Clinical trial NCT04001166: Pharmacogenomics of Antithrombotic Drugs -a Register Linkage Study With National Registries and Biobanks in Finland
Official title: Pharmacogenomics of Antithrombotic Drugs (PreMed PGx Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Individuals With a Disease of Cardiovascular System
Lead sponsor: VTT Technical Research Centre of Finland
Sponsor class: OTHER
Collaborators: name: Helsinki Biobank
name: THL Biobank
name: Auria Biobank
name: Hospital District of Helsinki and Uusimaa
name: Hospital District of Southwestern Finland
name: Finnish Institute for Health and Welfare
name: Social Insurance Institution, Finland
First posted: 2019-06-27
Enrollment: 7005
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of adults diagnosed with a disease of cardiovascular system and genotyped for variants in CYP2C9 and VKORC1, and who have used antithrombotic drugs between January 1st 2007 - December 31st 2018.

Brief summary: This is a retrospective cohort study linking data from Finnish Biobanks (Helsinki Biobank, Auria Biobank and THL Biobank), laboratory databases, and national registries of Social Insurance Institution of Finland (Kela) and the National Institute of Health and Welfare (THL) to investigate pharmacogenomics of antithrombotic drugs in the Finnish population. The purpose of the study is to assess clinical and economic aspects of using genomic data in the context of antithrombotic drug therapy.

Based on earlier research, data regarding variant alleles in CYP2C9 and VKORC1 will be used in the primary analyses. Individuals with and without specific variant alleles are compared in respect to their clinical response to warfarin therapy. Warfarin-treated individuals are also analysed in relation to other clinical outcomes and a wide range of healthcare encounters.

The explorative part of the study will employ data-driven classification methods to explore genotype-phenotype associations for a larger group of antithrombotic drugs including direct oral anticoagulants, clopidogrel and heparins and possible interactions with other drugs. In this part, 26 gene variants identified in literature will be used.

The retrospective follow-up time for the study participants is from January 2007 to December 2018, or 2 years prior the first anticoagulant drug is purchased until 6 months after the last purchase.


Eligibility criteria: Inclusion Criteria:

* Genotyped for CYP2C9/rs1799853, CYP2C9/rs1057910 and VKORC1/rs9923231
* Diagnosed with at least one of the following:

  * Atrial Fibrillation and Flutter (I48)
  * Ischemic Heart Disease (I20-I25)
  * Cerebrovascular disease (I63,I65,I66, 167.2, I69.3-I69.8)
  * Atherosclerosis (I70)
  * Pulmonary embolism (I26)
  * Phlebitis and thrombophlebitis (I80)
  * Portal vein thrombosis (I81)
  * Other venous embolism and thrombosis (I82)
* Purchased at least one of the following drugs between January 1st 2007 - December 31st 2018:

  * Anticoagulants: Warfarin, Dabigatran, Apixaban, Rivaroxaban, Edoxaban, Heparin, Enoxaparin, Dalteparin
  * Antiplatelets: Clopidogrel, Ticagrelor, Acetylsalicylic acid

Exclusion Criteria:

* Permanent residence in Finland less than 12 months during the follow-up period
* Purchase of any of the antithrombotic drugs listed above between January 1st 2005 - December 31st 2006

Primary outcomes:
measure: Incidence of bleeding complications
timeFrame: During warfarin treatment and beyond 6 months after the treatment
Secondary outcomes:
measure: Time in Therapeutic Range (TTR)
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Time to reach therapeutic range
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Time-weighted mean INR
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Incidence of outpatients visits
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Incidence of laboratory visits
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: The number of laboratory tests
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Incidence of emergency room (ER) visits
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Indicidence of hospital admissions
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: The number of hospital inpatient days
timeFrame: During warfarin treatment and beyond 6 months after the treatment
measure: Incidence of medical procedures
timeFrame: During warfarin treatment and beyond 6 months after the treatment
Other outcomes:
Locations:
city: Multiple Locations
country: Finland
facility: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Study officials:
affiliation: VTT Technical Research Centre of Finland
name: Jari Ahola
role: STUDY_DIRECTOR
affiliation: VTT Technical Research Centre of Finland
name: Mark van Gils, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vuorinen AL, Lehto M, Niemi M, Harno K, Pajula J, van Gils M, Lahteenmaki J. Pharmacogenetics of Anticoagulation and Clinical Events in Warfarin-Treated Patients: A Register-Based Cohort Study with Biobank Data and National Health Registries in Finland. Clin Epidemiol. 2021 Mar 8;13:183-195. doi: 10.2147/CLEP.S289031. eCollection 2021.