Domperidone and the Risk of Serious Adverse Events

NCT07098078 | Completed

• 2 other identifiers: 2025 0906 594 000ICES # 2025 0906 594 000
• Study Type: observational
• Target: 15,000
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess whether initiating domperidone at doses ≥30 mg/day compared to \<30 mg/day in patients with advanced chronic kidney disease (CKD) (estimated glomerular filtration rate \[eGFR\] \<45 mL/min/1.73 m² but not receiving dialysis) is associated with a higher 30-day risk of a composite outcome of all-cause hospitalization or all-cause emergency visits or all-cause mortality.

Conditions

Chronic Kidney Disease (CKD)

Keywords

chronic kidney disease; high-throughput computing; domperidone; adverse events; older adults

Outcome Measures

Primary Outcomes (1)

• Number of participants with a composite outcome of all-cause hospitalization or all-cause emergency visits, or all-cause mortality

  All-cause hospitalization, all-cause emergency visits, and all-cause mortality will be combined into a composite measure. Only the first hospitalization and first emergency department visit occurring after the cohort entry date will be considered.

  Exposed cohort to domperidone (high dose (≥30 mg/d) versus low dose (<30 mg/d)) will enter the cohort between January 1, 2008, and September 30, 2024, and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

Secondary Outcomes (3)

• Number of participants with all-cause hospitalization

  Exposed cohort to domperidone (high dose (≥30 mg/d) versus low dose (<30 mg/d)) will enter the cohort between January 1, 2008, and September 30, 2024, and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

• Number of participants with all-cause emergency department visits

  Exposed cohort to domperidone (high dose (≥30 mg/d) versus low dose (<30 mg/d)) will enter the cohort between January 1, 2008, and September 30, 2024, and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

• Number of participants with all-cause mortality

  Exposed cohort to domperidone (high dose (≥30 mg/d) versus low dose (<30 mg/d)) will enter the cohort between January 1, 2008, and September 30, 2024, and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

Other Outcomes (2)

• 30-day hospital encounter with composite outcome of Atrial Fibrillation/flutter or ventricular arrhythmia or other arrhythmia

  Exposed cohort to domperidone (high dose (≥30 mg/d) versus low dose (<30 mg/d)) will enter the cohort between January 1, 2008, and September 30, 2024, and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

• 30-day hospital encounter with composite outcome of delirium or falls or encephalopathy, or CT scan of the head

  Exposed cohort to domperidone (high dose (≥30 mg/d) versus low dose (<30 mg/d)) will enter the cohort between January 1, 2008, and September 30, 2024, and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

Study Arms (2)

Low dose of domperidone <30 mg/day

Residents of Ontario and Alberta aged 66 years or older with advanced CKD with an eGFR of less than 45 mL/min/1.73m² (excluding individuals undergoing dialysis or those who have received a kidney transplant) who have filled a new oral prescription for domperidone (low dose \<30mg/day) at an outpatient pharmacy under Ontario Drug Benefit (ODB) program from January 1, 2008, to September 30, 2024. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. The accrual period for Alberta will be determined.

Drug: Domperidone (drug)

High dose of domperidone ≥ 30 mg/day

Residents of Ontario and Alberta aged 66 years or older with advanced CKD with an eGFR of less than 45 mL/min/1.73m² (excluding individuals undergoing dialysis or those who have received a kidney transplant) who have filled a new oral prescription for domperidone (high dose ≥ 30 mg/day) at an outpatient pharmacy under Ontario Drug Benefit (ODB) program from January 1, 2008, to September 30, 2024. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. The accrual period for Alberta will be determined.

Drug: Domperidone (drug)

Interventions

Domperidone (drug) DRUG

The primary exposure of interest will be oral domperidone at a dose of 30 mg or more per day, which represents the median dose found in high-throughput computing analyses. For the primary comparison, oral domperidone at doses below 30 mg per day will be chosen to reduce the influence of indication bias.

Also known as: APO-Domperidone, BIO-Domperidone, Domperidone-10, GMD-Domperidone, JAMP-Domperidone, Mar-Domperidone, PMS-Domperidone [DSC], Priva-Domperidone [DSC], PRZ-Domperidone, TARO-Domperidone, TEVA-Domperidone

High dose of domperidone ≥ 30 mg/day; Low dose of domperidone <30 mg/day

Eligibility Criteria

• Age: 66 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Older adults aged 66 years or older with advanced CKD who filled at least one outpatient prescription for oral domperidone between 2008 and 2024 in Ontario, and Alberta

You may qualify if:

• Older adults aged 66 years or older who filled a new oral prescription for domperidone at an outpatient pharmacy under the Ontario Drug Benefit (ODB) program from January 1, 2008, to September 30, 2024. The investigators will exclude individuals undergoing dialysis or those who have received a kidney transplant. The age criterion is set to guarantee that individuals in this population had at least one year of prior prescription drug coverage. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once.

You may not qualify if:

• The investigators will exclude patients with unusual daily doses of less than 10 mg/day or \>40 mg/day for domperidone. The recommended maximum daily dose for domperidone is 10 mg three times daily (30 mg/day). Some patients may require doses up to 4 times daily.
• To ensure that patients are new domperidone users, the investigators will exclude those with any evidence of domperidone use in the 180 days before the index date.
• Patients with more than one eligible domperidone prescription on the index date will be excluded, as this complicates the ability to ascertain the prescribed dose accurately.
• The investigators will exclude patients with a prescription for any other prokinetic drugs and non-oral study drugs in the previous 180 days (including index date) (Note: - Gastrointestinal drugs (Cisapride, Metoclopramide, Domperidone, Prucalopride, Linaclotide)).
• Patients with a history of kidney failure (receipt of maintenance dialysis or a kidney transplant before cohort entry).
• The investigators will exclude patients discharged from a hospital or emergency department within the two days preceding the index date. In Ontario, when patients initiate a domperidone prescription during a hospital admission, their outpatient prescription is typically dispensed on the day they are discharged or the following day.
• Patients with no serum creatinine measurement in the seven days prior to the year before the index date will be excluded. Patients with unstable baseline kidney function (i.e., if the most recent prior serum creatinine test was an inpatient test \[ER or hospitalization\] and if the corresponding eGFR differed from the most recent outpatient test by 10 mL/min/1.73 m2 or more). Previously been demonstrated that outpatient serum creatinine measurements in the province, conducted on a single occasion, indicate stable values.
• The investigators will exclude patients with eGFR ≥45 mL/min/1.73 m² - to restrict to patients with low kidney function only.
• If more than one eligible prescription is available, restrict it to the first. The date of this prescription will be the index date.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

London Health Sciences Centre Research Institute

London, Ontario, Canada

Location

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Related Links

• Government of Canada. Summary Safety Review - DOMPERIDONE - Serious abnormal heart rhythms and sudden death (cardiac arrest)
• Domperidone: Drug information - UpToDate
• Domperidone (Product Monograph)
• CPS \[Internet\]. Ottawa (ON): Canadian Pharmacists Association; c2017 \[updated 2017, November 01\]. Domperidone \[product monograph\]
• ICES. ICES data \[Internet\]

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Domperidone; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Amit Garg

  London Health Sciences Centre Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: August 1, 2025
• Study Start: January 1, 2008
• Primary Completion: September 30, 2024
• Study Completion: October 30, 2024
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)