Clinical trial NCT06108102: International Post-Stroke Epilepsy Research Repository
Official title: International Post Stroke Epilepsy Research Repository to Characterize Post-stroke Epilepsy Population and Their Outcomes
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Post Stroke Epilepsy
Post Stroke Seizure
Stroke
Epilepsy
Keywords: Post-stroke epilepsy
Clinical outcomes
Prognosis
Individual patient data
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Monash University
First posted: 2023-10-30
Enrollment: 8000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stroke aged ≥18 years, with ischemic or hemorrhagic stroke, presenting with early or late post-stroke seizures. Patients presenting ≤1 week will be classified as early seizures and \>1 week will be classified as late seizures.

Brief summary: The International Post-Stroke Epilepsy Research Repository (IPSERR): The study aims to collate and categorize data reported by post-stroke epilepsy (PSE) researchers and lodge it within the IPSERR. Using the IPSERR database, we will conduct two individual patient data (IPD) analyses: (1) determine epilepsy, functional, and cognitive outcomes in stroke patients who develop post-stroke seizure and (2) build and validate post-stroke epilepsy prediction model and compare performance against existing models.

Detailed description: The cerebrovascular disease is the most common cause of late-onset epilepsy. PSE is associated with increased morbidity, including cognitive decline, dependence, and poor quality of life, and is a critical determinant factor of stroke prognosis. We recently reported a systematic review and meta-analysis of 71 papers that suggested that post-stroke seizures are associated with more significant mortality and poor functional and cognitive outcomes (PMID:37721736). In this study, we observed disparate methods used by the individual investigators. We also noted variations in study reporting. PI aims to analyze existing individual patient data, including those analyzed in the systematic review, by collaborating with colleagues in the field and developing IPSERR into a resource for future collaborative studies that will tackle anti-epileptogenesis drug trial design.

Design and Rationale:

1. International Post-Stroke Epilepsy Research Repository (IPSERR): The PI convened the International Post-Stroke Epilepsy Research Consortium (IPSERC) with co-convenor Dr. Patrick Kwan, Monash University, Australia. IPSERR was subsequently founded to collect retrospective and prospective PSE data to promote all aspects of PSE research. Participating centers will obtain legal approvals for human subject research as per the requirements of their jurisdiction. The PI (NKM) has IRB approval for IPSERR. A data use agreement (DUA) will be executed to receive data. The PI will invite the authors of all 71 papers in the systematic review to join IPSERC and request them to contribute data to IPSERR. A protocol (including the charter) for the proposed IPD analyses has been accepted for publication and will be available to the collaborators for review.
2. The PI will use the Yale Center for Research Computing (YCRC) resources to manage IPSERR's clinical, radiological, and electrophysiological data.
3. The PI will use Redcap for clinical data management. The Redcap server is housed within the Yale-New Haven Hospital secured data center behind their firewall. The databases are encrypted at rest for HIPAA compliance. Full database backups are made twice daily, seven days a week.
4. Study duration: 2023-2029
5. Rationale: Collaboration is vital for PSE research. This is because approximately 10% of stroke patients develop PSE. Together, investigators can collect a large sample of the PSE patient population and conduct robust analyses to draw meaningful conclusions. The collation of IPD from many different sources involving different interventions and stroke subpopulations will strengthen our ability to provide data for future research on many topics relating to PSE. The availability of high-speed internet has made it easier than ever to work closely with colleagues worldwide and share data. There are many examples of such successful efforts. For example, PI Dr. Mishra closely worked with the SITS-ISTR registry at Karolinska University, Stockholm, and the Virtual Stroke Trials Archive (VISTA) at the University of Glasgow, UK. These two international efforts recorded tPA and stroke trial data, respectively, and provided them for testing several hypotheses. Dr. Mishra subsequently worked at the US FDA, where he was exposed to other large collaborative scientific efforts like MDEpiNET. The PI seeks to capitalize on his experiences, network of colleagues worldwide, and recent technological advancement in data science to build the IPSERR. We anticipate that the IPSERR will bring together large datasets from previously conducted PSE research that would otherwise ordinarily remain dormant. The PI will request data from the authors of papers included in the systematic review (N=71 papers reporting approximately 20000 PSE patient data) and from the IPSERC members. The PI will report IPSERR in the first year and the results of the two research projects anchored on it in the second year. The PI will recognize that not all authors of the previously published literature in our systematic review will have data to share. However, even if 20% of the patient data is obtained from those studies, the PI expects an extensive database of approximately 8000 patients. With this success, the PI expects the IPSERR to continue growing. IPSERR will catalytically advance PSE research because it will provide the PSE research community with an extensive database for hypotheses testing and a framework to anchor future prospective studies.

Eligibility criteria: Inclusion Criteria:

* Studies with minimum dataset of 100 patients
* Studies comprising stroke patients aged ≥18 years, with ischemic or hemorrhagic stroke, presenting early or late PSS with data on patient outcome measures.
* Documented consent or waiver of consent following local Institutional Review Board-approved procedure.
* Studies published on human subjects.
* No restriction based on the date or language of publication, gender, or ethnicity.

Exclusion Criteria:

* Studies of patients with a prior history of seizures before the index stroke,
* Studies that did not report outcome data, or are not able to share IPD.

Primary outcomes:
measure: Mortality (modified Rankin Scale = 6)
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Poor functional outcome (modified Rankin Scale 3-6)
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Seizure frequency
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Seizure severity
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Occurrence or frequency of status epilepticus
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Length of hospital stay
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Cognitive decline assessed on an 11-question Mini-Mental State Examination (MMSE) tool or a 30-point Montreal Cognitive Assessment (MoCA) scale
timeFrame: At 1 year, 2 year, and 5 year follow-up
Secondary outcomes:
measure: Recurrent stroke
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Antiseizure medication discontinuation
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Treatment adverse events
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Depression assessed on 21-item Hamilton Depression Rating Scale (HAM-D)
timeFrame: At 1 year, 2 year, and 5 year follow-up
measure: Anxiety assessed on 14-item Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: At 1 year, 2 year, and 5 year follow-up
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Nishant K Mishra, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mishra NK, Kwan P, Tanaka T, Sunnerhagen KS, Dawson J, Zhao Y, Misra S, Wang S, Sharma VK, Mazumder R, Funaro MC, Ihara M, Nicolo JP, Liebeskind DS, Yasuda CL, Cendes F, Quinn TJ, Ge Z, Scalzo F, Zelano J, Kasner SE; International Post-Stroke Epilepsy Research Consortium (IPSERC); International Post Stroke Epilepsy Research Consortium (IPSERC). Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR). BMJ Open. 2023 Nov 15;13(11):e078684. doi: 10.1136/bmjopen-2023-078684.