Clinical trial NCT01815125: Ondansetron for Pediatric Mild Traumatic Brain Injury
Official title: Ondansetron for Pediatric Mild Traumatic Brain Injury; a Pilot Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Traumatic Brain Injury
Brain Concussion
Keywords: Mild traumatic brain injury
Brain concussion
Post-concussion syndrome
Emergency department
Ondansetron
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2013-03-20
Enrollment: 16
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Most patients suffering from mild Traumatic Brain Injury (mTBI) present persistent symptoms at one week post injury. A systematic review showed a paucity of studies for short term outcomes following mTBI. Among potential treatments for mTBI, ondansetron has shown promising results based on clinical experience and a single retrospective study. Objectives: The primary objective of this pilot study is to determine the feasibility of a randomized controlled trial evaluating the effect of ondansetron to decrease post concussion symptoms at one week following mTBI in children. More specifically, this pilot study will evaluate the proportion of participants who complete assessment at one week following intervention. Method: This will be a randomized, double blinded, controlled trial performed among children aged between 8 and 17 years old who sustained a mTBI in the previous 24 hours. Participants visiting the emergency department will be randomized to receive one dose of either ondansetron or placebo. The primary outcome of interest is defined as an increase from pre-concussion baseline of at least 3 symptoms from the Post Concussion Symptom Inventory (PCSI) one week following trauma. Secondary outcomes will include time to full recovery, mean PCSI score, and outcomes at one month following head trauma. The primary analysis will compare the proportion of participants with persistence of symptoms at one week in both groups. The full study sample size was calculated to have 90% power to detect a decrease in the proportion of persistence of symptoms from 50% to 30% with an alpha value of 0.05. Approximately 126 patients will therefore be recruited in each arm. The investigators plan to recruit 30 participants (10% of the final population) for the pilot study. Expected results: This pilot study should confirm the feasibility of the randomized controlled trial by showing that 90% of the recruited participants provide data on the primary outcome at one week following intervention. On the long term, the investigator expect that ondansetron will decrease the proportion of patients sustaining persistent symptoms of concussion from 50% to lower than 30%.


Eligibility criteria: Inclusion Criteria:

1. Children aged between 8 and 17 years old. This will be limited to this small spectrum of age to insure better homogeneity in the evaluation of the participants and streamlining of outcome measures. Also, this is the age group for which our measurement tool has been validated.
2. Occurrence of a mTBI as defined by the presence of a head trauma, a Glasgow coma scale of 13 to 15 and at least one of the three following criteria4 :

   * Any period of loss of consciousness.
   * Any loss of memory for events immediately before or after the accident.
   * Any alteration in mental state at the time of the accident (eg, feeling dazed, disoriented).

   And the absence of the following criteria:
   * Post-traumatic amnesia greater than 24 hours.
   * Glasgow Coma Scale \< 13, 30 minutes post accident.
3. The trauma occurred in the preceding 24 hours.

Exclusion Criteria:

* 1. Inability to obtain a proper written informed consent (language barrier, absence of a parental authority, developmental delay, intoxication, patient too confuse to consent according to the treating physician).

  2. Known allergic reaction or intolerance to ondansetron. 3. Known rhythm or cardiac problem, or history of sudden death in the proximal family 4. Patients who are taking a medication which could increase the QT interval. 5. Patients who received ondansetron in the previous 24 hours 6. Any abnormality on radiological studies, including any bleeding in the brain or skull fracture.

  7. Multi-system injuries with treatment requiring admission to hospital or procedural sedation in the ED.

Primary outcomes:
measure: Persistence of post concussive symptoms
timeFrame: 1 week post intervention
Secondary outcomes:
measure: Mean number of PCSI symptoms
timeFrame: one week and month following intervention
measure: Mean number of school days missed
timeFrame: one month following intervention
measure: Number of days of sport activity restriction
timeFrame: 1 month following intervention
measure: Time before full recovery
timeFrame: One month following intervention
measure: Healthcare utilization
timeFrame: One month following intervention
measure: Side effects
timeFrame: one week and month following intervention
Other outcomes:
measure: Proportion of participants who complete the assessment at one week following intervention
timeFrame: One week following intervention
measure: Proportion of eligible children who were not included
timeFrame: At baseline
measure: Compliance with study medication
timeFrame: One week following intervention
Locations:
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: CHU Sainte-JUstine, University of Montreal
name: Jocelyn Gravel, MD
role: PRINCIPAL_INVESTIGATOR
References: