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Safety and Effectiveness of Oral Anticoagulants in Patients With Non-valvular Atrial Fibrillation (CER3)

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ClinicalTrials.gov Identifier: NCT03570047
Recruitment Status : Completed
First Posted : June 26, 2018
Results First Posted : November 4, 2019
Last Update Posted : November 4, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
An anticoagulation therapy is a critical treatment to prevent thromboembolism in non-valvular AF (NVAF) patients. Warfarin, a vitamin K antagonist, is the first oral anticoagulant approved for the treatment for prevention of thromboembolism and it had long been the only oral anticoagulant until the first non-vitamin K antagonist oral anticoagulants (NOACs). However, its safety and effectiveness remains unknown in real-world clinical practice in Japan

Condition or disease
Non-valvular Atrial Fibrillation

Detailed Description:
An anticoagulation therapy is a critical treatment to prevent thromboembolism in non-valvular AF (NVAF) patients. Warfarin, a vitamin K antagonist, is the first oral anticoagulant approved for the treatment for prevention of thromboembolism and it had long been the only oral anticoagulant until the first non-vitamin K antagonist oral anticoagulants (NOACs). However, its safety and effectiveness remains unknown in real-world clinical practice in Japan. This study will evaluate the risk of stroke/SE as well as the risk of bleeding in the real world settings in Japan in patients with NVAF who initiated any of OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin)

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Study Type : Observational
Actual Enrollment : 73989 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: SAFETY AND EFFECTIVENESS EVALUATION OF PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION TREATED WITH OACS: COMPARISON BETWEEN NOACS AND WARFARIN (CER3)
Actual Study Start Date : May 8, 2018
Actual Primary Completion Date : October 31, 2018
Actual Study Completion Date : October 31, 2018

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Event Rate Per 100 Participant-Years For First Occurrence of Stroke and Systemic Embolism Events After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of stroke and systemic embolism events after index date was reported. Stroke events included the composite of any ischemic and any hemorrhagic stroke events (non-traumatic extradural hemorrhage). Systemic embolism events were defined as any of the following: abdominal aortic embolism, aortic embolism, acute arterial occlusive disease of arteries of upper extremities, femoral arterial occlusion and acute arterial occlusive disease of arteries of lower extremities, iliac artery embolism, hepatic artery embolism, thromboembolism, embolic infarction, aortic embolism, subclavian artery stenosis. Index date was defined as date of first prescription of any OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  2. Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of major bleeding event after index date was reported. Major bleeding after index date was identified using hospital claims which had a bleeding diagnosis code as the first listed in International Statistical Classification of Diseases and Related Health Problems (ICD)-10 diagnosis code. An event occurrence of major bleeding was defined as that appears as "21: Disease name behind hospitalization" in database. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  3. Event Rate Per 100 Participant-Years For First Occurrence of Any Bleeding Event After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of any bleeding event after index date was reported. Any bleeding was defined using ICD-10 diagnosis codes and participants were considered to have "any bleeding" if pre-defined bleeding-associated ICD-10 diagnosis codes appeared in the records. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.


Secondary Outcome Measures :
  1. Event Rate Per 100 Participant-Years For First Occurrence of Ischemic Stroke After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of ischemic stroke after index date was reported. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  2. Event Rate Per 100 Participant-Years For First Occurrence of Hemorrhagic Stroke After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of hemorrhagic stroke after index date was reported. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  3. Event Rate Per 100 Participant-Years For First Occurrence of Systemic Embolism Events After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of systemic embolism events after index date was reported. Systemic embolism events included any of the following: abdominal aortic embolism, aortic embolism, acute arterial occlusive disease of arteries of upper extremities, femoral arterial occlusion and acute arterial occlusive disease of arteries of lower extremities, iliac artery embolism, hepatic artery embolism, thromboembolism, embolic infarction, aortic embolism, subclavian artery stenosis. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  4. Event Rate Per 100 Participant-Years For First Occurrence of Major Gastrointestinal Bleeding Events After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of major gastrointestinal bleeding events after index date was reported. Major gastrointestinal bleeding after index date was identified using hospital claims which had a gastrointestinal bleeding diagnosis code as the first listed ICD-10 diagnosis code. An event occurrence of major bleeding was defined as that appears as "21: Disease name behind hospitalization" in database. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  5. Event Rate Per 100 Participant-Years For First Occurrence of Any Gastrointestinal Bleeding Event After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of any gastrointestinal bleeding event after index date was reported. Any gastrointestinal bleeding was defined by ICD-10 diagnosis codes. If participants had ICD-10 diagnosis codes which suggest bleeding from the gastrointestinal tract, they were considered to have any gastrointestinal bleeding. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  6. Event Rate Per 100 Participant-Years For First Occurrence of Major Intracranial Hemorrhage Events After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of major intracranial hemorrhage events after index date was reported. Major intracranial hemorrhage was defined by ICD-10 diagnosis codes and participants were considered to have "major intracranial hemorrhage" if pre-defined major intracranial hemorrhagic-associated ICD-10 diagnosis codes appeared in the records. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.

  7. Event Rate Per 100 Participant-Years For First Occurrence of Any Intracranial Hemorrhage Event After Index Date [ Time Frame: During the observation period of approximately 7 years ]
    Event rate per 100 participant-years for first occurrence of any intracranial hemorrhage event after index date was reported. Any intracranial hemorrhage was defined by ICD-10 diagnosis codes and participants were considered to have "any intracranial hemorrhagic event" if pre-defined any intracranial hemorrhagic-associated ICD-10 diagnosis codes appeared in the records. Index date was defined as the date of the first prescription of any of OACs (warfarin, apixaban, dabigatran, rivaroxaban or edoxaban) during the observation period of approximately 7 years (2011-2017). Pseudo datasets refers to number derived using IPTW method and are different from the actual participants included in the reporting arm.



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
Patients with NVAF who initiated any of oral anti-coagulants
Criteria

Inclusion criteria

Patients must meet all of the following criteria to be eligible for the study:

  1. Diagnosed with AF anytime in the baseline period or on the index date, also have definitive diagnosis of AF anytime in the baseline period, on the index date, or post-index period.
  2. Prescribed one of the index OACs (apixaban, dabigatran, edoxaban, rivaroxaban or warfarin) on or after the day of AF diagnosis. The first observed prescription will be used to identify the patient's index date and treatment cohort
  3. No use of the any OACs during the baseline period (the 180 days before the index date)
  4. Age of 18 years or older on the index date.

Exclusion criteria

Patients meeting any of the following criteria will not be included in the study:

1. Having a diagnosis of valvular atrial fibrillation, post-operative atrial fibrillation, rheumatic atrial fibrillation or mechanical-valvular atrial fibrillation during the baseline and post-index period 2. Having a cardiac surgery procedure record during the baseline period 3. Having a joint replacement procedure record during the baseline period 4. Having a procedure of prosthetic heart valve during the baseline period 5. Having a diagnosis of venous thromboembolism during the baseline period 6. Female patients with pregnancy during the follow-up period 7. Patients prescribed "off-label" doses of OACs (per Japanese package insert of each OAC) or patients treated with OAC but in "off-label" or "contraindicated" manners.

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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): NCT03570047


Locations
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Japan
Pfizer Japan
Tokyo, Japan
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] May 8, 2018
Statistical Analysis Plan  [PDF] March 14, 2018


Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03570047     History of Changes
Other Study ID Numbers: B0661120
CER3 ( Other Identifier: Alias Study Number )
First Posted: June 26, 2018    Key Record Dates
Results First Posted: November 4, 2019
Last Update Posted: November 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Keywords provided by Pfizer:
Non-valvular atrial fibrillation, NVAF
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes