Domperidone and Risk of Sudden Cardiac Death

NCT02500108 | Completed

• 1 other identifier: Q13-02
• Study Type: observational
• Target: 214,962
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the risk of serious cardiac events, specifically ventricular tachyarrhythmia and sudden cardiac death (VT/SCD), associated with the use of domperidone in a population of patients with Parkinson's disease. The hypothesis for this study is that the risk of VT/SCD will be higher among domperidone users, especially at a higher dose. The investigators will conduct a retrospective population-based cohort study using health care databases in eight jurisdictions in Canada and the UK. The study cohort will be defined by the initiation of a new antiparkinsonian drug or a new diagnosis of Parkinson's disease. The results from the separate sites will be combined by meta-analysis to provide an overall assessment of the risk of VT/SCD in users of domperidone.

Conditions

Parkinson's Disease

Keywords

Domperidone; Ventricular Tachyarrhythmia; Sudden cardiac death; Pharmacotherapy; Adverse events

Outcome Measures

Primary Outcomes (1)

• Ventricular tachyarrhythmia (VT) or sudden cardiac death (SCD)

  VT/SCD will be defined as patients with one of the following diagnostic codes: VT: ICD-9 codes 427.1, 427.4; ICD-10 codes I47.0, I47.2, I49.0. SCD/ cardiac arrest: ICD-9 codes: V12.53, 427.5, 798.1, 798.2, 798.9; ICD-10 codes: Z86.74, I46.0, I46.1, I46.9, R96.0, R96.1, R98. All potential cases will be subjected to a computer algorithm to exclude non-relevant events (such as events due to non-arrhythmic cardiac causes or acute life-threatening non-cardiac causes); all potential cases that are not excluded by the algorithm will be reviewed in each centre to exclude cases that do not meet the inclusion and exclusion criteria.

  Patients will be followed from the date of study cohort entry until the occurrence of VT or SCD, censoring, or for up to 16 years.

Study Arms (2)

Treated with domperidone

Patients who received a new prescription for domperidone (ATC A03FA03) in the year prior to the index date.

Drug: Domperidone

Unexposed (reference) group

Patients with no prescription for domperidone in the year prior to the index date.

Interventions

Domperidone DRUG

Current exposure to domperidone will be defined as a prescription dispensed within 30 days before the index date. Recent exposure to domperidone will be defined as a prescription dispensed between 31 and 90 days before the index date (without a dispensing during the 30 days period preceding index date). Past exposure to domperidone will be defined as a prescription dispensed between 91 and 365 days before the index date (without prescription in the 90 days period prior index date).

Treated with domperidone

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population will consist of all subjects with a diagnosis of Parkinson's disease or a prescription for an antiparkinsonian drug who were registered for provincial medical services coverage or registered in a clinical practice (CPRD) at any time between January 1, 1990 (or 1 year after site-specific data is available, whichever is later) and June 30, 2012.

You may qualify if:

• Patients with a diagnosis of Parkinson's disease or a prescription for an antiparkinsonian drug, with at least 365 days of information in the database prior to cohort entry.

You may not qualify if:

• Age \< 50 on the cohort entry date; or age \< 66 in databases with seniors only
• Missing gender
• Less than 1 year of provincial Medicare enrollment and equivalent enrollment in the CPRD preceding cohort entry
• Patients in a long term care facility
• Diagnosis of PD or dispensing (prescription in CPRD) of an antiparkinsonian drug in the year preceding cohort entry
• Patients with a prescription for an antiparkinsonian drug without a diagnosis of Parkinson's disease but with another indication such as atypical Parkinsonism or secondary Parkinsonism, restless legs syndrome, hyperprolactinemia, or acromegaly in the year before cohort entry
• All patients with a prescription for domperidone in the year before cohort entry
• All patients with a history of ventricular tachyarrhythmia, aborted cardiac arrest, implantation of a cardiac defibrillator, cancer other than non-melanoma skin cancer
• Cohort entry date same as cohort exit date (no follow-up)

Sponsors & Collaborators

• Canadian Network for Observational Drug Effect Studies, CNODES: lead
• Drug Safety and Effectiveness Network, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Lady Davis Institute for Medical Research, Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Related Publications (1)

• Renoux C, Dell'Aniello S, Khairy P, Marras C, Bugden S, Turin TC, Blais L, Tamim H, Evans C, Steele R, Dormuth C, Ernst P; Canadian Network for Observational Drug Effect Studies (CNODES) investigators. Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease. Br J Clin Pharmacol. 2016 Aug;82(2):461-72. doi: 10.1111/bcp.12964. Epub 2016 May 19.

  PMID: 27062307 RESULT

Related Links

• This organization's website describing general functions, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Parkinson Disease; Tachycardia, Ventricular; Death, Sudden, Cardiac

Interventions

Domperidone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Arrest; Death, Sudden; Death

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Christel Renoux, MD, PhD

  Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 16, 2015
• Study Start: May 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

CA (1)