Study type

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(B01AE07) dabigatran etexilate
dabigatran etexilate
(B01AF01) rivaroxaban
rivaroxaban
(B01AF02) apixaban
apixaban
(B01AF03) edoxaban
edoxaban
(J01CE02) phenoxymethylpenicillin
phenoxymethylpenicillin
(J01CF01) dicloxacillin
dicloxacillin
(J01CF05) flucloxacillin
flucloxacillin

Medical condition to be studied

Ischaemic stroke
Embolism arterial
Population studied

Age groups

  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)
      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Special population of interest

Hepatic impaired
Immunocompromised
Pregnant women
Renal impaired

Estimated number of subjects

200000
Study design details

Main study objective

To investigate if co-administration of dicloxacillin/flucloxacillin leads to increased risk of strokes or systemic embolism in patients using DOACs

Outcomes

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. - 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

Data analysis plan

Risks, hazard ratio using Cox regression, odds ratio using conditional logistic regression