Status: Finalised
First registered on:
28/02/2013
Last updated on:
05/06/2018
1. Study identification
EU PAS Register NumberEUPAS3590
Official titlePost-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 title acronym
Study typeObservational study
Brief description of the studyThe 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.
Was this study requested by a regulator?Yes: Belgium
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsRTI-HS
Department/Research groupPharmacoepidemiology & Risk Management
Organisation/affiliationRTI Health Solutions
Details of (Primary) lead investigator
Title Dr
Last name Arana
First name Alejandro
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed24/07/2012
Start date of data collection01/01/201325/01/2013
Start date of data analysis28/01/201320/02/2013
Date of interim report, if expected
Date of final study report21/12/201322/08/2014
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesJanssen Research and Development, L.L.C.100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Arana
First name Alejandro
Address line 1Trav. Gracia, 56, Atico 1
Address line 2
Address line 3
CityBarcelona
Postcode08006
CountrySpain
Phone number (incl. country code)34933622805
Alternative phone number
Fax number (incl. country code)34934142610
Public Enquiries
Title Dr
Last name Arana
First name Alejandro
Address line 1Trav. Gracia, 56, Atico 1
Address line 2
Address line 3
CityBarcelona
Postcode08006
CountrySpain
Phone number (incl. country code)34933622805
Alternative phone number
Fax number (incl. country code)34934142610
6. Study drug(s) information
Single-Constituent (Substance INN)DOMPERIDONE
7. Medical conditions to be studied
Medical condition(s)No
8. Population under study
Age
Children (2 - 11 years)
Adolescents (12 - 17 years)
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects15000
Additional information
Preliminary calculations using CPRD data indicated approximately 160,000 persons with at least one prescription for domperidone from January 1, 2005, through the end of January 2012. Using the percentage of the exposure cohort who experienced SCD from the Saskatchewan study yields an estimate of 3,000 cases.
We will use a 1:4 matching ratio, leading to 3000 cases and 12000 controls.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Routine primary care electronic patient registry
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
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.
Are there primary outcomes?Yes
The endpoint of the study is SCD that occurs outside a hospital or other institutional setting.
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
Case-control study
Case-crossover
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
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
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
Arana A, Johannes C, Varas C, Rothman KJ, McQuay L, Yang Q. Assessment of daily dose of domperidone in the Clinical Practice Research Datalink (CPRD) using multiple information sources. Pharmacoepidemiol Drug Saf. 2014;23(S1):329.
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documents
DescriptionDocumentLatest version
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Submitted
