Brivaracetam: a Prospective and Multicentre Post-marketing Observational Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- mean percent change in monthly seizure frequency
Study Overview
Brief Summary
Brivaracetam (BRV) is a new antiepileptic drug approved in March 2016 by Health Canada for the adjunctive treatment of focal epilepsy in adults. While randomized controlled trials represent the gold standard in measuring intervention efficacy, the generalizability of these findings to usual clinical practice remains uncertain.
The primary objective of this study is to evaluate the effectiveness of BRV as an adjunctive treatment in epilepsy. The secondary objective of this study is to evaluate the tolerability of BRV as an adjunctive treatment in epilepsy.
This is a prospective and multicentre post-marketing observational study. All consecutive adult patients (i.e. aged at least 18 years) in whom BRV is introduced in participating medical centres, ambulatory or hospitalized, will be approached to participate in the study. The investigators will exclude individuals with generalized epilepsy as those aged less than 18 years, in order to respect current Health Canada indications. The investigators will exclude individuals cognitively or physically unable to complete the study questionnaires.
The investigators will collect data from participants during three clinical visits with their regular treating physician. These will be the baseline visit, the 3-month visit (three months following the initiation of BRV), and the 6-month visit. At each visit, the investigators will collect data on seizure type(s) and frequency. Study participants will also complete four questionnaires to measure irritability, anxiety, depression, and quality of life.
There will be two primary study outcomes. These are: a) mean percent change in monthly seizure frequency; and b) proportion with at least a 50% decrease in seizure frequency. There will be several secondary study endpoints: a) mean change in irritability [measured using the Brief Irritability Test (BITe)]; b) mean change in generalised anxiety [measured using the Generalized Anxiety Disorder - 7 (GAD-7) scale]; c) mean change in depression [measured using the Neurological Disorders Depression Inventory (NDDI-E) scale]; d) mean change in quality of life [measured using the 7-item Quality of Life Inventory in Epilepsy-10 (QOLIE-10) scale]; e) the proportion of individuals that are seizure free, and f) change in distribution of seizure types (e.g. focal with motor seizures, generalized absence). The investigators will query for all adverse effects the participant may experience.
Detailed Description
Study introduction/rationale:
Brivaracetam (BRV) is a new antiepileptic drug (AED) approved in March 2016 by Health Canada for the adjunctive treatment of focal epilepsy in adults. Three phase III clinical trials (randomized, blinded, and placebo-controlled) have confirmed its efficacy with an acceptable adverse effects profile. While randomized controlled trials represent the gold standard in measuring intervention efficacy, the generalizability of these findings to usual clinical practice remains uncertain. These questions are in part because of certain aspects of the pivotal studies' design. These include: a) participation was limited to individuals with frequent focal seizures (at least eight seizures during an eight-week baseline period), with or without secondary generalization who were already treated with 1 or 2 AEDs; b) individuals aged less than 16 years and greater than 70 years (80 years in one study) were excluded, as well as individuals with cerebral neoplasms, psychogenic non-epileptic seizures, or status epilepticus within the preceding 12 months; d) BRV was introduced at fixed doses without a titration period; and e) the treatment period was limited to 12 The weeks. Inherent to any clinical trial, there remain questions as to what effect local clinical practice and patterns of reimbursement may have on intervention effectiveness (a measure of real-life efficacy that considers issues such as non-compliance). Clinical trials are also at high risk of the Hawthorne effect, where participants modify their behaviour (e.g. increased compliance) due to the knowledge that they are observed.
Canada is one of the first countries where BRV was commercialized. This allows for an important opportunity for investigators to carry out a prospective observational study to establish BRV's effectiveness and tolerability in routine clinical practice.
Primary study objective:
The primary objective of this study is to evaluate the effectiveness of BRV as an adjunctive treatment in epilepsy.
Study Design
- Study Type
- Observational
- Observational Model
- Case Only
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •All consecutive adult patients (i.e. aged at least 18 years) with focal epilepsy in whom BRV was introduced (no more than 48 hours prior to their time of recruitment) at participating medical centres, ambulatory or hospitalized, will be approached to participate in the study.
Exclusion Criteria
- •We will exclude individuals with generalized epilepsy as well as those aged less than 18 years, in order to respect current Health Canada indications. We will exclude individuals cognitively or physically unable to complete the study questionnaires.
Outcomes
Primary Outcomes
mean percent change in monthly seizure frequency
Time Frame: 3 and 6 months
change in frequency of any seizures
proportion with at least a 50% change in seizure frequency
Time Frame: 3 and 6 months
otherwise referred to as the "responder rate"
Secondary Outcomes
- the proportion of individuals that are seizure free(3 and 6 months)
- mean change in irritability(3 and 6 months)
- mean change in generalised anxiety(3 and 6 months)
- mean change in depression(3 and 6 months)
- mean change in quality of life(3 and 6 months)
- change in distribution of seizure types(3 and 6 months)
- adverse effects(3 and 6 months)