A pharmacoepidemiological study of Rivaroxaban use and potential adverse outcomes in routine clinical pratice in Germany

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  XARELTO
• Study drug International non-proprietary name (INN) or common name:
  RIVAROXABAN
• Anatomical Therapeutic Chemical (ATC) code:
  (B01A) ANTITHROMBOTIC AGENTS

  ANTITHROMBOTIC AGENTS
• Medical condition to be studied:
  Venous thrombosis

  Pulmonary embolism

  Atrial fibrillation

  Acute coronary syndrome

Population studied

• Short description of the study population:
  All patients aged 2 years and above who have been enrolled in The German Pharmcoepidemiological Research Database (GePaRD) for at least 1 year. Cohorts of first-time users of either rivaroxaban or comparators will be identified using the date of first dispensation of the respective drug (the index drug) as the index date. ; A patient will be considered eligible to enter a study cohort as a first-time user of rivaroxaban or a first-time user of “standard of care” when he or she has a first prescription of the drug dispensed during the enrolment period. In Germany, for VTE prevention, 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. Many patients with ACS have a history of ischaemic heart disease for which platelet inhibition is standard treatment, and thus exclusion of patients with prior use of platelet inhibitors risks excluding a majority of typical ACS patients. Therefore, those who have been using one or more platelet inhibitors will remain eligible to enter the study. ; 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. If a patient qualifies as first-time user of both rivaroxaban and “standard of care” comparison drug during the enrolment period, she/he will be assigned to the cohort of drug first prescribed during the enrolment period, with the date of this prescription being the index date. Many patients with ACS have a history of ischaemic heart disease for which platelet inhibition is standard treatment, and thus exclusion of patients with prior use of platelet inhibitors risks excluding a majority of typical ACS patients. Therefore, those who have been using one or more plate
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with venous thrombosis, pulmonary embolism, atrial fibrillation, acute coronary syndrome
• Estimated number of subjects:
  200000

Study design details

• Main study objective:
  To assess patterns of drug utilization and to quantify outcomes related to safety and effectiveness in new users of rivaroxaban compared with new users of standard of care in routine clinical practice in Germany.
• Outcomes:
  1. 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 2. Characteristics of rivaroxaban use in comparison with standard of care (NOTE: please refer to https://clinicaltrials.gov/ for further primary outcomes), 1. 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. (NOTE: please refer to https://clinicaltrials.gov/ for further secondary outcomes)
• Data analysis plan:
  For descriptive purposes, annualized crude incidence rates of the specified outcome events will be calculated, accompanied by 95% confidence intervals.