Direct Oral Anticoagulants and Venous Thromboembolism

NCT02833987 | Completed

• 1 other identifier: Q14-02
• Study Type: observational
• Target: 59,525
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether use of direct oral anticoagulants (DOACs) is associated with an increased risk of major bleeding compared to warfarin use, for the treatment of venous thromboembolism (VTE). The investigators will carry out separate population based cohort studies using health administrative databases in eight jurisdictions in Canada, the UK and the US. Cohorts will be defined by the initiation of a DOAC or warfarin on or after January 1, 2009, with an incident diagnosis of VTE having occurred within 30 days prior to the date of the prescription for the DOAC or warfarin. Follow-up will continue until a hospitalization or emergency department visit for a major bleed. The results from separate sites will be combined to provide an overall assessment of the risk of major bleeding in DOAC users.

Conditions

Venous Thromboembolism; Major Bleed

Keywords

Direct oral anticoagulants; Safety; Major bleed; Adverse events

Outcome Measures

Primary Outcomes (1)

• Major bleed

  Patients hospitalized or visiting the emergency department for a major bleed recorded as the most responsible diagnosis in either the discharge abstract or hospitalization record with the following ICD codes: ICD-9 codes: 430, 431, 432.0, 432.1, 432.9, 531.0, 531.2, 531.4, 531.6, 532.0, 532.2, 532.4, 532.6, 533.0, 533.2, 533.4, 533.6, 534.0, 534.2, 534.4, 534.6, 578.0, 578.1, 578.9, 569.3, 578.1, 578.9 ICD-10 codes: I60, I61, I62.0, I62.1, I62.9, K92.0, K92.1, I85.0, I98.20, I98.3, K22.10, K22.12, K22.14, K22.16, K25.0, K25.2, K25.4, K25.6, K26.0, K26.2, K26.4, K26.6, K27.0, K27.2, K27.4, K27.6, K28.0, K28.2, K28.4, K28.6, K29.0, K63.80, K31.80, K55.20, K62.5, K92.2, N02.0, N02.1, N02.2, N02.3, N02.4, N02.5, N02.6, N02.7, N02.8, N02.9, K66.1, N93.8, N93.9, N95.0, R04.1, R04.2, R04.8, R04.9, R31.0, R31.1, R31.8, R58, D68.3, H35.6, H43.1, H45.0, M25.0

  Patients will be followed from the date of the first DOAC or warfarin prescription (study cohort entry) to a hospitalization or emergency department visit for a major bleed, censoring, or for up to 3 months, whichever occurred first.

Secondary Outcomes (1)

• All-cause mortality

  Patients were followed from the date of the first DOAC or warfarin prescription (study cohort entry) until death, censoring or for up to 3 months.

Study Arms (2)

Treated with direct oral anticoagulants (DOACs)

Patients who received a new prescription for a DOAC (apixaban, dabigatran, or rivaroxaban) in the 30 days following the date of an incident VTE diagnosis, and did not have a previous prescription for a DOAC or warfarin in the year prior to the date of the new prescription.

Drug: Apixaban (ATC B01AF02); Drug: Dabigatran (ATC B01AE07); Drug: Rivaroxaban (ATC B01AF01)

Treated with warfarin

Patients who received a new prescription for warfarin in the 30 days following the date of an incident VTE diagnosis, and did not have a previous prescription for a DOAC or warfarin in the year prior to the date of the new prescription.

Drug: Warfarin (ATC B01AA03)

Interventions

Apixaban (ATC B01AF02) DRUG

Exposure to apixaban (ATC B01AF02) will be defined as a new prescription for apixaban in the 30 days following the date of an incident VTE diagnosis.

Treated with direct oral anticoagulants (DOACs)

Dabigatran (ATC B01AE07) DRUG

Exposure to dabigatran (ATC B01AE07) will be defined as a new prescription for dabigatran in the 30 days following the date of an incident VTE diagnosis.

Treated with direct oral anticoagulants (DOACs)

Rivaroxaban (ATC B01AF01) DRUG

Exposure to rivaroxaban (ATC B01AF01) will be defined as a new prescription for rivaroxaban in the 30 days following the date of an incident VTE diagnosis.

Treated with direct oral anticoagulants (DOACs)

Warfarin (ATC B01AA03) DRUG

Exposure to warfarin (ATC B01AA03) will be defined as a new prescription for warfarin in the 30 days following the date of an incident VTE diagnosis.

Treated with warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In each jurisdiction, the investigators will assemble a study cohort that includes all patients aged 18 years or older with a new prescription for a DOAC or warfarin between January 1, 2009 and 180 days prior to the end date of data availability within that jurisdiction and with an incident diagnosis of VTE within 30 days prior to the date of the cohort entry prescription.

You may qualify if:

• Patients with a new prescription for a DOAC or warfarin that had an incident diagnosis of VTE within the 30 days prior to the date of the prescription
• Patients at least 18 years of age (except Nova Scotia, Ontario, and Alberta, where patients will be at least 66 years of age)
• Patients with at least 1 year of history in the database

You may not qualify if:

• Patients with a diagnosis of VTE or atrial fibrillation ≤335 days prior to the incident VTE diagnosis
• Patients that received a prescription for a DOAC or warfarin within 1 year prior to the date of the cohort entry
• Patients who received prescriptions for both a DOAC and warfarin on the date of cohort entry

Sponsors & Collaborators

• Canadian Network for Observational Drug Effect Studies, CNODES: lead
• Drug Safety and Effectiveness Network, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

Location

Related Publications (1)

• Jun M, Lix LM, Durand M, Dahl M, Paterson JM, Dormuth CR, Ernst P, Yao S, Renoux C, Tamim H, Wu C, Mahmud SM, Hemmelgarn BR; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study. BMJ. 2017 Oct 17;359:j4323. doi: 10.1136/bmj.j4323.

  PMID: 29042362 RESULT

Related Links

• This organization's website describing general functions, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

apixaban; Dabigatran; Rivaroxaban; Warfarin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Officials

• Brenda Hemmelgarn, MD, PhD

  Department of Community Health Sciences, University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2016
• First Posted: July 15, 2016
• Study Start: March 1, 2015
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: January 11, 2018

Record last verified: 2018-01

Locations

CA (1)