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

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

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.

Study Overview

• Status: Completed
• Conditions: Venous Thrombosis; Atrial Fibrillation; Acute Coronary Syndrome; Pulmonary Embolism
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, Bay59-7939); Drug: Warfarin; Drug: Antiplatelet drugs

• Study Type: Observational
• Enrollment (Actual): 50299

Contacts and Locations

Study Locations

• United Kingdom
  • Multiple Locations, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients aged 2 years and above who have been enrolled with a primary care physician for at least 1 year and had their first prescription recorded in the THIN database at least 1 year ago

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rivaroxaban / Cohort 1; Patients who have been prescribed Rivaroxaban for the first time	Drug: Rivaroxaban (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 / Cohort 2; Patients who have been prescribed Standard of care for the first time	Drug: Warfarin; For VTE prevention, DVT/PE treatment and SPAF, standard of care is treatment with the most widely used vitamin K antagonist, warfarin.; Drug: Antiplatelet drugs; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 22, 2011
• Primary Completion (ACTUAL): September 30, 2020
• Study Completion (ACTUAL): September 30, 2020

Study Registration Dates

• First Submitted: September 11, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (ESTIMATE): September 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Rivaroxaban; Observational; Venous Thromboembolism; Anticoagulants; Therapeutic Uses; Intracranial Hemorrhages; Hematologic Agents; Gastrointestinal Hemorrhage; Stroke Prevention in Atrial Fibrillation; Secondary Prevention of Acute Coronary Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Arrhythmias, Cardiac; Embolism; Atrial Fibrillation; Thrombosis; Venous Thrombosis; Acute Coronary Syndrome; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Warfarin; Platelet Aggregation Inhibitors
• Other Study ID Numbers: 16647; EUPAS11299 (REGISTRY: ENCEPP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No