Ventricular TachyarrhythmiaNCT04024865
Domperidone and Risk of Serious Cardiac Events in Postpartum Women
An observational study of Ventricular Tachyarrhythmia and Sudden Cardiac Death, run by Canadian Network for Observational Drug Effect Studies, CNODES at 1 site in Canada.
Trial summary
The purpose of this study is to determine whether the use of domperidone is associated with an increased risk of serious cardiac events among postpartum women in the six months following delivery. Read more about this study
- Who is it for?
- Ages 15 to 55 years, women only
- Conditions the study is for
- Ventricular Tachyarrhythmia, Sudden Cardiac Death, Lactation
- What is being tested?
- Domperidone and No domperidone
- How many people
- 184,929 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2017to 31 Jul 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 55 years
- Women only
- No healthy volunteers
- Child, Adult
Study population: In each jurisdiction, the investigators will assemble a base cohort that includes all women aged between 15 and 55 years old with live births between April 1, 1997 and December 31, 2016 (or the latest available data at each site). Base cohort entry will be defined by the hospital discharge date after delivery. From this base cohort, a study cohort will be formed including all women who received a prescription for domperidone during the six months following delivery and matched women who have a physician visit at the same follow-up time and do not receive domperidone. Study cohort entry will be defined by the prescription date of domperidone for exposed women or the corresponding date of the physician visit for the unexposed women.
Who may be able to join
- Women aged between 15 and 55 years old with live births between April 1, 1997 and December 31, 2016 (or the latest available data at each site)
Who cannot join
- Women with less than 365 days of healthcare coverage prior to the start of pregnancy
- Women with a domperidone prescription in the year prior to or during pregnancy
- Women with a diagnosis of Parkinson's disease or other diseases that cause autonomic dysfunction or use of antiparkinsonian agents anytime before delivery
- Women with a diagnosis of gastroparesis in the year prior to or during pregnancy
- Women with a diagnosis of ventricular tachyarrhythmia in the year prior to or during pregnancy
Trial locations and contacts
1 site in 1 country.
Canada1 site
Lady Davis Institute for Medical Research, Jewish General Hospital
Montreal, Quebec, H3T1E2
About this study
Official title: Use of Domperidone and Risk of Serious Cardiac Events in Postpartum Women
The purpose of this study is to determine whether the use of domperidone is associated with an increased risk of serious cardiac events among postpartum women in the six months following delivery. The hypothesis is that the use of domperidone will be associated with an increased risk of serious cardiac events among postpartum women.
The investigators will carry out separate population-based cohort studies using health care databases in five Canadian provinces. Women with live births will be eligible to enter the cohort. We will identify all women who start domperidone during the six months following delivery and match them to similar women who do not start domperidone, with all included women followed until the occurrence of an adverse cardiac event or for up to six months after delivery. The results from the separate sites will be combined to provide an overall assessment of the risk of serious cardiac events in users of domperidone.
Read the detailed description
The overall objective of this study is to determine whether the use of domperidone is associated with an increased risk of serious cardiac events among postpartum women in the six months following delivery. More specifically, the investigators will assess whether domperidone is associated with the risk of ventricular tachyarrhythmia (VT) and sudden cardiac death (SCD).
A distributed, common-protocol approach will be used to conduct retrospective cohort studies using administrative health care data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario and Saskatchewan). Briefly, the Canadian databases include population-level data on physician billing, diagnoses and procedures from hospital discharge abstracts, and dispensations for prescription drugs. The Ontario data will be restricted to social assistance recipients.
To assess this potential drug safety issue, the investigators will use a prevalent new-user cohort design as described by Suissa et al., 2017. In each jurisdiction, the investigators will first assemble a base cohort that includes all women aged between 15 and 55 years old with live births between April 1, 1997 and December 31, 2016 (or the latest available data at each site). Base cohort entry will be defined by the hospital discharge date after delivery. From this base cohort, a study cohort will be formed including all women who received a prescription for domperidone during the six months following delivery and matched women who have a physician visit at the same follow-up time and do not receive domperidone. Study cohort entry will be defined by the prescription date of domperidone for exposed women or the corresponding date of the physician visit for unexposed women. Women will be followed from the study cohort entry date until an event (defined below) or end of follow up (six months after delivery). Women will be permitted to contribute more than one observation to the study provided that each observation meets all the inclusion criteria.
Exposure to domperidone will be defined as a prescription for domperidone during the six months following delivery. Women not exposed to domperidone will serve as the reference group. Analyses will be conducted using an approach analogous to an intention-to-treat. Unexposed women who are subsequently exposed to domperidone will be censored at the time of the domperidone prescription. The primary outcome will be a composite endpoint of VT or SCD. Secondary outcomes will be the individual endpoints of VT, SCD, and all-cause mortality; separate follow-up durations will be estimated for each outcome.
Using a prevalent new-user design with time-based exposure sets, each user of domperidone will be matched to 10 unexposed women with a physician visit within ±30 days of the first domperidone dispensing of the exposed woman. Matching will be done on propensity score and calendar date of base cohort entry (i.e., hospital discharge from delivery hospitalization). Cox proportional hazards models will be used to estimate site-specific adjusted hazards ratios (HR) and corresponding 95% confidential intervals (CI) for each outcome of interest among postpartum women. Robust sandwich variance estimators will be used to account for potential within-subject clustering. As secondary analyses, the composite endpoint of VT or SCD will be stratified by domperidone dose and duration if feasible. Sensitivity analyses will be performed to assess the robustness of study results. Meta-analyses of the site-specific results will be performed using random-effects models.
In additional analyses, the demographic and clinical characteristics (including perinatal and peripartum characteristics) of women prescribed domperidone in the six months postpartum with those of women not prescribed it during this period will be compared. Furthermore, the impact of Health Canada safety advisories on prescribing patterns will be assessed via interrupted time series analyses.
- Being tested
- Domperidone, No domperidone
- Keywords
- Domperidone, Postpartum, Ventricular Tachyarrhythmia, Sudden Cardiac Death
- Medical subject headings
- Tachycardia, Ventricular, Death, Sudden, Cardiac, Breast Feeding
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DomperidoneDrug
Also called ATC A03FA03
Women who received a prescription for domperidone (ATC A03FA03) during the six months following delivery.
No domperidoneDrug
Women with no prescription for domperidone during the six months following delivery.
| Study group | Role | What they receive |
|---|---|---|
| Treated with domperidone | Women who received a prescription for domperidone during the six months following delivery. Receives: Drug: Domperidone | |
| Unexposed group (reference) | Women with no prescription for domperidone during the six months following delivery. Receives: Drug: No domperidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventricular tachyarrhythmia (VT) or sudden cardiac death (SCD)
VT or SCD will be identified with the following ICD codes:
VT:
ICD-9 codes 427.1, 427.4x; ICD-10 codes I47.0, I47.2, I49.0x
SCD:
ICD-9 codes: V12.53, 427.5, 798.1, 798.2, 798.9; ICD-10 codes: Z86.74, I46.x, R99, R96.0, R96.1, R98
All potential SCD cases will be subjected to a computer algorithm to exclude non-relevant events (such as deaths occurring in hospital or due to non-cardiac pathology). At each site, computerized administrative records of potential SCD cases will be reviewed blinded to the exposure status to verify the accuracy of the algorithm. Finally, all potential cases that are not excluded by the algorithm will be manually reviewed in each site to ensure that all cases meet the event definition.
Measured: Women will be followed from cohort entry until a diagnosis of VT or SCD, death, diagnosis of another indication for domperidone, end of healthcare coverage, or end of the study period (whichever occurs first), or for up to six months after delivery.
Secondary outcomes (1)
All-cause mortality
All-cause mortality, which will include in-hospital and out-of-hospital death, will be defined by a recorded death in any database.
Measured: Women will be followed from cohort entry until death from any cause, diagnosis of another indication for domperidone, end of healthcare coverage, or end of the study period (whichever occurs first), or for up to six months after delivery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2019
- Study start1 Sep 2017
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ventricular TachyarrhythmiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 184,929 participants (actual)
Sponsor and investigators
- Lead sponsor
- Canadian Network for Observational Drug Effect Studies, CNODES
- Sponsor type
- University, hospital or other
- Collaborators
- Drug Safety and Effectiveness Network, Canada, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Kristian B Filion, PhD, Principal investigator, McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04024865
- Sponsor's protocol ID
- Q16-10
- Status last verified
- Jul 2021
- First submitted
- 12 Jul 2019
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Suissa S, Moodie EE, Dell'Aniello S. Prevalent new-user cohort designs for comparative drug effect studies by time-conditional propensity scores. Pharmacoepidemiol Drug Saf. 2017 Apr;26(4):459-468. doi: 10.1002/pds.4107. Epub 2016 Sep 9.
PubMed 27610604Moriello C, Paterson JM, Reynier P, Dahl M, Aibibula W, Fisher A, Gamble JM, Kuo IF, Ronksley PE, Winquist B, Filion KB; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Off-label postpartum use of domperidone in Canada: a multidatabase cohort study. CMAJ Open. 2021 May 14;9(2):E500-E509. doi: 10.9778/cmajo.20200084. Print 2021 Apr-Jun.
PubMed 33990364
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Domperidone and Risk of Serious Cardiac Events in Postpartum Women
- ClinicalTrials.gov ID
- NCT04024865
- Acronym / sponsor ID
- Q16-10
- Keywords
- Domperidone, Postpartum, Ventricular Tachyarrhythmia, Sudden Cardiac Death
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 184,929 participants (actual)
- Lead sponsor
- Canadian Network for Observational Drug Effect Studies, CNODESUniversity, hospital or other
- Collaborators
- Drug Safety and Effectiveness Network, Canada, Canadian Institutes of Health Research (CIHR)
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 18 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the use of domperidone is associated with an increased risk of serious cardiac events among postpartum women in the six months following delivery. The hypothesis is that the use of domperidone will be associated with an increased risk of serious cardiac events among postpartum women.
The investigators will carry out separate population-based cohort studies using health care databases in five Canadian provinces. Women with live births will be eligible to enter the cohort. We will identify all women who start domperidone during the six months following delivery and match them to similar women who do not start domperidone, with all included women followed until the occurrence of an adverse cardiac event or for up to six months after delivery. The results from the separate sites will be combined to provide an overall assessment of the risk of serious cardiac events in users of domperidone.
Detailed description
The overall objective of this study is to determine whether the use of domperidone is associated with an increased risk of serious cardiac events among postpartum women in the six months following delivery. More specifically, the investigators will assess whether domperidone is associated with the risk of ventricular tachyarrhythmia (VT) and sudden cardiac death (SCD).
A distributed, common-protocol approach will be used to conduct retrospective cohort studies using administrative health care data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario and Saskatchewan). Briefly, the Canadian databases include population-level data on physician billing, diagnoses and procedures from hospital discharge abstracts, and dispensations for prescription drugs. The Ontario data will be restricted to social assistance recipients.
To assess this potential drug safety issue, the investigators will use a prevalent new-user cohort design as described by Suissa et al., 2017. In each jurisdiction, the investigators will first assemble a base cohort that includes all women aged between 15 and 55 years old with live births between April 1, 1997 and December 31, 2016 (or the latest available data at each site). Base cohort entry will be defined by the hospital discharge date after delivery. From this base cohort, a study cohort will be formed including all women who received a prescription for domperidone during the six months following delivery and matched women who have a physician visit at the same follow-up time and do not receive domperidone. Study cohort entry will be defined by the prescription date of domperidone for exposed women or the corresponding date of the physician visit for unexposed women. Women will be followed from the study cohort entry date until an event (defined below) or end of follow up (six months after delivery). Women will be permitted to contribute more than one observation to the study provided that each observation meets all the inclusion criteria.
Exposure to domperidone will be defined as a prescription for domperidone during the six months following delivery. Women not exposed to domperidone will serve as the reference group. Analyses will be conducted using an approach analogous to an intention-to-treat. Unexposed women who are subsequently exposed to domperidone will be censored at the time of the domperidone prescription. The primary outcome will be a composite endpoint of VT or SCD. Secondary outcomes will be the individual endpoints of VT, SCD, and all-cause mortality; separate follow-up durations will be estimated for each outcome.
Using a prevalent new-user design with time-based exposure sets, each user of domperidone will be matched to 10 unexposed women with a physician visit within ±30 days of the first domperidone dispensing of the exposed woman. Matching will be done on propensity score and calendar date of base cohort entry (i.e., hospital discharge from delivery hospitalization). Cox proportional hazards models will be used to estimate site-specific adjusted hazards ratios (HR) and corresponding 95% confidential intervals (CI) for each outcome of interest among postpartum women. Robust sandwich variance estimators will be used to account for potential within-subject clustering. As secondary analyses, the composite endpoint of VT or SCD will be stratified by domperidone dose and duration if feasible. Sensitivity analyses will be performed to assess the robustness of study results. Meta-analyses of the site-specific results will be performed using random-effects models.
In additional analyses, the demographic and clinical characteristics (including perinatal and peripartum characteristics) of women prescribed domperidone in the six months postpartum with those of women not prescribed it during this period will be compared. Furthermore, the impact of Health Canada safety advisories on prescribing patterns will be assessed via interrupted time series analyses.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treated with domperidone | – | Drug: DomperidoneWomen who received a prescription for domperidone during the six months following delivery. |
| Unexposed group (reference) | – | Drug: No domperidoneWomen with no prescription for domperidone during the six months following delivery. |
Who may qualify
- Ages
- 15 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- In each jurisdiction, the investigators will assemble a base cohort that includes all women aged between 15 and 55 years old with live births between April 1, 1997 and December 31, 2016 (or the latest available data at each site). Base cohort entry will be defined by the hospital discharge date after delivery. From this base cohort, a study cohort will be formed including all women who received a prescription for domperidone during the six months following delivery and matched women who have a physician visit at the same follow-up time and do not receive domperidone. Study cohort entry will be defined by the prescription date of domperidone for exposed women or the corresponding date of the physician visit for the unexposed women.
Key inclusion criteria (1 listed)
- Women aged between 15 and 55 years old with live births between April 1, 1997 and December 31, 2016 (or the latest available data at each site)
Key exclusion criteria (5 listed)
- Women with less than 365 days of healthcare coverage prior to the start of pregnancy
- Women with a domperidone prescription in the year prior to or during pregnancy
- Women with a diagnosis of Parkinson's disease or other diseases that cause autonomic dysfunction or use of antiparkinsonian agents anytime before delivery
- Women with a diagnosis of gastroparesis in the year prior to or during pregnancy
- Women with a diagnosis of ventricular tachyarrhythmia in the year prior to or during pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DomperidoneAlso: ATC A03FA03Women who received a prescription for domperidone (ATC A03FA03) during the six months following delivery. | Drug | Treated with domperidone |
| No domperidoneWomen with no prescription for domperidone during the six months following delivery. | Drug | Unexposed group (reference) |
Primary outcome
Ventricular tachyarrhythmia (VT) or sudden cardiac death (SCD)
Time frame: Women will be followed from cohort entry until a diagnosis of VT or SCD, death, diagnosis of another indication for domperidone, end of healthcare coverage, or end of the study period (whichever occurs first), or for up to six months after delivery.
VT or SCD will be identified with the following ICD codes: VT: ICD-9 codes 427.1, 427.4x; ICD-10 codes I47.0, I47.2, I49.0x SCD: ICD-9 codes: V12.53, 427.5, 798.1, 798.2, 798.9; ICD-10 codes: Z86.74, I46.x, R99, R96.0, R96.1, R98 All potential SCD cases will be subjected to a computer algorithm to exclude non-relevant events (such as deaths occurring in hospital or due to non-cardiac pathology). At each site, computerized administrative records of potential SCD cases will be reviewed blinded to the exposure status to verify the accuracy of the algorithm. Finally, all potential cases that are not excluded by the algorithm will be manually reviewed in each site to ensure that all cases meet the event definition.
1 secondary outcome
All-cause mortality
Time frame: Women will be followed from cohort entry until death from any cause, diagnosis of another indication for domperidone, end of healthcare coverage, or end of the study period (whichever occurs first), or for up to six months after delivery.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 27610604Suissa S, Moodie EE, Dell'Aniello S. Prevalent new-user cohort designs for comparative drug effect studies by time-conditional propensity scores. Pharmacoepidemiol Drug Saf. 2017 Apr;26(4):459-468. doi: 10.1002/pds.4107. Epub 2016 Sep 9.
- Results publication: PubMed 33990364Moriello C, Paterson JM, Reynier P, Dahl M, Aibibula W, Fisher A, Gamble JM, Kuo IF, Ronksley PE, Winquist B, Filion KB; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Off-label postpartum use of domperidone in Canada: a multidatabase cohort study. CMAJ Open. 2021 May 14;9(2):E500-E509. doi: 10.9778/cmajo.20200084. Print 2021 Apr-Jun.
- This is the organization\'s website describing general functions, other CNODES projects, and investigator profiles.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristian B Filion, PhD principal investigator
McGill University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ventricular Tachyarrhythmia and Sudden Cardiac Death, run by Canadian Network for Observational Drug Effect Studies, CNODES at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventricular tachyarrhythmia (VT) or sudden cardiac death (SCD) (time frame: Women will be followed from cohort entry until a diagnosis of VT or SCD, death, diagnosis of another indication for domperidone, end of healthcare coverage, or end of the study period (whichever occurs first), or for up to six months after delivery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04024865, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.