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The Comparative Safety and Effectiveness of Dabigatran, Versus Rivaroxaban, and Apixaban Utilized in the Department of Defense Non-Valvular Atrial Fibrillation Patient Population: A Retrospective Database Analysis

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ClinicalTrials.gov Identifier: NCT03026556
Recruitment Status : Completed
First Posted : January 20, 2017
Results First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Collaborators:
Health ResearchTx, LLC (HRTX)
inVentiv Health Clinical (iVH)
United States Department of Defense (DOD)
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
The purpose of this study is to assess the safety and effectiveness of newly initiated dabigatran among patients diagnosed with non valvular atrial fibrillation (NVAF) in comparison to newly initiated rivaroxaban users and newly initiated apixaban users

Condition or disease Intervention/treatment
Atrial Fibrillation Drug: Dabigatran vs. Rivaroxaban Drug: Dabigatran vs. Apixaban

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Study Type : Observational
Actual Enrollment : 42534 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Safety and Effectiveness Study Comparing Dabigatran, Rivaroxaban & Apixaban in Non-valvular Atrial Fibrillation Patients Enrolled in the US Department of Defense Military Health System
Actual Study Start Date : December 29, 2016
Actual Primary Completion Date : August 23, 2017
Actual Study Completion Date : August 23, 2017


Group/Cohort Intervention/treatment
Dabigatran vs. Rivaroxaban
OAC treatment naïve NVAF patients with at least one prescription claim for dabigatran, rivaroxaban (new oral anticoagulant or NOAC).
Drug: Dabigatran vs. Rivaroxaban
observed for 6 years

Dabigatran vs. Apixaban
OAC treatment naïve NVAF patients with at least one prescription claim for dabigatran, or apixaban (new oral anticoagulant or NOAC).
Drug: Dabigatran vs. Apixaban
Observed for 6 years




Primary Outcome Measures :
  1. Stroke Overall (Hemorrhagic, Ischemic, Uncertain) [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of overall stroke (hemorrhagic, ischemic, uncertain) in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Length of Follow-up: The post-index follow-up period began the day following the NOAC index date and ended on whichever of the following occurred earliest:

    1. The day of discontinuation of the index NOAC exposure;
    2. The day before a switch to an anticoagulant different from the index exposure;
    3. The day before a change in dose for the index NOAC;
    4. The end of continuous eligibility of a patient in the health plan (disenrollment);
    5. The end of the study observation period; or
    6. The date of death of the patient.

  2. Overall Major Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of overall Major bleeding (Hemorrhagic Stroke, Major Intracranial Bleeding and Major Extracranial Bleeding) in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first.



Secondary Outcome Measures :
  1. Ischemic Stroke [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of ischemic stroke in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  2. Hemorrhagic Stroke [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of Hemorrhagic stroke in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first.


  3. Major Intracranial Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of major intracranial bleeding in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  4. Major Extracranial Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of major extracranial bleeding (Major GI bleeding, Major urogenital bleeding and Major other bleeding) in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  5. Major GI Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of major GI bleeding (Upper GI Bleeding and Lower GI Bleeding) in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  6. Major Urogenital Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of major urogenital bleeding in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first.


  7. Major Other Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of major other bleeding in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  8. Upper GI Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of Upper GI Bleeding in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  9. Lower GI Bleeding [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of Lower GI Bleeding in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  10. TIA [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of transient ischemic attack (TIA) in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first


  11. All-cause Mortality [ Time Frame: Baseline (July 1, 2010) until end of the observation period (June 30, 2016), 6 Years ]

    The event rate of all-cause mortality in patients matched on propensity scores without index year.

    Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort.

    Follow-up time was the time elapsed from the index date to the date of the outcome of interest, disenrollment, end of the observation period (available data), death, discontinuation of the NOAC, or switch to a different NOAC, whichever came first




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
NVAF patients, ≥18 years of age, enrolled within the DoD Military Health System, who have newly initiated dabigatran, rivaroxaban, or apixaban. Patients must be treatment naïve from OAC use prior to first (index) NOAC.
Criteria

Inclusion Criteria:

  • Age 18+ on index date
  • Patients must have been prescribed either dabigatran, rivaroxaban, or apixaban identified by pharmacy claim during the study period. The first dispensing date of either study drug will be defined as the index date;
  • Patients must be treatment naïve from all OAC use prior to the first NOAC prescription, during study period.
  • Patients must have at least 12 months of continuous eligibility prior to the index date;
  • Patients must have at least one diagnosis code of atrial fibrillation, defined as International Classification of Diseases (ICD)-9-CM diagnosis of 427.31 or ICD-10-CM diagnosis of I48.0, I48.1, I48.2, I48.91 on the index date or during the pre-index period.

Exclusion Criteria:

Less than 12 months of continuous eligibility in the pre-index period Any claim for OAC drug (oral use only) in the pre-index period Diagnosis of hyperthyroidism during the pre-index period

Having at least one claim for alternative indications; orthopedic procedures, Venous thromboembolism (VTE) (includes deep vein thrombosis (DVT ) & PE)) and the index NOAC prescription at the same time, or, the alternative indication for anticoagulant occurring within 3 months prior to index date in pre-period Having at least one claim with any of the following diagnoses or procedure codes in order to exclude patients with "transient" causes of Afib (3 months prior to index date in pre-period):

  • Cardiac surgery
  • Pericarditis
  • Myocarditis Having at least one medical claim with any of the following diagnoses or procedures codes in order to exclude patients with "valvular" Afib (pre-period):
  • Mitral stenosis
  • Mitral stenosis with insufficiency
  • Mitral valve stenosis and aortic valve stenosis
  • Mitral valve stenosis and aortic valve insufficiency
  • Diseases of other endocardial structures
  • Other and unspecified rheumatic heart diseases
  • Open heart valvuloplasty without replacement
  • Open and other replacement of unspecified heart valve
  • Open and other replacement of aortic valve
  • Open and other replacement of mitral valve
  • Open and other replacement of pulmonary valve
  • Open and other replacement of tricuspid valve
  • Heart valve replaced by transplant
  • Heart valve replaced by a mechanical device/prosthesis
  • Atrioventricular valve repair
  • Aortic valve valvuloplasty
  • Unlisted procedure, cardiac surgery
  • Implantation of catheter-delivered prosthetic aortic heart valve; open thoracic approach
  • Transthoracic cardiac exposure (e.g., sternotomy, thoracotomy, subxiphoid) for catheter-delivered aortic valve replacement; without cardiopulmonary bypass
  • Transthoracic cardiac exposure (e.g., sternotomy, thoracotomy, subxiphoid) for catheter-delivered aortic valve replacement; with cardiopulmonary bypass
  • Replacement, aortic valve, with cardiopulmonary bypass; with prosthetic valve other than homograft or stentless valve
  • Valvuloplasty, mitral valve, with cardiopulmonary bypass
  • Valvuloplasty, mitral valve, with cardiopulmonary bypass; with prosthetic ring
  • Valvuloplasty, mitral valve, with cardiopulmonary bypass; radical reconstruction, with or without ring
  • Replacement, mitral valve, with cardiopulmonary bypass
  • Implantation of catheter-delivered prosthetic pulmonary valve, endovascular approach
  • Replacement, pulmonary valve
  • Valvectomy, tricuspid valve, with cardiopulmonary bypass
  • Valvuloplasty, tricuspid valve; without ring insertion
  • Valvuloplasty, tricuspid valve; with ring insertion
  • Replacement, tricuspid valve, with cardiopulmonary bypass

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03026556


Locations
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United States, New Jersey
Inventiv Health
Princeton, New Jersey, United States, 08450
Sponsors and Collaborators
Boehringer Ingelheim
Health ResearchTx, LLC (HRTX)
inVentiv Health Clinical (iVH)
United States Department of Defense (DOD)
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03026556     History of Changes
Other Study ID Numbers: 1160-0274
First Posted: January 20, 2017    Key Record Dates
Results First Posted: June 3, 2019
Last Update Posted: June 3, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Rivaroxaban
Apixaban
Dabigatran
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants