Rivaroxaban real world effectiveness in patients with atrial fibrillation (GUARDIAN)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Evaluation of patient-reported outcomes

  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  This is an international, non-interventional, observational, prospective, multicentre study evaluating the effectiveness and safety of Krka’s rivaroxaban in patients with AF according to the investigator’s consideration and in compliance with indications stated in SmPC of Krka’s rivaroxaban. Only patients, who would be otherwise also treated with Krka’s rivaroxaban in local regular clinical practice, will be enrolled in this non-interventional study. The decision to prescribe Krka’s rivaroxaban is at the sole discretion of the treating investigator, including dose and duration of Krka’s rivaroxaban therapy.

Study drug and medical condition

• Medicinal product name, other:
  Xerdoxo®
• Study drug International non-proprietary name (INN) or common name:
  RIVAROXABAN
• Anatomical Therapeutic Chemical (ATC) code:
  (B01AF01) rivaroxaban

  rivaroxaban
• Medical condition to be studied:
  Atrial fibrillation

Population studied

• Short description of the study population:
  Patients with diagnosed non-valvular atrial fibrillation (NVAF) who were indicated for treatment with Krka’s rivaroxaban according to the valid SmPC. The patients could have been either naïve (patients who had never taken anticoagulants before) or patients that were already treated with anticoagulants (with exception of rivaroxaban). In the study were included patients who agreed with informed consent form and consent for statistical evaluation of personal data. Only patients who would also otherwise be treated with Krka’s rivaroxaban in local regular clinical practice were enrolled in the study.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Study design details

• Study design:
  Observational, prospective, international, multicentre, non-interventional study. Only patients, who would be otherwise also treated with Krka’s rivaroxaban in line with local regular clinical practice were included in the study. Observation of patients lasted 12±1 month, divided in 4 data captures.
• Main study objective:
  Provide therapeutic data about effectiveness of Krka’s rivaroxaban across the broad range of patient risk profiles in routine clinical practice and to provide overview of the outcomes associated with therapy and factors influencing its use in the management of stroke prophylaxis in AF patients.
• Setting:
  Routine clinical practice
• Outcomes:
  Primary outcomes:; • Assessing the incidence of major bleeding events in the observed study period.; • Assessing the incidence of stroke and/or embolism mortality in the observed study period.; • Assessing the incidence of treatment-emergent adverse reactions in the observed study period.; Secondary outcomes: Includes 18 additional items. At the baseline this includes the assessment of the patient profiles, risk factors (sex, age, BMI, smoking habits, alcohol consumption), proportions of newly diagnosed patients, proportion of patients with comorbidities, evaluation of CHA2DS2-VASc score, evaluation of HAS-BLED score, proportion of patients previously treated with anticoagulants (except rivaroxaban) and proportion of treatment naïve patients. Secondary outcomes at each data capture include the assessment of incidence of symptomatic thromboembolic events (stroke, TIA and systemic embolism or myocardial infarction), the incidence of major bleeding events (fatal bleeding, symptomatic bleeding in a critical area or organ, or a bleeding caused by a fall of haemoglobin level of 1.24 mmol/l (20g/L) or more, or need for transfusion of 2 or more units of packed red blood cells or whole blood), the incidence of non-major bleeding events (any bleeding event that does not meet the criteria for major bleeding event), proportion of patients who need additional treatment of AF besides rivaroxaban, incidence of stroke and/or embolism mortality, incidence of treatment-emergent adverse reactions, evaluation of patient’s satisfaction to Krka’s rivaroxaban therapy in comparison to previous anticoagulant therapy, patient’s satisfaction with dosing regimen of Krka’s rivaroxaban patient’s and investigator’s general satisfaction to Krka’s rivaroxaban therapy, evaluation of reasons for discontinuation of treatment and the incidence of all-cause mortality marked as either vascular or non-vascular.
• Data analysis plan:
  The study characteristics of the protocol were entered into electronic data capture system - the eCRF application. All data and clinical information were collected in accordance with the country specific privacy laws, Helsinki declaration, protocol and regular clinical practice. Corrections made in eCRF by the investigator were captured in audit trail log. In case of missing, misleading or incomplete data during the study conductance, the monitor raised queries. These queries were forwarded to the investigator for clarification. Only the investigator or authorized study personnel were permitted to make data changes or corrections. Summary statistics consists of the number of patients/observations, frequencies and corresponding percentages for categorical variables, and of the number of patients/observations, mean, median, standard deviation, minimum and maximum, first and third quartile for numeric variables. Some variables (numeric discrete variables with few possible values) are summarized both as categorical variables and as numeric variables. For inferential assessment of proportions, the two-sided “equal-tails” Clopper-Pearson exact 95% - confidence interval will be employed. For the assessment of means and mean differences, the standard 95%-confidence interval for the mean (with unknown variance) based on the limiting distribution of the standardized sample mean will be employed.
• Summary results:
  Part of separate document “Summary of final report”.