatment
4. Either Vitamin K antagonists (VKA) treated or VKA naive. Patients treated with VKA should have received the VKA treatment for ≥3 months. VKA naïve patients should not have received VKA treatment for more than 30 days within the last 12 months. Patients who are not described by either of the above criteria are not eligible for the study
5. Patients previously treated with acetylsalicylic acid (ASA) for stroke prevention are allowed (and will switch to Apixaban)
6. Patients with screening mini-mental state examination (MMSE) more than 24
7. Subject Re-enrollment: This study does not permit the re-enrollment of a subject that has discontinued the study as a pre-treatment failure

Age and Reproductive Status:

• i) Men and women ≥18 years of age
• ii) Women of childbearing potential (WOCBP) must use method(s) of contraception based on the tables in protocol. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study medication
• iv) Women must not be breastfeeding
• v) Men who are sexually active with women of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year
• vi) Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile); and azoospermic men do not require contraception

Exclusion Criteria:

1. Target Disease Exceptions:

   1. Atrial fibrillation or flutter due to reversible causes (e.g. thyrotoxicosis, pericarditis)
   2. Clinically significant (moderate or severe) mitral stenosis
   3. Cardiac valvular disease requiring surgery
   4. Planned major surgery or/and invasive procedure and/or atrial fibrillation or flutter, ablation procedure and/or cardioversion
   5. Patients receiving Rivaroxaban, Dabigatran or Apixaban

2. Medical History and Concurrent Diseases:

   1. Conditions other than atrial fibrillation that require chronic anticoagulation (e.g., prosthetic mechanical heart valve, venous thromboembolism; also see Section 3.4, Concomitant Treatments)

   2. Patient with serious bleeding in the last 6 months or with a lesion or condition at high risk of bleeding such as:

      • Active peptic ulcer disease, current or recent gastrointestinal ulceration
      • Known or suspected esophageal varices
      • Recent ischemic stroke (within 7 days)
      • Recent brain or spinal injury or intracranial hemorrhage
      • Recent brain, spinal or ophthalmic surgery
      • Arteriovenous malformations
      • Vascular aneurysms
      • Major intraspinal or intracerebral vascular abnormalities
      • Documented hemorrhagic tendencies or blood dyscrasias
      • Presence of malignant neoplasms at high risk of bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1: Apixaban (Primary SOC information); Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and Primary Standard of Care (SOC) information	Drug: Apixaban; Other Names: Eliquis; BMS-562247
EXPERIMENTAL: Arm 2: Apixaban (Additional Educational Program); Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and Additional Educational Program	Drug: Apixaban; Other Names: Eliquis; BMS-562247

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen	The mean percentage of days which participants maintained adherence to apixaban treatment was measured for each arm. Adherence to apixaban = number of units of adherence *100 / total number of eligible days for the time period from first dose date, up to 169 days. Unit of adherence: A 24-hour window where the treatment is taken as prescribed, ie, 1 tablet (5 mg or 2.5 mg, as appropriate) 2 times a day. If only one dose is missed in 24-hours, it is still considered as a unit of adherence. Adherence up to 24 weeks was calculated as the percentage of adherence units within that period. If a participant discontinued from the study before 24 weeks, the denominator time period was censored at the earlier of last dose date or discontinuation date for discontinuation due to reasons unrelated to participant adherence, such as withdrawn consent, or AE; otherwise, the period was censored at the minimum of 169 days and last dose date + 30 days.	Day 1 up to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 12 to 24 Weeks Period Compared With During the First 12 Weeks	The mean adherence to apixaban treatment during the first 24 weeks was measured between the standard of care (SOC) information and Additional Education Program (AEP) arms and expressed as a percentage. Adherence to Apixaban = number of units of adherence *100 / total number of eligible days for the time period.	Day 1 to Week 12, Week 12 to Week 24
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 24 to 48 Weeks Period	The mean percentage of days which participants maintained adherence to apixaban treatment was measured for each arm. Adherence to apixaban = number of units of adherence *100 / total number of eligible days for the time period from first dose date, up to 169 days. Unit of adherence: A 24-hour window where the treatment is taken as prescribed, ie, 1 tablet (5 mg or 2.5 mg, as appropriate) 2 times a day. If only one dose is missed in 24-hours, it is still considered as a unit of adherence. Adherence over 24 weeks was calculated as the percentage of adherence units within that period. If a participant discontinued from the study before 48 weeks, the denominator time period was censored at the earlier of last dose date or discontinuation date for discontinuation due to reasons unrelated to participant adherence, such as withdrawn consent, or AE; otherwise, the period was censored at the minimum of 169 days and last dose date + 30 days.	Week 24 to Week 48
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks	Logit analyses were conducted on the Primary Efficacy Set to identify non-adherence predictors of 20% or more (vs. at least 80% adherence) at 24 weeks. In the Primary SOC group, alcohol use, Mini-Mental State Evaluation (MMSE) score, UK standard occupational classification, and type of atrial fibrillation were retained in the model (p-value <= 0.2). In the Additional Educational Program group, alcohol use, type of atrial fibrillation, age and Vitamin K Antagonists (VKA) status were retained in the model (p-value <= 0.2). Odds ratios are presented for predictors of non-adherence.	Week 24
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death	AEs with onset date from day 1 through week 24 are included in this summary. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.	Day 1 up to week 24
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death	Adverse events with onset date after 24 weeks are included in this summary. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.	Week 24 up to Week 48

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Montalescot G, Brotons C, Cosyns B, Crijns HJ, D'Angelo A, Drouet L, Eberli F, Lane DA, Besse B, Chan A, Vicaut E, Darius H; AEGEAN Study Investigators. Educational Impact on Apixaban Adherence in Atrial Fibrillation (the AEGEAN STUDY): A Randomized Clinical Trial. Am J Cardiovasc Drugs. 2020 Feb;20(1):61-71. doi: 10.1007/s40256-019-00356-2.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2013
• Primary Completion (ACTUAL): January 20, 2016
• Study Completion (ACTUAL): January 20, 2016

Study Registration Dates

• First Submitted: June 13, 2013
• First Submitted That Met QC Criteria: June 20, 2013
• First Posted (ESTIMATE): June 24, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 19, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: CV185-220; 2013-000055-41 (EUDRACT_NUMBER)