Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Pratice (Netherlands)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Bayer
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01947985
First received: September 11, 2013
Last updated: April 29, 2016
Last verified: April 2016
  Purpose
This prospective cohort study will provide information about: characteristics of Rivaroxaban use in patients who are prescribed Rivaroxaban for the first time compared to patients who are prescribed Acenocoumarol for the first time, the occurrence of intracranial haemorrhage, gastrointestinal and urogenital bleeding, and the occurrence of non-infective liver disease.

Condition Intervention
Venous Thrombosis
Pulmonary Embolism
Atrial Fibrillation
Acute Coronary Syndrome
Drug: Rivaroxoban (Xarelto, Bay59-7939)
Drug: Standard of care

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Proposed Pharmacoepidemiological Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Pratice in the Netherlands.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Descriptive analysis of demographic and clinical characteristics of patients who are prescribed oral rivaroxaban for the first time in comparison with those who are prescribed standard of care for the first time [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
    Age and sex distribution at index date Proportion of patients defined as naïve, non-naïve, recent switchers and distant switchers Type and estimated duration of other anticoagulant use among the non-naïve group and for all patients Number of pregnancies and pregnancy outcomes' Use of specific prescribed medications confirming ACS indication Use of other prescribed medications Renal disease based on in- and outpatient diagnoses Hospital admissions for bleeding Healthcare utilization (e.g. number of hospital admissions). Smoking status Body mass index (BMI)

  • Characteristics of rivaroxaban use in comparison with standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
    Estimated dose of index drug at index date and estimated duration of treatment Where available, the diagnosis associated with the prescribing of the index drug (where not available, estimated dose and duration of index drug will be used as a proxy for the associated diagnosis among rivaroxaban users) Dispensed amount (can be used to estimate duration of treatment)

  • Safety: occurrence of intracranial haemorrhage leading to hospitalization among users of rivaroxaban in comparison with individuals receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]

    Cases of intracranial haemorrhage will be identified in patients admitted to the hospital that meet the criteria for one of the three following categories:

    Incident cases of intracerebral haemorrhage Incident cases of subarachnoid haemorrhage incident cases of epidural, dural, subdural and arachnoid haemorrhage Potential cases will be identified by hospital discharge diagnoses


  • Safety: occurrence of gastrointestinal bleeding leading to hospitalization among users of rivaroxaban in comparison with individuals receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]

    A patient will have to meet the following criteria to be considered a case of gastrointestinal bleeding:

    The specific site of bleeding originating in the upper or lower gastrointestinal tract or, more specifically, in the oesophagus, stomach, duodenum, jejunum, ileum, colon or rectum.

    For upper gastrointestinal bleeding, the lesion type being erosion, gastritis, duodenitis or peptic (gastric or duodenal) ulcer.

    The lesion type being NOT related to cancer. Cases will be identified by hospital discharge diagnoses (ICD-9-CM).


  • Safety: occurrence urogenital bleeding leading to hospitalization among users of rivaroxaban in comparison with individuals receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]

    A patient will have to be admitted to the hospital for urogenital bleeding, i.e. the specific site of bleeding originating in the urogenital tract.

    Cases will be identified by hospital discharge diagnoses (ICD-9-CM).



Secondary Outcome Measures:
  • Safety: occurrence of bleeding events leading to hospitalization not specified as primary safety outcomes ("other bleeding") in individuals receiving rivaroxaban, in comparison with those receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]

    A patient will have to meet the following criteria to be considered a case of "other bleeding":

    Admitted to hospital with a bleeding event occurring before hospitalization (i.e. excluding inhospital bleeding events).

    Cases will be identified by hospital discharge diagnoses (ICD-9-CM).


  • Safety: occurrence of non-infective liver disease leading to hospitalization in individuals receiving rivaroxaban in comparison with those receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]

    A patient will have to meet both of the following criteria to be considered a case of non-infective liver disease:

    The patient having been admitted to hospital with acute liver injury. Free of cancer, other liver disease (including infectious hepatitis, chronic liver disease etc.), gallbladder or pancreatic disease and alcoholism.


  • Effectiveness: occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) in individuals receiving rivaroxaban in comparison with those receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]

    A patient will have to meet the following criteria to be considered a case of DVT or PE:

    The patient having been admitted to hospital with a diagnosis of DVT or PE or having a DVT or PE diagnosis documented in the general practitioner database.


  • Effectiveness: occurrence of Ischaemic stroke in individuals receiving rivaroxaban in comparison with those receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]
    A patient will have to meet the following criteria to be considered a case of ischaemic stroke: the patient having been admitted to hospital with a diagnosis of ischaemic stroke.

  • Effectiveness: occurrence acute myocardial infarction (MI) in individuals receiving rivaroxaban in comparison with those receiving current standard of care [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]
    A patient will have to meet the following criteria to be considered a case of MI: the patient having been admitted to hospital with a diagnosis of MI.

  • All-cause mortality as well as cause-specific mortality [ Time Frame: up to 8 years ] [ Designated as safety issue: Yes ]
    Date of death as registered in the different databases (GP, pharmacy, hospital deaths) and confirmed through linkage with the Dutch central bureau of genealogy


Estimated Enrollment: 20000
Study Start Date: February 2012
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Rivaroxoban
Patients who have been prescribed Rivaroxaban for the first time
Drug: Rivaroxoban (Xarelto, Bay59-7939)

The treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE), and prevention of recurrent DVT and PE in adult patients (15 mg rivaroxaban twice daily [bid] for 3 weeks, then 15 mg or 20 mg once daily [od], tablets).

The prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (stroke prevention in atrial fibrillation [SPAF]) with one or more risk factors (20 mg rivaroxaban [od], tablets).

The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery (recommended dose: 10 mg rivaroxaban [od] tablets for 35 days following hip replacement surgery and 14 days following knee replacement surgery).

Co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers (recommended dose 2.5 mg rivaroxaban tablets [bid]).

Standard of care
Patients who have been prescribed standard of care for the first time
Drug: Standard of care
For DVT/PE treatment and SPAF, standard of care is treatment with the most widely used vitamin K antagonist, phenprocoumon, and for the secondary prevention of ACS, standard of care is antiplatelet drug(s) such as low-dose acetylsalicylic acid, clopidogrel, dipyridamole, prasugrel, ticlopidine and ticagrelor.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients aged 2 years and above who have been registered in the PHARMO database for at least 1 year before the index date.
Criteria

Inclusion Criteria:

  • All male and female patients who have been prescribed for the first time either Rivaroxaban or standard of care from the date of market authorization of rivaroxaban to Dec 31, 2017

Exclusion Criteria:

  • Patients who have any record of being dispensed their index drug in the year before index date (i.e. cohort entry), or who qualify for both cohorts on the same day will be excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01947985

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com

Locations
Netherlands
Recruiting
Many Locations, Netherlands
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01947985     History of Changes
Other Study ID Numbers: 16646 
Study First Received: September 11, 2013
Last Updated: April 29, 2016
Health Authority: Netherlands: Healthcare Inspectorate (Inspectie voor de Gezondheidszorg)

Keywords provided by Bayer:
Rivaroxaban
Stroke Prevention in Atrial Fibrillation,
Anticoagulants
Hematologic Agents
Therapeutic Uses
Observational
Venous Thromboembolism
Secondary Prevention of Acute Coronary Syndrome
Intracranial Hemorrhages
Gastrointestinal Hemorrhage

Additional relevant MeSH terms:
Acute Coronary Syndrome
Atrial Fibrillation
Pulmonary Embolism
Venous Thrombosis
Arrhythmias, Cardiac
Cardiovascular Diseases
Embolism
Embolism and Thrombosis
Heart Diseases
Lung Diseases
Myocardial Ischemia
Pathologic Processes
Respiratory Tract Diseases
Thrombosis
Vascular Diseases
Rivaroxaban
Anticoagulants
Antithrombins
Enzyme Inhibitors
Factor Xa Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Serine Proteinase Inhibitors

ClinicalTrials.gov processed this record on May 24, 2016