E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with diagnosed non-valvular atrial fibrillation or atrial flutter
with at least one risk factor for stroke and indicated for oral
anticoagulant. |
|
E.1.1.1 | Medical condition in easily understood language |
Atrial fibrillation or rapid atrial rythm with risk of stroke. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the impact of educational programme on implementation phase adherence in patients taking apixaban for SPAF at 24 weeks. |
|
E.2.2 | Secondary objectives of the trial |
- To identify predictive risk factors linked to non-adherence in patients treated with apixaban.
- To compare implementation phase adherence to apixaban treatment with secondary SOC versus (1) primary SOC and (2) continued additional educational program.
- To compare implementation phase adherence to apixaban treatment at 12 weeks vs 24 weeks within groups.
- To evaluate impact of educational programme on safety profile of apixaban.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed Written Informed Consent.
- Patients with diagnosed non-valvular atrial fibrillation or atrial flutter
(documented by 12-lead ECG or a Holter recording) and eligible for 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 (NYHA Class ≥ II)
- Must be able to self-administer treatment.
- Either VKA treated or VKA naive.
VKA-treat patients must have received the VKA treatment for ≥3
months.
VKA-naïve patients must 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 (for
example, a patient treated with VKA for 40 days within the last 12
months) are not eligible for the study.
- Patients previously treated with ASA for stroke prevention are allowed
(and will switch to apixaban).
- Patients with screening Mini-mental state examination score (MMSE)
more than 24 (out of 30).
- Patient Re-enrollment: This study does not permit the re-enrollment of
a patient that has discontinued the study as a pre-treatment failure.
- Men and women ≥ 18 years of age.
- Women of childbearing potential (WOCBP) must use method(s) of
contraception based on the tables in Appendix 3.
- WOCBP must have a negative urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
the start of study medication.
- Women must not be breastfeeding.
- Men who are sexually active with WOCBP must use any contraceptive
method with a failure rate of less than 1% per year.
- Women who are not of childbearing potential (ie, who are
postmenopausal or surgically sterile; see Section 3.3.3 for the definition
of WOCBP) and azoospermic men do not require contraception. |
|
E.4 | Principal exclusion criteria |
1) Target Disease Exceptions
a) Atrial fibrillation or flutter due to reversible causes (e.g.
thyrotoxicosis, pericarditis)
b) Clinically significant (moderate or severe) mitral stenosis
c) Cardiac valvular disease requiring surgery
2) Medical History and Concurrent Diseases
a) Conditions other than atrial fibrillation that require chronic
anticoagulation (e.g., prosthetic mechanical heart valve, venous
thromboembolism; also see Section 3.4, Concomitant Treatments).
b) 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 oesophageal varices
•Recent ischemic stroke (within 7 days)
•Recent brain or spinal injury or intracranial haemorrhage
•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
c) Persistent, uncontrolled hypertension (systolic BP > 180 mm Hg,
and/or diastolic BP > 100 mm Hg)
d) Active infective endocarditis
e) Hepatic disease associated with coagulopathy and clinically relevant
bleeding risk
f) Active alcohol or drug abuse, or psychosocial reasons that make study
participation impractical.
g) Severe co-morbid condition with life expectancy ≤ 1 year
a) Severe renal insufficiency (creatinine clearance must be calculated -
Cockroft-Gault - in all patients; any patient with a calculated creatinine
clearance <15 ml/min is excluded) or patients undergoing dialysis.
b) ALT (alanine aminotransferase) or AST (aspartate aminotransferase)
> 2 times upper limit of normal or a total bilirubin > 1.5 times upper
limit of normal (unless an alternative causative factor [e.g., Gilbert's
syndrome] is identified)
c) Haemoglobin < 9 g/dL
d) Platelet count < 100,000/mm3
4) Allergies and Adverse Drug Reaction
a) Allergy or adverse reaction to apixaban or any of the excipients
5) Sex and Reproductive Status
a) Women who are pregnant or breast feeding
b) Women of child bearing potential (WOCBP, see Section 3.3.3 for
definition) who are unwilling to meet the study requirements for
pregnancy testing or are unwilling or unable to use an acceptable
method to avoid pregnancy.
c) Sexually active fertile men not willing to use effective birth control if
their partners are WOCBP
6) Prohibited Treatments and/or Therapies
a) See Section 3.4.1 of the protocol (Prohibited and/or Restricted
Treatments) for therapies which are prohibited at study entry
b) Patients previously included or currently enrolled in clinical trials of
apixaban
c) Required treatment with ASA > 165 mg/day
d) Simultaneous treatment with a thienopyridine (e.g., clopidogrel,
ticlopidine; see Section 3.4.2.1, Acetylsalicylic acid [ASA] and
Thienopyridines) or prasugrel or ticagrelor
e) Patients receiving rivaroxaban, dabigatran, or apixaban
f) Planned major surgery or/and invasive procedure
g) Planned atrial fibrillation or flutter ablation procedure
h) Planned cardioversion
7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a
psychiatric or physical (eg, infectious disease) illness
c) Use of an unapproved, investigational drug or device within the past
30 days or prior participation into an apixaban clinical study
d) Inability to comply with protocol visit and activity requirements
e) Patients unable to self-administer study medication
f) Patients who are hospitalized or scheduled to be hospitalized or for
whom treatment is administered by a third person (eg, nurse, relatives).
g) Patients in long term residential care. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the percentage of days with a correct execution of the apixaban dosing regimen during 24 weeks. This endpoint will be compared between the two study groups: Standard Of Care (SOC) information or additional education. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Within each study group, 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.
- Adherence to apixaban dosing regimen during the 24 to 48 weeks in continued additional education group, secondary SOC group, and primary SOC group.
- Risk factors indicative of non-adherence at 24 and 48 weeks.
- Serious adverse events and other AEs, including major bleeding (ISTH) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care Information vs. additional education programme |
|
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 100 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last Visit Last Subject (LVLS) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |