Childhood Convulsive Status Epilepticus Management In A Resource Limited Setting

NCT03650270 | Completed Phase 3 DMC

• 1 other identifier: 297/2005
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

Convulsive status epilepticus (CSE) is a potentially devastating condition which can result in significant morbidity and mortality. Studies addressing status epilepticus in children are rare and there is a paucity of large randomised controlled trials in children looking at forms of drug treatment for SE. There is consistency worldwide in guidelines for first line treatment of CSE with benzodiazepines, with slight variations in type and route of administration of agents. Second line therapy usually entails phenobarbital or phenytoin parenterally. Both repeated phenobarbital loading doses and midazolam infusions have been shown to be effective and safe in the management of established convulsive SE, but there are no prospective randomized controlled trials comparing the two in children. Our study has been undertaken to review 2 existing, and routinely used, interventions for children presenting to our center with acute convulsive seizures. In order to permit comparable data to be collected we are randomly allocating these standard interventions prospectively. This is in order to compare the efficacy and safety of two treatment protocols (phenobarbital vs phenytoin and midazolam) both of which as stated are already part of existing standard protocols internationally and in South Africa. Parenteral phenobarbital is a safe, affordable and easy to use drug in the management of status epilepticus especially for poorly resourced communities where undertaking infusions may be unsafe, time consuming or unavailable. We hypothesize that repeated phenobarbital loading is as effective and safe, or more so, than phenytoin followed by midazolam infusion in the management of established and refractory childhood convulsive SE. If proven, then the former would be a viable option for all health care workers with access to intravenous routes (including Day hospitals) where infusions are unsafe, time consuming or unavailable.

Conditions

Pediatric Status Epilepticus

Outcome Measures

Primary Outcomes (1)

• Differences in anticonvulsant efficacy between different second-line anticonvulsant treatment protocols

  Assessing the time taken to reach seizure arrest after second-line agents given

  Up to 24 hours from the time the patient was admitted.

Secondary Outcomes (3)

• Differences in how patients tolerate each of the two second-line anticonvulsant treatment protocols

  Up to 24 hours from the time the patient was admitted.

• Differences in need for pediatric intensive care between the two second-line anticonvulsant protocols

  Up to 24 hours from the time the patient was admitted.

• Differences in admission time between patients who receive on of the two second-line anticonvulsant protocols

  For the full duration the patient is admitted, which on average is up to one full week (seven days).

Study Arms (2)

Phenobarbital

EXPERIMENTAL

If allocated to this arm 'Phenobarbital' (PHB group), the clinician gives an IV bolus of phenobarbital (20mg/kg ). If CSE did not terminate after 5 - 10 minutes, a second dose is given at half the dosage (10mg/kg) and a third dose (10mg/kg) is given if CSE persists 5-10 minutes after that.

Drug: Phenobarbital

Phenytoin / Midazolam infusion

ACTIVE COMPARATOR

In the 'Phenytoin / Midazolam infusion' (PHY/MDZ group), children are given a dose (20mg/kg) of IV phenytoin mixed with 50mL of normal saline solution and administered over 30 minutes . If the child is still in CSE 5-10 minutes after the phenytoin is given, they then start on a midazolam infusion. This includes a loading dose of IV midazolam (0.2mg/kg) followed by an infusion set at 3mg/kg into 50mL 5% dextrose water given at a rate of 1-4 mL/hour (equivalent to 1-4 mcg/kg/min ).

Drug: Phenobarbital

Interventions

Phenobarbital DRUG

Three repeated doses of pareneteral phenobarbital was compared to a single parenteral infusion of phenytoin followed by an infusion of parenteral midazolam

Also known as: Phenytoin, Midazolam

Phenobarbital; Phenytoin / Midazolam infusion

Eligibility Criteria

• Age: 1 Month - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children in convulsive status epilepticus (as defined by Trinka et al 2015)

You may not qualify if:

• Children not in convulsive status epilepticus

Sponsors & Collaborators

• University of Cape Town: lead

Study Sites (1)

Red Cross War Memorial Children's Hospital

Cape Town, Western Cape, 7700, South Africa

Location

Related Publications (1)

• Burman RJ, Ackermann S, Shapson-Coe A, Ndondo A, Buys H, Wilmshurst JM. A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line Management for Pediatric Convulsive Status Epilepticus in a Resource-Limited Setting. Front Neurol. 2019 May 15;10:506. doi: 10.3389/fneur.2019.00506. eCollection 2019.

  PMID: 31156538 DERIVED

MeSH Terms

Interventions

Phenobarbital; Phenytoin; Midazolam

Intervention Hierarchy (Ancestors)

Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydantoins; Imidazolidines; Imidazoles; Azoles; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The specific treatment protocol was blinded to the data analyser
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Paediatric Neurology, Red Cross War Memorial Childrens Hospital

Model Details: random allocation to 2 study protocols

Study Record Dates

• First Submitted: August 17, 2018
• First Posted: August 28, 2018
• Study Start: March 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: August 28, 2018

Record last verified: 2018-08

Locations

ZA (1)