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

Study Overview
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Brief Summary
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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 Warfarin for the first time, the occurrence of intracranial haemorrhage, gastrointestinal and urogenital bleeding, and the occurrence of non-infective liver disease.

Official Title
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A Pharmacoepidemiological Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Pratice in the United Kingdom.

Conditions
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Venous Thrombosis, Pulmonary Embolism, Atrial Fibrillation, Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, Bay59-7939)
* Drug: Warfarin
* Drug: Antiplatelet drugs


Participation Criteria
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Eligibility Criteria
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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 prescribed their index drug prior to the enrolment period or who qualify as members of both cohorts on the same day, will be excluded

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rivaroxaban / Cohort 1<br>Patients who have been prescribed Rivaroxaban for the first time | Drug: Rivaroxaban (Xarelto, Bay59-7939)<br>* 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]).<br>|
| Standard of care / Cohort 2<br>Patients who have been prescribed Standard of care for the first time | Drug: Warfarin<br>* For VTE prevention, DVT/PE treatment and SPAF, standard of care is treatment with the most widely used vitamin K antagonist, warfarin.<br>Drug: Antiplatelet drugs<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Up to 8 years | 
| Characteristics of rivaroxaban use in comparison with standard of care |  | Up to 8 years | 
| Safety: occurrence of intracranial haemorrhage leading to hospitalization among users of rivaroxaban in comparison with individuals receiving current standard of care | Cases of intracranial haemorrhage will be identified in patients referred to a specialist or admitted to hospital that meet the criteria for one of the three following categories: incident cases of intracerebral haemorrhage recorded following or in association with computed tomography, magnetic resonance imaging (MRI) or X-ray angiography, or an appropriate therapeutic procedure. incident cases of subarachnoid haemorrhage recorded following computed tomography, MRI, Xray angiography or lumbar puncture, or an appropriate therapeutic procedure. incident cases of epidural, dural, subdural and arachnoid haemorrhage recorded following computed tomography, MRI, X-ray angiography or lumbar puncture, or an appropriate therapeutic procedure. | Up to 8 years | 
| Safety: occurrence of gastrointestinal bleeding leading to hospitalization among users of rivaroxaban in comparison with individuals receiving current standard of care | 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 the patient having been referred to a specialist or admitted to hospital. | Up to 8 years | 
| Safety: occurrence urogenital bleeding leading to hospitalization | A patient will have to meet both of the following criteria to be considered a case of urogenital bleeding: the specific site of bleeding originating in the urogenital tract. the patient having been referred to a specialist or admitted to hospital. | Up to 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | Up to 8 years | 
| Safety: occurrence of non-infective liver disease leading to hospitalization in individuals receiving rivaroxaban in comparison with those receiving current standard of care. | A patient will have to meet all of the following criteria to be considered a case of non-infective liver disease: an increase of more than three times the upper limit of the normal range in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or a combined increase in ALT, AST or alkaline phosphatase and total bilirubin, provided one of them is twice the upper limit of the respective normal range. the patient having been referred to a specialist or admitted to hospital. free of cancer, other liver disease (including infectious hepatitis, chronic liver disease etc.), gallbladder or pancreatic disease and alcoholism. | Up to 8 years | 
| Effectiveness: occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE) in individuals receiving rivaroxaban in comparison with those receiving current standard of care. | 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 | Up to 8 years | 
| Effectiveness: occurrence of Ischaemic stroke in individuals receiving rivaroxaban in comparison with those receiving current standard of care | 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. | Up to 8 years | 
| Effectiveness: occurrence acute myocardial infarction (MI) in individuals receiving rivaroxaban in comparison with those receiving current standard of care | 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 | Up to 8 years | 
| All-cause mortality as well as cause-specific mortality | For ascertainment of mortality automatic computer searches will be performed, based on: Read Codes Death certification incorporated in The Health Information Network (THIN) Registration status of the patient recorded in THIN | Up to 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rivaroxaban, Stroke Prevention in Atrial Fibrillation, Anticoagulants, Hematologic Agents, Therapeutic Uses, Observational, Venous Thromboembolism, Secondary Prevention of Acute Coronary Syndrome, Intracranial Hemorrhages, Gastrointestinal Hemorrhage