Simultaneous Administration of Lorazepam and Levetiracetam in nonconvulsive Status Epilepticus, followed by intravenous valproate

ISRCTN	ISRCTN95396292
DOI	https://doi.org/10.1186/ISRCTN95396292
Clinical Trials Information System (CTIS)	2008-001098-13
Protocol serial number	N/A
Sponsor	UZ Leuven (Belgium)
Funders	UZ Leuven (Main funder) (Belgium), UCB Pharma will provide levetiracetam and an EEG (Belgium)

Submission date: 12/03/2008
Registration date: 30/04/2008
Last edited: 19/05/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Wim van Paesschen
Scientific

UZ Leuven
Neurology
49 Herestraat
Leuven
3000
Belgium

Email	Wim.vanpaesschen@uz.kuleuven.ac.be

Study information

Primary study design	Interventional
Study design	Prospective, randomised, placebo-controlled, double-blind pilot trial.
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Simultaneous Administration of Lorazepam and Levetiracetam in nonconvulsive Status Epilepticus, followed by intravenous valproate
Study acronym	SALLISE
Study objectives	Our objectives were to assess: 1. Whether intravenous (IV) levetiracetam could be administered safely in the treatment of non-convulsive status epilepticus 2. Whether it was efficacious in terminating nonconvulsive status epilepticus quickly when administered together with IV lorazepam 3. Whether is was efficacious in preventing relapse within 12 hours after treatment
Ethics approval(s)	Ethics Committee, UZ Leuven (ref: ML3691)
Health condition(s) or problem(s) studied	Nonconvulsive status epilepticus
Intervention	All patients will receive the standard first-line treatment for status epilepticus during EEG recording. Standard treatment: Intravenous (IV) lorazepam 0.05 mg/kg administered over 5 minutes, followed by valproate 30 mg/kg IV administered over 5 minutes. For the Intervention group, levetiracetam (2,500 mg) will also be administered simultaneously with the lorazepam mentioned above. For the Control group, placebo will be administered simultaneously with the lorazepam in the same manner as for the Intervention group. Vital signs, including blood pressure, pulse and respiratory rate will be assessed before and after the lorazepam or lorazepam + levetiracetam administration, and after administration of valproate. In this protocol, we have reduced the dose of lorazepam from the standard 0.1 mg/kg in view of side effects, including hypotension and hypoventilation in around 20% of cases. If status epilepticus was not controlled, other antiepileptic drugs will be given at the discretion of the treating neurologist. There will be no repeat administration of IV levetiracetam after 12 hours.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Lorazepam, Levetiracetam, valproate
Primary outcome measure(s)	Responder rate immediately after IV administration of lorazepam and before administration of valproate, comparing the group that received placebo versus the group that received levetiracetam.
Key secondary outcome measure(s)	1. Responder rate immediately after IV administration of valproate, comparing the group that received placebo versus the group that received levetiracetam 2. Responder rate 12 hours after IV administration of lorazepam and valproate, comparing the group that received placebo versus the group that received levetiracetam 3. Side effects 30 days after treatment 4. Glasgow Outcome Scale 30 days after treatment
Completion date	31/03/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	80
Key inclusion criteria	1. Adult male and female patients 2. Nonconvulsive SE (NCSE), and more specifically, complex partial SE (CPSE) and SE in coma. NCSE is defined as a change in behaviour and/or mental status from baseline associated with electroencephalogram (EEG) changes consistent with SE. We subdivide CPSE into i) CPSE in patients with epilepsy and ii) CPSE de novo. We consider subtle SE as a subgroup of SE in coma. Subtle SE is defined as SE that evolved from convulsive seizures to seizures with minor motor manifestations, such as muscle twitches, tonic eye deviation and nystagmoid eye jerks, and ictal EEG changes.
Key exclusion criteria	1. Postanoxic myoclonus or myoclonic status epilepticus 2. Organic or psychogenic pseudoseizures 3. Coma with the following EEG patterns: 3.1. Periodic lateralised epileptiform discharges (PLEDs) 3.2. Bilateral independent periodic lateralised epileptiform discharges (BiPLEDs) 3.3. Periodic epileptiform discharges (PEDs) 3.4. Generalized periodic epileptiform discharges 3.5. Stimulus-induced rhythmic periodic ictal-like discharges (SIRPIDs) 3.6. Triphasic waves 4. Cases that are doubtful on electroclinical grounds, in whom a diagnosis of SE would only be made a posteriori after a therapeutic trial with anti-epileptic drugs 5. Current treatment with levetiracetam 6. Contraindications for administration of valproic acid (VPA), such as hepatitis, mitochondrial disease, pancreatitis, pregnancy and hepatic porphyria Note: The following are not part of the exclusion criteria: 1. Prior treatment for seizures 2. Renal failure
Date of first enrolment	01/04/2008
Date of final enrolment	31/03/2010

Locations

Countries of recruitment

Belgium

Study participating centre

UZ Leuven

Leuven
3000
Belgium

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results		13/03/2021	19/05/2022	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes