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 identification

• PURI:
  https://redirect.ema.europa.eu/resource/24330
• EU PAS number:
  EUPAS3590
• Study ID:
  24330
• Official title and acronym:
  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
• DARWIN EU® study:
  No
• Study countries:
  United Kingdom
• Study description:
  The overall goal of this research study is to find out whether use of domperidone, a gastrointestinal medication taken for symptoms of nausea and vomiting, may increase the chance of out-of-hospital sudden cardiac death (SCD) compared with the use of two other gastrointestinal medications, the proton pump inhibitor (PPI) medications as a group and metoclopramide, and during periods of non-use of all three types of study medications. Earlier studies have found an increased risk of SCD or a combined outcome of SCD and severe ventricular arrhythmia with current use of domperidone compared with non-use. Evidence from these studies suggested that risk was increased among persons aged older than 60 years and among those receiving a dose of more than 30 mg of domperidone per day orally, but there were not enough exposed individuals for a definitive answer to these questions. The current study will contribute additional information by providing an in-depth analysis of the risk of SCD in relation to domperidone by age and dose. To improve on previous studies it is designed as a nested case control and will include metoclopramide use as a comparator medication in addition to PPI medications, and a case-cross over analysis in which each subject will serve as his/her own control. The study will be performed in the CPRD linkable to Health Episode Statistics data.An important goal of the study is to examine whether higher doses of domperidone are related to higher risk of SCD than lower doses or whether patients using domperidone for longer periods of time are at higher risk. For some patients, the information needed to calculate daily dose of domperidone or length of domperidone use may be missing in the electronic database. For these patients, the researchers plan to conduct a survey of their general practitioners to gather information about dose and duration of exposure.The results of the study will be presented in a study report and in a peer reviewed manuscript.
• Study status:
  Finalised

Research institutions and networks

Institutions

RTI Health Solutions (RTI-HS)

France

Spain

Sweden

United Kingdom

United Kingdom (Northern Ireland)

United States

Study timelines

Date when funding contract was signed

Actual: 24/07/2012

Study start date

Planned: 01/01/2013

Actual: 25/01/2013

Data analysis start date

Planned: 28/01/2013

Actual: 20/02/2013

Date of final study report

Planned: 21/12/2013

Actual: 22/08/2014

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Janssen Research and Development, L.L.C.

Study protocol

Initial protocol

0303209 Final Protocol_V1.1_signed

Updated protocol

0303209 Final Protocol_V1.1_blackout

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable