Clinical trial NCT03715725: A Nationwide Observational Study Looking at Effectiveness and Bleeding Complications of NOACs vs. VKA in Non-valvular Atrial Fibrillation Patients.
Official title: A Post-marketing Retrospective Non-interventional Study Using Nationwide Registries and Electronic Medical Records to Investigate the Real-life Effectiveness and Major Bleeding Complications of Oral Anticoagulants in Norwegian Non-valvular Atrial Fibrillation Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Non-valvular Atrial Fibrillation
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2018-10-23
Enrollment: 70000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will comprise all adult OAC naïve NVAF patients in Norway who filled a prescription for an OAC (rivaroxaban, apixaban, dabigatran, warfarin) in the study period, defined as from 1 January 2014 to 30 June 2018 (or later depending on availability of data) and followed until outcome of interest, the end of the study period or death. This initiation of an OAC is the index event and requires that there is no previous prescription dispensed for an OAC in the preceding 365 days (from end date of OAC supply to date of new OAC dispensation).

Brief summary: Using mandatory nationwide registries and possibly hospital electronic medical records in Norway, the researchers want to understand how well a group of drugs called "non-vitamin K antagonist oral anticoagulants" (rivaroxaban - Xarelto; apixaban - Eliquis; dabigatran - Pradaxa) works in patients with non-valvular atrial fibrillation (this is a condition when the heart beats irregularly) compared to another older drug, a vitamin K antagonist oral anticoagulants (warfarin) and how safe these drugs are. The primary objective of the study is to assess the occurence of an ischemic stroke (a condition when an artery that brings blood to the brain is blocked) and intracranial hemorrhage (a serious condition when a diseased blood vessel within the brain bursts).


Eligibility criteria: Inclusion Criteria:

Registry cohort (Cohort 1)

Cohort 1a:

* Age ≥18 at the date of first OAC (Oral Anti-Coagulants) dispensation (index date)
* Diagnosed with atrial fibrillation or flutter in the period 5-year pre-index period. Defined as ICD10 codes; I480 (paroxysmal AF), I481 (persisting AF), I482 (chronic AF), I483 (typical AF), I484 (atypical AF) or I489 (unspecified atrial fibrillation or flutter) as given by either NPR (Norwegian Patient Register) or as a OAC (warfarin, dabigatran, rivaroxaban or apixaban) dispensed on the reimbursement code for AF in NorPD (Norwegian Prescription Database) (ICD10 I48 or ICPC-2 K78)
* Dispensation of a first-time prescription for an OAC during the study period 1 January 2014 to 31 May 2018. This initiation of an OAC is the index event and requires that there is no previous prescription for any OAC in the preceding 365 days (counted from the date of the first dispensation backward to the end of OAC supply).

Cohort 1b:

* Age ≥18 at the beginning of the study period (1 January 2014).
* Diagnosed with atrial fibrillation or flutter prior or during the study period. Defined as ICD10 codes; I480 (paroxysmal AF), I481 (persisting AF), I482 (chronic AF), I483 (typical AF), I484 (atypical AF) or I489 (unspecified atrial fibrillation or flutter) as given by NPR.
* No dispensation of a prescription for an OAC (warfarin, dabigatran, rivaroxaban or apixaban) during the study period 1 January 2014 to 30 June 2018. The index event will be the beginning of the study period (1 January 2014) and requires that there is no previous prescription for an OAC in the preceding 365 days.

EMR cohort (Cohort 2):

* Age ≥18 at the date of first OAC dispensation (index date).
* Diagnosed with atrial fibrillation or flutter in the 5-year pre-index period defined as one of the following ICD10 codes in the EMRs obtained from the hospitals in the South-Eastern Health Region; I480 (paroxysmal AF), I481 (persisting AF), I482 (chronic AF), I483 (typical AF), I484 (atypical AF) or I489 (unspecified atrial fibrillation or flutter).
* Dispensation of a first-time prescription for an OAC (warfarin, dabigatran, rivaroxaban or apixaban) during the study period 1 January 2014 to 31 May 2018. This initiation of an OAC is the index event and requires that there is no previous prescription of any OAC in the preceding 365 days (counted from the date of the first dispensation backward to the end of OAC supply).

Exclusion Criteria:

* Valvular atrial fibrillation defined as presence of ICD10 codes in NPR; I05.2 mitral stenosis with insufficiency, I05.8 other mitral valve diseases (mitral (valve) failure), I342 (non-rheumatic mitral valve stenosis), Z952 (presence of prosthetic heart valve) and procedure codes FKD (prosthetic replacement of mitral valve), FKA (Repair of mitral valve for stenosis), FKB (Annuloplasty of mitral valve for insufficiency), FKC (Repair of mitral valve for insufficiency), FKW (Other operations on mitral valve) and FMD (replacement of aortic valve).
* Deep Venous Thrombosis (DVT) as defined by ICD10 codes I80 (Phlebitis and thrombophlebitis), Pulmonary Embolism (PE) as defined by ICD10 code I26 or I82 (other venous embolism and thrombosis), Other venous embolism and thrombosis within last 6 months before index date.
* Knee and/or hip replacement surgery (NCSP (Nordic Classification of Surgical Procedures) procedure codes; NGB, NGC, NFB or NFC) 5 weeks before index date.

Primary outcomes:
measure: Ischemic stroke
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Intracranial hemorrhage
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
Secondary outcomes:
measure: Overall stroke
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Systemic embolism
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Myocardial infarction
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: All-cause mortality
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Major bleeding
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Demographic characteristics
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Clinical characteristics
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
measure: Drug utilization patterns
timeFrame: Retrospective analysis from 1 January 2014 to 30 June 2018
Other outcomes:
Locations:
city: Multiple Locations
country: Norway
facility: Many Locations
Study officials:
References: