Status: Planned
First registered on:
16/11/2020
Last updated on:
16/11/2020
1. Study identification
EU PAS Register NumberEUPAS38060
Official titleDrug-drug interactions between dicloxacillin/flucloxacillin and DOACs
Study title acronym
Study typeObservational study
Brief description of the studyDirect oral anticoagulants (DOACs) are a group of anticoagulants that include dabigatran, rivaroxaban, apixaban, and edoxaban. They are used to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF) and as prophylaxis against deep vein thrombosis (DVT) and pulmonary embolism (PE). They were developed as alternatives to vitamin-K antagonists (VKA) such as warfarin, and studies have shown that they are just as safe and effective in prevention of stroke in patients with NVAF. DOACs are more convenient than warfarin due to wider therapeutic range meaning that routine blood tests are not required.
Previous studies have investigated co-administration of dicloxacillin and warfarin, which leads to higher risk of strokes and SE. Wether or not a similar association between DOACs and dicloxacillin/flucloxacillin exists, has never been assessed.
With this cohort study we aim to investigate if co-administration of dicloxacillin/flucloxacillin leads to increased risk of strokes or SE in patients using DOACs.
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
Department/Research groupUniversity of Southern Denmark Pharmacoepi center
Organisation/affiliationUniversity of Southern Denmark
Details of (Primary) lead investigator
Title Professor
Last name Pottegård
First name Anton
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?2
Countries in which this study is being conducted
International study
Denmark
Netherlands
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed13/11/2020
Start date of data collection01/01/2021
Start date of data analysis
Date of interim report, if expected
Date of final study report02/08/2021
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
OtherNone100
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Pottegård
First name Anton
Address line 1JB Winsløwsvej 19,2
Address line 2
Address line 3
CityOdense C
Postcode5000
CountryDenmark
Phone number (incl. country code)45-65503024
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Professor
Last name Pottegård
First name Anton
Address line 1JB Winsløwsvej 19,2
Address line 2
Address line 3
CityOdense C
Postcode5000
CountryDenmark
Phone number (incl. country code)45-65503024
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)J01CF05 (flucloxacillin)
Substance class (ATC Code)J01CF01 (dicloxacillin)
Substance class (ATC Code)B01AE07 (dabigatran etexilate)
Substance class (ATC Code)B01AF01 (rivaroxaban)
Substance class (ATC Code)B01AF03 (edoxaban)
Substance class (ATC Code)B01AF02 (apixaban)
Substance class (ATC Code)J01CE02 (phenoxymethylpenicillin)
7. Medical conditions to be studied
Medical condition(s)Yes
Ischaemic stroke
Systemic embolism
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
Other population
Renal impaired
Hepatic impaired
Immunocompromised
Pregnant women
9. Number of subjects
Estimated total number of subjects200000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Administrative database, e.g. claims database
Pharmacy dispensing records
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
To investigate if co-administration of dicloxacillin/flucloxacillin leads to increased risk of strokes or systemic embolism in patients using DOACs
Are there primary outcomes?Yes
To estimated the hazard ratios (HR) for the four DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with a 95% CI comparing the group treated with dicloxacillin/flucloxacillin vs. group treated with phenoxymethylpenicillin, and vs. no treatment with antibiotics.
Are there secondary outcomes?Yes
- To calculate number needed to treat for one additional patient to be harmed (NNTH)
- Performing subgroup analysis (age, sex, or intake of dicloxacillin or flucloxacillin)
- Extend follow-up period from 5-20 days to 5-30 days
- Analyze if indication for DOAC treatment had any influence
- Subgroup analysis excluding specific patient groups
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 day of prescription fill for dicloxacillin/flucloxacillin or phenoxymethylpenicillin is considered as the index date. They are followed from day 5 after the index date until day 20. Only the first outcome is included in the study.
15. Data analysis plan
Please provide a brief summary of the analysis method
Risks, hazard ratio using Cox regression, odds ratio using conditional logistic regression
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
None
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
Submitted
