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A Nationwide Observational Study Looking at Effectiveness and Bleeding Complications of NOACs vs. VKA in Non-valvular Atrial Fibrillation Patients. (PROTECT-AF)

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ClinicalTrials.gov Identifier: NCT03715725
Recruitment Status : Active, not recruiting
First Posted : October 23, 2018
Last Update Posted : April 18, 2019
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer

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).

Condition or disease Intervention/treatment
Non-valvular Atrial Fibrillation Drug: Rivaroxaban (Xarelto, BAY59-7939) Drug: Apixaban (Eliquis) Drug: Dabigatran etexilate (Pradaxa) Drug: Warfarin (Marevan)

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Study Type : Observational
Estimated Enrollment : 70000 participants
Observational Model: Cohort
Time Perspective: Retrospective
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
Actual Study Start Date : October 31, 2018
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Registry cohort
Registries in Norway are nation-wide and provision of the information is mandatory, which eliminates the risk of both selection and re-call bias. The large and detailed dataset also makes it possible to adjust for other risk factors on which information is available.
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Administration according to clinical practice

Drug: Apixaban (Eliquis)
Administration according to clinical practice

Drug: Dabigatran etexilate (Pradaxa)
Administration according to clinical practice

Drug: Warfarin (Marevan)
Administration according to clinical practice

Electronic Medical Records (EMR) cohort
Patients with NVAF diagnosis will be identified through extraction of patient-level data from EMRs from a number of hospitals in Norway, in order to describe these patients more closely regarding their clinical characteristics that are not available in nation-wide registers (e.g., in-patient treatments, anthropometric data and laboratory test results).
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Administration according to clinical practice

Drug: Apixaban (Eliquis)
Administration according to clinical practice

Drug: Dabigatran etexilate (Pradaxa)
Administration according to clinical practice

Drug: Warfarin (Marevan)
Administration according to clinical practice




Primary Outcome Measures :
  1. Ischemic stroke [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]

    Ischemic stroke is defined by the following ICD10 (International Classification of Diseases) codes:

    I63x: Cerebral infarction


  2. Intracranial hemorrhage [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]

    Intracranial haemorrhage (ICH) is defined by the following ICD10 codes:

    I60x Subarachnoid haemorrhage I61x Intracerebral haemorrhage I62x Other non-traumatic intracranial haemorrhage



Secondary Outcome Measures :
  1. Overall stroke [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]

    Overall stroke is defined by the following ICD10 codes:

    I60x: Subarachnoid haemorrhage I61x: Intracerebral haemorrhage I62x: Other nontraumatic intracranial haemorrhage I63x: Cerebral infarction I64x: Stroke, not specified as haemorrhage or infarction


  2. Systemic embolism [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]

    Systemic embolism is defined by the following ICD10 codes:

    I74x: Arterial embolism and thrombosis


  3. Myocardial infarction [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]

    Myocardial infarction is defined by the following ICD10 codes:

    I21x: Acute myocardial infarction I22x: Subsequent myocardial infarction


  4. All-cause mortality [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]
  5. Major bleeding [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]
    As defined by Cunningham algorithm and Internation Society of Thrombosis and Hemostasis (ISTH) for EMR cohort.

  6. Demographic characteristics [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]
  7. Clinical characteristics [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]
    Age, gender, CHA2DS2-VASc and HAS-BLED score, bleeding history, concomitant medications and co-morbidities

  8. Drug utilization patterns [ Time Frame: Retrospective analysis from 1 January 2014 to 30 June 2018 ]


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
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).
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.

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): NCT03715725


Locations
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Norway
Many locations
Multiple Locations, Norway
Sponsors and Collaborators
Bayer
Janssen Research & Development, LLC

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03715725     History of Changes
Other Study ID Numbers: 19468
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
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
Warfarin
Rivaroxaban
Dabigatran
Apixaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action