Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Practice (Germany)

A Pharmacoepidemiological Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Pratice in Germany

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 Phenprocoumon 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: Standard of care

• Study Type: Observational
• Enrollment (Actual): 665533

Contacts and Locations

Study Locations

• Germany
  • Multiple Locations, Germany

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 in German Pharmacoepidemiological Research Database (GePaRD) for at least one year.

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 dispensed their index drug in the year before index date (i.e. cohort entry), or who qualify for both cohorts on the same day

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rivaroxaban; Patients who have been prescribed Rivaroxaban for the first time	Drug: Rivaroxaban (Xarelto, Bay59-7939); The treatment of DVT or 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.

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	Age and sex distribution 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 Comorbidity based on inpatient and outpatient diagnoses Renal disease based on in- and outpatient diagnoses Healthcare utilization (e.g. number of hospital admissions).	up to 8 years
Characteristics of rivaroxaban use in comparison with standard of care	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)	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 hospitalized patients with a discharge diagnosis of intracranial haemorrhage 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	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: A hospital admission with a discharge diagnosis of gastrointestinal bleeding, i.e. a bleeding riginating 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.	up to 8 years
Safety: occurrence urogenital 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 urogenital bleeding: A hospital admission with a discharge diagnosis of urogenital bleeding.	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": A hospital admission with a discharge diagnosis of "other bleeding"	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: A hospital admission with a discharge diagnosis of acute liver injury. No diagnosis of cancer, other liver disease (including infectious hepatitis, chronic liver disease etc.), gallbladder or pancreatic disease, or 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: A hospital admission with a discharge diagnosis of DVT or PE, or an ambulatory diagnosis of DVT with a dispensation of another antithrombotic agent	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: A hospital admission with a main discharge 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 all of the following criteria to be considered a case of acute myocardial infarction: A hospital admission with a main discharge diagnosis of acute MI	up to 8 years
All-cause mortality as well as cause-specific mortality	Deaths can be identified from core data and hospital data	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): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 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
• Other Study ID Numbers: 16159; XA1201 (OTHER: Company internal); EUPAS11145 (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