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Trial registered on ANZCTR


Registration number
ACTRN12620000289910
Ethics application status
Approved
Date submitted
15/01/2020
Date registered
4/03/2020
Date last updated
27/10/2022
Date data sharing statement initially provided
4/03/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Case control study of SUDEP (Sudden unexpected death in epilepsy)
Scientific title
Prospective Mutli-centre Case Control Study of SUDEP (Sudden unexpected death in epilepsy), undertaken by the EpiNet Study Group to identify factors that increase or decrease the risk of SUDEP
Secondary ID [1] 300162 0
HRC 19/420
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
epilepsy 315708 0
sudden death 315709 0
Condition category
Condition code
Neurological 313994 313994 0 0
Epilepsy

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We will follow patients with epilepsy, knowing that some of them will die from SUDEP. When this happens, we will identify 3 control subjects from the same cohort as the SUDEP case, matched for age and sex. We will interview a relative / close friend of the Case, and the 3 controls, and review medical notes to gather information about possible risk factors and / or factors that might reduce the risk. We will also interview one proxy control; this will be a relative / close friend of one of the control subjects to match the manner in which we gather information about the SUDEP cases.
Intervention code [1] 316439 0
Not applicable
Comparator / control treatment
The controls will be people with epilepsy from the same cohort as the patients who have died from SUDEP.. A proxy control;will be a relative / close friend of one of the control subjects.
Control group
Active

Outcomes
Primary outcome [1] 322484 0
Health and treatment status, and socioeconomic factors relating to epilepsy as assessed by study-specific questionnaire.
Timepoint [1] 322484 0
At point of SUDEP.
Secondary outcome [1] 378806 0
Living circumstances as assessed by study-specific questionnaire.
Timepoint [1] 378806 0
At point of SUDEP.

Eligibility
Key inclusion criteria
Inclusion criteria for cases and true controls:
1.People with epilepsy. Epilepsy will be defined according to the ILAE 2014 definition, and will therefore potentially include patients who have had only a single seizure, if they meet the other criteria required by this definition. The investigator must have a level of certainty of at least 80% that they actually do have epilepsy.
2.The patient must be a member of a pre-defined cohort. Each centre will define a cohort from which cases and controls will be prospectively identified. The cohort will comprise people with epilepsy who have been seen at the centre since a specific date.
Additional inclusion criteria for cases:
1.Cause of death is definite or probable SUDEP (with or without other co-morbidities), using the modified criteria for diagnosis of SUDEP proposed by Devinsky et al (2018).
2.Date of death is after the start date of the study
3.Death identified to investigator within 12 months of death
Additional inclusion criteria for true controls:
1.Matched to individual case by age (+/- 2 years)
2.Matched to individual case by sex
3. Enrolled in the same cohort as the case, at the time of death of the case.
Inclusion criteria for proxy-controls:
1. Spouse, relative or close friend of a true control who is randomly selected from the triplet of true controls.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who die of SUDEP cannot be included if they were not included in a predetermined cohort before they died.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Case control
Timing
Prospective
Statistical methods / analysis
200 cases and 800 controls, including 200 proxy controls, will detect an odds ratio of 1.7 over a control exposure range of 22-65%, with 80% power and 95% confidence level (2-sided). If the estimated risk of SUDEP is 1/1000 per patients per year, then we will need 200 000 patient-years of follow up. The cohorts we define will be enriched, as they will have a high incidence of patients with drug resistant epilepsy; the risk of SUDEP in this patient group may be as high as 1 in 200; however, we aim to follow a greater number of patients than 50,000 PWE, as we may not hear of all cases of SUDEP in the appropriate time interval.
Data cleaning will be performed prior to analysis. Odds ratios will be calculated using the Mantel-Haenszel method and logistic regression to control for covariates.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/03/2020
Actual
28/01/2020
Date of last participant enrolment
Anticipated
16/03/2024
Actual
Date of last data collection
Anticipated
2/01/2025
Actual
Sample size
Target
1000
Accrual to date
44
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 22213 0
New Zealand
State/province [1] 22213 0
Country [2] 22214 0
United Kingdom
State/province [2] 22214 0
Country [3] 22215 0
Italy
State/province [3] 22215 0
Country [4] 22216 0
United States of America
State/province [4] 22216 0
Country [5] 22225 0
Norway
State/province [5] 22225 0
Country [6] 22226 0
Portugal
State/province [6] 22226 0
Country [7] 22227 0
Hungary
State/province [7] 22227 0
Country [8] 22228 0
Malaysia
State/province [8] 22228 0
Country [9] 22229 0
Ireland
State/province [9] 22229 0
Country [10] 22230 0
Mexico
State/province [10] 22230 0

Funding & Sponsors
Funding source category [1] 304602 0
Government body
Name [1] 304602 0
Health Research Council of New Zealand
Country [1] 304602 0
New Zealand
Primary sponsor type
Other Collaborative groups
Name
EpiNet Study Group
Address
Neurology Department, Auckland City Hosptial, Park Rd, Auckland, New Zealand
Private Bag 92024, New Zealand
Country
New Zealand
Secondary sponsor category [1] 304893 0
Government body
Name [1] 304893 0
Auckland District Health Board
Address [1] 304893 0
Neurology Department, Auckland City Hosptial, Park Rd, Auckland, New Zealand
Private Bag 92024, New Zealand
Country [1] 304893 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305022 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 305022 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 305022 0
New Zealand
Date submitted for ethics approval [1] 305022 0
Approval date [1] 305022 0
19/12/2019
Ethics approval number [1] 305022 0
19/NTA/151

Summary
Brief summary
Sudden unexpected death in people with epilepsy (SUDEP) is an under-appreciated tragedy. It has devastating effects on families, friends and colleagues of those who die, and the causes of SUDEP remain unknown.
We will conduct an international, multicentre, prospective, case-control study of SUDEP, recruiting participants over four years. Each centre will define a cohort from which cases and controls will be prospectively identified. The cohort will comprise people with epilepsy who have been seen at the centre since a specific date (no earlier than 01/01/2015).
Cases will be people with epilepsy from these pre-specified cohorts who have died from definite or probable SUDEP (with or without other co-morbidity), or resuscitated (near) SUDEP if the patient died within 72 hours of the initial collapse.
Controls will be people with epilepsy who will be individually-matched by age (±2 years), sex, centre, and enrolled in the cohort at the time of death of the case (with four controls for each case). For each case, three controls will be randomly selected from all patients in the same cohort who meet the above matching criteria, using a random number generator. A fourth control will be a proxy control, who will be a spouse, relative or close friend nominated by a true control, who is randomly selected from the true-control triplet. Use of the proxy controls will allow any measurement error associated with proxy data to be quantified and corrected for.
The families of cases, the control patients, and the families of controls patients (i.e. proxy controls), will be interviewed over the phone by a research coordinator or an epilepsy fellow, using a structured questionnaire. Data from the interviews will be recorded in the EpiNet database. This will include demographic data, socio-economic factors, epilepsy factors, usual sleeping arrangements, epilepsy treatments, co-morbidities, medications, alcohol, caffeine, and cigarette use, plus the use of seizure monitors, nocturnal supervision, and/or anti-suffocation pillows. For cases, relatives will be asked about the deceased's sleeping arrangements for the night of death or for the night immediately prior to death, and whether this was different from the typical sleep arrangements. Controls will be asked questions relating to their sleep arrangements on a specific nominated night's sleep (chosen randomly to be in the two weeks prior to the interview).
Data neurologists, pathologists, and coroners regarding circumstances around the death, the cause of death, epilepsy and treatment factors will also be recorded if available.
The data will be analysed to identify risk factors for SUDEP. Data cleaning will be performed prior to analysis. Odds ratios will be calculated using the Mantel-Haenszel method and logistic regression to control for covariates.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99002 0
Dr Peter Bergin
Address 99002 0
Neurology Department, Auckland City Hospital, Park Rd, Grafton
Private Bag 92024
Auckland 1142
Country 99002 0
New Zealand
Phone 99002 0
+6493074949
Fax 99002 0
+64 9 307 8912
Email 99002 0
[email protected]
Contact person for public queries
Name 99003 0
Erica Beilharz
Address 99003 0
Neurology Department, Auckland City Hospital, Park Rd, Grafton
Private Bag 92024
Auckland 1142
Country 99003 0
New Zealand
Phone 99003 0
+64 9 307 4949
Fax 99003 0
+64 9 307 8912
Email 99003 0
[email protected]
Contact person for scientific queries
Name 99004 0
Peter Bergin
Address 99004 0
Neurology Department, Auckland City Hospital, Park Rd, Grafton
Private Bag 92024
Auckland 1142
Country 99004 0
New Zealand
Phone 99004 0
+64 9 307 4949
Fax 99004 0
+64 9 307 8912
Email 99004 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data collected during the trial will be shared.
When will data be available (start and end dates)?
The data will be available six months after the study has been completed, and a paper regarding the study has been published. We plan to keep the data indefinitely.
Available to whom?
The data will be available for researchers approved by the EpiNet Study Group. We have already made provisional arrangements to combine the data from our study with that obtained by the North American SUDEP registry
Available for what types of analyses?
The data will be available for meta-analyses looking at SUDEP.
How or where can data be obtained?
The data for this study will be recorded in a special registry within the EpiNet database, an encrypted, password-protected international database established to clarify the optimal management of epilepsy. It is available to accredited researchers and clinicians. The EpiNet Study Group can be contacted via the EpiNet website (http://epinet.co.nz/).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

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