Post-authorisation Safety Study: Risk of Out-of-Hospital Sudden Cardiac Death in Users of Domperidone, Users of Proton Pump Inhibitors, and Users of Metoclopramide

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

  Other
• Non-interventional study design, other:
  Case-crossover

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  DOMPERIDONE

Population studied

• Short description of the study population:
  Patients from a single database in the UK, the CPRD, for the years 2005 through 2011 who were at the risk of sudden cardiac death.
• 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)
• Estimated number of subjects:
  15000

Study design details

• Main study objective:
  The research goal is to assess the risk of out-of-hospital Sudden cardiac death (SCD) associated with current use of domperidone compared with the risk in periods of non-use of domperidone or use of other gastrointestinal medications. Of particular interest is the assessment of risk of SCD in relation to estimated daily dose of domperidone and to age.
• Outcomes:
  The endpoint of the study is SCD that occurs outside a hospital or other institutional setting.
• Data analysis plan:
  The absolute risk of SCD will be estimated as the number of SCD events divided by the person-years of follow-up.Incidence rates of SCD stratified by the following factors (Sex, age group, and diabetes status) will be calculated for current use of domperidone, current use of PPI medications, current use of metoclopramide, and non-use of any of these medications.Incidence rate ratios will be calculated comparing current use of domperidone with current use of PPI medications, current use of metoclopramide, and with non-use time, standardised for age and sex. For domperidone users, incidence rates will also be stratified by dose categories and dose-response trend explored.Multivariable conditional logistic regression will be used to estimate the risk of SCD from current domperidone exposure adjusted by potential confounders. A case-crossover analysis in the cases of SCD will allow further control of confounding

Documents

Study publications

Arana A, Johannes C, Varas C, Rothman KJ, McQuay L, Yang Q. Assessment of daily…

Arana A, Johannes CB, McQuay LJ, Varas-Lorenzo C, Fife D. Risk of Out-of-Hospit…

Varas-Lorenzo C, Arana A, Johannes CB, McQuay LJ, Rothman KJ, Fife D. Improving…