E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Convulsive Status Epilepticus |
|
E.1.1.1 | Medical condition in easily understood language |
A convulsive seizure which continues for a prolonged period (longer than five minutes), or when convulsive seizures occur one after the other with no recovery between. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057955 |
E.1.2 | Term | Convulsive status epilepticus |
E.1.2 | System Organ Class | 100000004852 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To determine whether intravenous phenytoin or intravenous levetiracetam is the more efficacious second-line anticonvulsant for the emergency management of convulsive status epilepticus (CSE) in children. 2. To determine if intravenous levetiracetam is associated with fewer adverse effects than intravenous phenytoin
|
|
E.2.2 | Secondary objectives of the trial |
1. Need for further anticonvulsant(s) to manage the seizure after the initial agent. 2. Need for rapid sequence induction (medical procedure involving giving general anesthesia and then intubation of the trachea) with thiopentone or another agent (e.g. propofol). 3. Need to be admitted to critical care. 4. Serious adverse reactions including death, airway complications, and cardiovascular instability (cardiac arrest, arrhythmia and hypotension requiring intervention), extravasation injury (‘purple-glove syndrome’), extreme agitation.
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The Consent study will involve parents and EcLiPSE recruiters to explore approaches to recruitment and deferred consent. Led by Dr Kerry Woolfall, the Consent study will examine: how information about the trial and deferred consent is exchanged during recruitment discussions; views on deferred consent; and the impact of an un-blinded trial design and potential treatment risks upon acceptability of deferred consent. The aim will be to identify recruitment and consent issues and potential solutions to inform EcLiPSE recruiter training materials. |
|
E.3 | Principal inclusion criteria |
1. Males and females aged 6 months to 18 years (<18th birthday). 2. Presenting seizure is generalised tonic-clonic, generalised clonic or focal clonic status epilepticus that requires second-line treatment to terminate the seizure. 3. First-line treatment administered according to APLS guidelines or the child’s personalised rescue care plan in order to try and terminate the presenting seizure.
Eligibility Notes
• APLS guidelines: Guidelines classify two doses of benzodiazepines as first-line treatment. If patients are given more than two doses of benzodiazepines then they are still eligible.
• Personalised rescue care plan: Patients whose personalised rescue care plan includes rectal paraldehyde as the first-line treatment are still eligible.
• Maintenance anti-epileptic medication: Patients receiving oral phenytoin or levetiracetam as part of their regular oral anti-epileptic drug regime are still eligible for this trial.
|
|
E.4 | Principal exclusion criteria |
1. Absence, myoclonic or non-convulsive status epilepticus, or infantile spasms. 2. Known or suspected pregnancy. 3. Known contra-indication or allergy to levetiracetam or phenytoin. This includes where the child’s personalised rescue care plan states that the child never responds to, or has previously experienced a severe adverse reaction to, phenytoin, levetiracetam, or both. 4. Known renal failure (patients on peritoneal or haemodialysis or with renal function <50% expected for age) 5. Previous administration of a second-line antiepileptic drug prior to arrival in the emergency department. 6. Known to have previously been treated as part of EcLiPSE. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to cessation of all visible signs of convulsive seizure activity.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured from the point of randomisation until 24 hours after second-line treatment infusion has started. |
|
E.5.2 | Secondary end point(s) |
1. Need for further anticonvulsant(s) to manage the seizure after the initial agent. 2. Need for rapid sequence induction (RSI) with thiopentone or another agent (e.g. propofol) due to ongoing CSE. 3. Need to be admitted to critical care. 4. Serious adverse reactions including death, airway complications, and cardiovascular instability (cardiac arrest, arrhythmia and hypotension requiring intervention), extravasation injury (‘purple-glove syndrome’), extreme agitation.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be recorded and reported from the point of randomisation until 24 hours after second-line treatment infusion has started. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 30 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial is defined to be the date of database lock. This is the date on which data modification privileges are withdrawn from the trial database. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 31 |