An Observational Study to Assess the Risk of Out-of-Hospital Sudden Cardiac Death in Users of Domperidone, Users of Proton Pump Inhibitors, and Users of Metoclopramide

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

The purpose of this observational study is to assess the risk of out-of-hospital Sudden Cardiac (heart) Death (SCD) associated with current use of domperidone compared to current use of a Proton Pump Inhibitor (PPI), current use of metoclopramide, or non-use of any of these medications.

Study Overview

• Status: Completed
• Conditions: Death, Sudden, Cardiac
• Intervention / Treatment: Drug: No intervention

Detailed Description

This is a population-based, retrospective (a study in which the exposures and outcomes occurred before the study began), and nested case-control study (a study in which the patients with the study outcome [cases] and comparison patients without that outcome [controls] are observed to assess their exposure to the medication being studied [domperidone, PPI's and metoclopramide]). The data will come from the United Kingdom's Clinical Practice Research Datalink. The study will estimate the rate of SCD during periods of exposure to each of the study medications, and during periods of exposure to none of them; and the ratios of these rates. It will also use a "case-crossover" analysis (in which each case serves as his/her own control) to re-estimate these rate ratios in a manner that takes account of personal characteristics such as obesity or smoking that may affect the study findings and are incompletely recorded in the database.

• Study Type: Observational
• Enrollment (Actual): 15000

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

Patients with exposure to domperidone, proton pump inhibitor, and metoclopramide

Description

Inclusion criteria:

- Patients registered in English practices whose data are linkable to Hospital Episode Statistics (HES) and Office for National Statistics, UK (ONS). Patients are required to have at least 1 year in the Clinical Practice Research Datalink before they can enter the study

Exclusion criteria:

• Patients with a diagnosis of cancer other than non-melanoma skin cancer
• Patients from practices not linkable to HES and ONS data
• Patient time corresponding to the period between hospital admission date and 30 days after discharge date

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Domperidone/ a proton pump inhibitor/metoclopramide users; Study patients had at least one prescription for domperidone, a proton pump inhibitor, or metoclopramide. Proton pump inhibitors observed in this study are: omeprazole, lansoprazole, esomeprazole, rabeprazole, and pantoprazole.	Drug: No intervention; This is an observational and a retrospective study of existing data, so there will be no interventions. The exposure groups will be domperidone, proton pump inhibitors (omeprazole, lansoprazole, esomeprazole, rabeprazole, and pantoprazole), and metoclopramide.; Other Names: Motilium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of out-of-hospital sudden cardiac death (SCD) associated with the exposure to domperidone, proton pump inhibitor, metoclopramide, and none of these medications	This will be evaluated for the number of study participants (who had SCD) exposed to domperidone, proton pump inhibitor, metoclopramide, and none of these medications. SCD is defined as a natural death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia (irregular heartbeat).	7 years
Number of out-of-hospital Sudden Cardiac Death (SCD) in relation to domperidone exposure period and domperidone non-exposure period	This will be evaluated for the number of study participants who had SCD in relation to domperidone exposure period and domperidone non-exposure period. SCD is defined as a natural death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia (irregular heartbeat). This will be analyzed by case-crossover method (self-matching design) which will be adjusted for personal characteristics that vary little over time in each individual. eg, for obesity.	7 years
Number of out-of-hospital Sudden Cardiac Deaths (SCD) in relation to Proton Pump Inhibitor (PPI) exposure period and PPI non-exposure period	This will be evaluated for the number of study participants who had SCD in relation to PPI exposure period and PPI non-exposure period. SCD is defined as a natural death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia (irregular heartbeat). This will be analyzed by case-crossover method (self-matching design) which will be adjusted for personal characteristics that vary little over time in each individual. eg, for obesity.	7 years
Number of out-of-hospital Sudden Cardiac Deaths (SCD) in relation to metoclopramide exposure period and metoclopramide non-exposure period	This will be evaluated for the number of study participants who had SCD in relation to metoclopramide exposure period and metoclopramide non-exposure period. SCD is defined as a natural death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia (irregular heartbeat). This will be analyzed by case-crossover method (self-matching design) which will be adjusted for personal characteristics that vary little over time in each individual. eg, for obesity.	7 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: July 22, 2013
• First Posted (ESTIMATE): July 25, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): May 19, 2015
• Last Update Submitted That Met QC Criteria: May 18, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Observational Study; Domperidone; Metoclopramide; Proton Pump Inhibitors (PPI); Death, Sudden, Cardiac; Risk of Sudden Cardiac Death
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Arrest; Death; Death, Sudden, Cardiac; Death, Sudden; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine Antagonists; Domperidone
• Other Study ID Numbers: CR102051; RRA-7880 (OTHER: Janssen Research & Development, LLC); Epi 316 (OTHER: Janssen Research & Development, LLC)