Status: Planned
First registered on:
10/01/2022
Last updated on:
20/10/2022
1. Study identification
EU PAS Register NumberEUPAS45073
Official titleComparative Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation in the UK
Study title acronym
Study typeObservational study
Brief description of the studyThis study aims to evaluate the incidence of stroke and other outcomes in association with direct oral anticoagulants (DOACs) as compared to each other (i.e., direct comparisons) among patients with nonvalvular atrial fibrillation (AFib) in the UK. Individual DOACs of interest include apixaban, rivaroxaban, edoxaban, and dabigatran.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsAetion
Department/Research group
Organisation/affiliationAetion
Details of (Primary) lead investigator
Title Dr
Last name Ali
First name Ayad
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed08/06/2021
Start date of data collection01/09/2021
Start date of data analysis
Date of interim report, if expected
Date of final study report28/02/2022
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government body
Research councils
EU funding scheme
OtherAetion100
5. Contact details for enquiries
Scientific Enquiries
Title Ms
Last name Amanda
First name Patrick
Address line 15 Penn Plaza
Address line 27th Floor
Address line 3
CityNew York
Postcode10001
CountryUnited States
Phone number (incl. country code)018448238466
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Ms
Last name Ashley
First name Jaksa
Address line 15 Penn Plaza
Address line 27th Floor
Address line 3
CityNew York
Postcode10001
CountryUnited States
Phone number (incl. country code)018448238466
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)B01AF02 (apixaban)
Substance class (ATC Code)B01AF01 (rivaroxaban)
Substance class (ATC Code)B01AF03 (edoxaban)
Substance class (ATC Code)B01AE07 (dabigatran etexilate)
7. Medical conditions to be studied
Medical condition(s)Yes
Atrial fibrillation
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects13991
Additional information
Data extract included 13,991 patients. Additional exclusion criteria will be applied and final cohort size will be <13,991.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Routine primary care electronic patient registry
11. Scope of the study
What is the scope of the study?
Effectiveness evaluation
Primary scope : Effectiveness evaluation
12. Main objective(s)
What is the main objective of the study?
This study aims to evaluate the incidence of stroke and other outcomes in association with direct oral anticoagulants (DOACs) as compared to each other (i.e., direct comparisons) among patients with nonvalvular atrial fibrillation (AFib) in the UK. Individual DOACs of interest include apixaban, rivaroxaban, edoxaban, and dabigatran.
Are there primary outcomes?Yes
The primary objective is to:
Estimate the incidence rates and evaluate the association of stroke (ischemic or hemorrhagic) for patients with nonvalvular AFib who initiated apixaban compared to rivaroxaban
Are there secondary outcomes?Yes
The secondary objectives are to:
Compare the incidence rates of stroke for patients who initiated:
apixaban compared to edoxaban, dabigatran, and DOACs class;
rivaroxaban compared to edoxaban, dabigatran, and DOACs class;
edoxaban compared to DOACs class;
dabigatran compared to DOACs class;
Compare the incidence rates of secondary outcomes for the each head to head comparison.
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
The follow-up period will include all available time after study index date. Patients will be followed in an “intention to treat” and "as treated" approach a from their index date until the occurrence of events listed in the protocol.
15. Data analysis plan
Please provide a brief summary of the analysis method
In each comparison cohort, propensity score matching between exposure groups will be performed using 1:1 nearest neighbor matching without replacement with a maximum matching caliper of 0.01. In addition to graphical depictions of propensity score distributions, the absolute standardized differences (ASD) in proportions and means of baseline characteristics will be estimated to examine comparability of exposure groups.
Cox proportional hazards regression (outcomes model) will be used to estimate hazard ratios and 95% CI for each outcome after propensity score matching. The incidence of stroke and secondary outcomes will be compared between individual DOACs in primary and secondary comparisons as mutually exclusive cohorts.
High-dimensional propensity score (HdPS) analysis will be used as a sensitivity analysis to estimate the association between treatment with DOACs and the primary outcome of stroke.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
Jaksa A, Gibbs L, Kent S, Rowark S, Duffield S, Sharma M, Kincaid L, Ali AK, Patrick AR, Govil P, Jonsson P, Gatto N. Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study. BMJ Open. October 2022;12(10):e064662.https://pubmed.ncbi.nlm.nih.gov/36253039/
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
