Arrhythmogenic Potential of Drugs (ARITMO) project

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J01) ANTIBACTERIALS FOR SYSTEMIC USE

  (J02) ANTIMYCOTICS FOR SYSTEMIC USE

  (J04) ANTIMYCOBACTERIALS

  (J05) ANTIVIRALS FOR SYSTEMIC USE

  (P01) ANTIPROTOZOALS

  (N05A) ANTIPSYCHOTICS

  (R06) ANTIHISTAMINES FOR SYSTEMIC USE
• Medical condition to be studied:
  Ventricular arrhythmia

  Sudden cardiac death

Population studied

• Short description of the study population:
  Patients who had:; 1. At least one study drug prescription/dispensing during the study period; 2. At least 12 months of continuous enrolment before initial prescription/dispensing of a study drug. This period is required to characterize the subject in relation to previous occurrence of study outcomes or previous exposure to study drugs. Patients with ventricular arrhythmias registered within the year prior the study entry will be identified and analysed in a specific sub-group analysis; 3. For each drug class, no use of any drug belonging to that class for six months before initial prescription/dispensing. This wash-out period is required to avoid selection of prevalent users and potential depletion of suceptibles
• Age groups:
  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  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)
• Estimated number of subjects:
  27000000

Study design details

• Main study objective:
  The aim of this observational database study is to investigate the pro-arrhitmic risk associated with medications belonging to the following classes: anti-infectives, antihistamines and antipsychotics.
• Outcomes:
  primary objective is to estimate the incidence rates and incidence rate ratios of (a) ventricular arrhythmia (VA) and (b) sudden unexpected death (SUD)/sudden cardiac death (SCD) associated with the most frequently prescribed individual anti-infectives, antihistamines and antipsychotics. - to explore the effect of dose and duration of use and route of administration on the association between study outcomes and drugs of interest,- to identify demographic and clinical predictors for the specific drug-induced arrhythmias- to describe the prescribing pattern of the study drugs in different databases
• Data analysis plan:
  Crude incidence rate together with 95% Confidence Interval (CI) for each study outcome will be separately calculated for each drug class and individual medication dividing the number of events occurring during the exposure to the study drug(s) by the total number of person-years of exposure.Age and gender specific incidence rates will also be assessed in an external reference group from general population in order to estimate the background incidence rate for study ouctomes.Case control studies will be conducted separately within each inception cohort of new users of the study drug classes. By means of conditional logistic regression analyses, odds ratios (ORs) together with 95% CI will be calculated for each individual study drug as compared to corresponding reference category, adjusted for potential confounders. All analyses will first be performed for each database separately and the heterogeneity between databases will be examined.

Documents

Study results

ARITMO_Executive_Summary_08.08.2013