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

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

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

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

Conditions
-----------------
Non-valvular Atrial Fibrillation

Intervention / Treatment
-----------------
* Drug: Apixaban


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 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] Must be able to self-administer treatment 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 Patients previously treated with acetylsalicylic acid (ASA) for stroke prevention are allowed (and will switch to Apixaban) Patients with screening mini-mental state examination (MMSE) more than 24 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: Target Disease Exceptions: Atrial fibrillation or flutter due to reversible causes (e.g. thyrotoxicosis, pericarditis) Clinically significant (moderate or severe) mitral stenosis Cardiac valvular disease requiring surgery Planned major surgery or/and invasive procedure and/or atrial fibrillation or flutter, ablation procedure and/or cardioversion Patients receiving Rivaroxaban, Dabigatran or Apixaban Medical History and Concurrent Diseases: Conditions other than atrial fibrillation that require chronic anticoagulation (e.g., prosthetic mechanical heart valve, venous thromboembolism; also see Section 3.4, Concomitant Treatments) 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Apixaban (Primary SOC information)<br>Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and Primary Standard of Care (SOC) information | Drug: Apixaban<br> <br> * Other names: BMS-562247;|
| Experimental: Arm 2: Apixaban (Additional Educational Program)<br>Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and Additional Educational Program | Drug: Apixaban<br> <br> * Other names: 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 |