Non-valvular Atrial Fibrillation
Conditions
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
Interventions
DRUGApixaban
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen | Day 1 up to week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 1 to Week 12, Week 12 to Week 24 | 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. |
| Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 24 to 48 Weeks Period | Week 24 to Week 48 | 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. |
| Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Week 24 | 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. |
| Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Day 1 up to week 24 | 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. |
Countries
Belgium, France, Germany, Italy, Spain, Switzerland, United Kingdom
Participant flow
Pre-assignment details
1217 participants were enrolled, 1162 randomized (583 Primary SOC,579 AEP). 55 were enrolled but not randomized. Of the 55, 13 no longer met study criteria, 13 withdrew consent, 3 lost to follow-up, 10 other and 16 unknown.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban (Primary SOC Information) Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information. | 583 |
| Apixaban (Additional Educational Program) Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group. | 579 |
| Total | 1,162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Primary Efficacy Analysis Set (24 Weeks) | Adverse Event | 15 | 11 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Death | 6 | 4 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Drug Interruption >30 Consecutive Days | 0 | 2 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Helping Hand not used | 2 | 0 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Helping Hand not used, treatment taken | 1 | 1 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Inclusion/exclusion criterion | 2 | 5 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Lost to Follow-up | 0 | 1 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Medical reason | 3 | 3 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Serious Adverse Event | 7 | 6 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Subject Withdrew Consent | 17 | 20 | 0 |
| Primary Efficacy Analysis Set (24 Weeks) | Withdrawal by Subject | 1 | 1 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Adverse Event | 17 | 3 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Death | 7 | 3 | 3 |
| Primary Efficacy Analysis Set (48 Weeks) | Drug Interruption >30 Consecutive Days | 3 | 0 | 2 |
| Primary Efficacy Analysis Set (48 Weeks) | Helping Hand not used | 4 | 0 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Helping Hand not used, treatment taken | 3 | 0 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Inclusion / Exclusion Criterion | 2 | 0 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Lost to Follow-up | 1 | 0 | 1 |
| Primary Efficacy Analysis Set (48 Weeks) | Medical reason | 4 | 1 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Serious Adverse Event | 17 | 6 | 3 |
| Primary Efficacy Analysis Set (48 Weeks) | Subject decision | 1 | 0 | 0 |
| Primary Efficacy Analysis Set (48 Weeks) | Subject Withdrew Consent | 21 | 0 | 2 |
Baseline characteristics
| Characteristic | Apixaban (Primary SOC Information) | Apixaban (Additional Educational Program) | Total |
|---|---|---|---|
| Age, Continuous | 72.6 years STANDARD_DEVIATION 8.94 | 73.1 years STANDARD_DEVIATION 9.05 | 72.9 years STANDARD_DEVIATION 9 |
| Age, Customized 64-74 years | 221 Participants | 220 Participants | 441 Participants |
| Age, Customized <64 years | 86 Participants | 77 Participants | 163 Participants |
| Age, Customized >=75 years | 276 Participants | 282 Participants | 558 Participants |
| Sex: Female, Male Female | 232 Participants | 234 Participants | 466 Participants |
| Sex: Female, Male Male | 351 Participants | 345 Participants | 696 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 604 | 5 / 308 | 5 / 223 | 46 / 558 | 21 / 604 |
| serious Total, serious adverse events | 69 / 604 | 40 / 308 | 29 / 223 | 79 / 558 | 62 / 604 |
Outcome results
Primary
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.
Time frame: Day 1 up to week 24
Population: Primary efficacy analysis set (Week 24), which consists of all randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apixaban (Primary SOC Information) | Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen | 91.64 percentage of days | Standard Deviation 17.143 |
| Apixaban (Additional Educational Program) | Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen | 91.88 percentage of days | Standard Deviation 16.14 |
p-value: 0.811795% CI: [-2.18, 1.7]t-test, 2 sided
Secondary
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.
Time frame: Week 24
Population: Primary Efficacy Set participants with evaluable data at week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Higher professional occupations vs UKSOC1 | 0.898 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Lower supervisory and tech. occupations vs UKSOC1 | 3.587 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | >=3 Alcoholic Drink/Day Average vs None | 4.268 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Never worked and long-term unemployed vs UKSOC1 | 1.289 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Intermediate occupations vs UKSOC1 | 1.230 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Routine occupations vs UKSOC1 | 0.508 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Higher mgmt., adm. and professional jobs vs UKSOC1 | 0.827 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Semi-routine occupations vs UKSOC1 | 0.450 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Large employers and mgmt. and adm. jobs vs UKSOC1 | 2.823 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Paroxysmal vs Persistant Atrial Fibrillation | 1.626 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Mini-mental state examination score | 0.808 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Permanent vs Persistant Atrial Fibrillation | 2.560 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Lower mgmt., adm. and professional jobs vs UKSOC1 | 0.948 Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | VKA Naïve vs Non-Naïve | NA Odds ratio |
| Apixaban (Primary SOC Information) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | <=2 Alcoholic Drink/Day Average vs None | 1.251 Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | VKA Naïve vs Non-Naïve | 1.686 Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | <=2 Alcoholic Drink/Day Average vs None | 0.994 Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | >=3 Alcoholic Drink/Day Average vs None | 3.782 Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Mini-mental state examination score | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Higher mgmt., adm. and professional jobs vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Higher professional occupations vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Intermediate occupations vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Large employers and mgmt. and adm. jobs vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Lower mgmt., adm. and professional jobs vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Lower supervisory and tech. occupations vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Never worked and long-term unemployed vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Routine occupations vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Semi-routine occupations vs UKSOC1 | NA Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Paroxysmal vs Persistant Atrial Fibrillation | 1.911 Odds ratio |
| Apixaban (Additional Educational Program) | Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks | Permanent vs Persistant Atrial Fibrillation | 1.846 Odds ratio |
p-value: 0.1924Wald Chi-square test
p-value: 0.0305Wald Chi-square test
p-value: 0.0107Wald Chi-square test
p-value: 0.6982Wald Chi-square test
p-value: 0.7277Wald Chi-square test
p-value: 0.7581Wald Chi-square test
p-value: 0.2328Wald Chi-square test
p-value: 0.7507Wald Chi-square test
p-value: 0.0091Wald Chi-square test
p-value: 0.673Wald Chi-square test
p-value: 0.0117Wald Chi-square test
p-value: 0.191Wald Chi-square test
p-value: 0.9559Wald Chi-square test
p-value: 0.0264Wald Chi-square test
p-value: 0.1087Wald Chi-square test
p-value: 0.0679Wald Chi-square test
p-value: 0.2128Wald Chi-square test
p-value: 0.3739Wald Chi-square test
p-value: 0.843Wald Chi-square test
Secondary
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.
Time frame: Day 1 up to week 24
Population: All randomized participants. Participants in the safety analysis set were categorized according to the counseling actually received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | SAE | 75 Participants |
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Drug related AE | 54 Participants |
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | AE leading to discontinuation | 33 Participants |
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Death | 6 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Death | 5 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | SAE | 82 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | AE leading to discontinuation | 22 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Drug related AE | 41 Participants |
Secondary
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.
Time frame: Week 24 up to Week 48
Population: All randomized participants remaining in the study after week 24. All randomized participants. Participants in the safety analysis set were categorized according to the counseling actually received
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | SAE | 71 Participants |
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Drug related AE | 15 Participants |
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | AE leading to discontinuation | 14 Participants |
| Apixaban (Primary SOC Information) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Death | 3 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Death | 3 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | SAE | 43 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | AE leading to discontinuation | 3 Participants |
| Apixaban (Additional Educational Program) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Drug related AE | 12 Participants |
| Apixaban (Secondary SOC) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Death | 6 Participants |
| Apixaban (Secondary SOC) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | Drug related AE | 10 Participants |
| Apixaban (Secondary SOC) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | AE leading to discontinuation | 8 Participants |
| Apixaban (Secondary SOC) | Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death | SAE | 30 Participants |
Secondary
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.
Time frame: Day 1 to Week 12, Week 12 to Week 24
Population: Primary efficacy analysis set (Week 24) with available data at both study days 85 and 169
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apixaban (Primary SOC Information) | 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 | Day 1 to Week 12 | 93.7 percentage | Standard Deviation 14.18 |
| Apixaban (Primary SOC Information) | 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 | Week 12 to Week 24 | 90.3 percentage | Standard Deviation 20.64 |
| Apixaban (Additional Educational Program) | 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 | Day 1 to Week 12 | 93.0 percentage | Standard Deviation 15.71 |
| Apixaban (Additional Educational Program) | 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 | Week 12 to Week 24 | 90.9 percentage | Standard Deviation 18.36 |
Comparison: Percent adherence at 12 Weeks v. Percent adherence at 24 Weeksp-value: <0.0001paired t-test
Comparison: Percent adherence at 12 Weeks v. Percent adherence at 24 Weeksp-value: <0.0001paired t-test
Secondary
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.
Time frame: Week 24 to Week 48
Population: All treated participants in 24 to 48-week period. Participants that had not been using the EMD consistently throughout the study were excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apixaban (Primary SOC Information) | Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 24 to 48 Weeks Period | 87.59 percentage | Standard Deviation 22.921 |
| Apixaban (Additional Educational Program) | Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 24 to 48 Weeks Period | 88.41 percentage | Standard Deviation 22.148 |
| Apixaban (Secondary SOC) | Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 24 to 48 Weeks Period | 87.51 percentage | Standard Deviation 21.125 |
p-value: 0.8707ANOVA
p-value: 0.639995% CI: [-2.88, 4.68]t-test, 2 sided
p-value: 0.961695% CI: [-3.45, 3.29]t-test, 2 sided
p-value: 0.634195% CI: [-2.6, 4.24]t-test, 2 sided