Ondansetron for Pediatric Mild Traumatic Brain Injury

Ondansetron for Pediatric Mild Traumatic Brain Injury; a Pilot Randomized Controlled Trial.

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%.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Brain Concussion
• Intervention / Treatment: Drug: Ondansetron; Drug: PLacebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T1C5
      • CHU Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ondansetron; The intervention of interest will be the administration of one dose of oral ondansetron in the emergency department. The dosage will be 8 mg.	Drug: Ondansetron; The intervention of interest will be the administration of one dose of oral ondansetron in the emergency department. The dosage will be 8 mg.; Other Names: Zofran
PLACEBO_COMPARATOR: Placebo; The control group will receive a similar looking/ tasting pill of placebo.	Drug: PLacebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of post concussive symptoms	Persistence of post concussive symptoms will be defined by an increase from pre-concussion baseline of at least 3 symptoms of the Post Concussion Symptom Inventory (PCSI). The PCSI is a self-report tool evaluating the presence of 25 symptoms (on a 3-point likert scale) for children 8-12 and 26 symptoms on a (7-point likert scale) for children 13-17 years. An increase of two points or more from pre-injury in any symptom is considered clinically significant.	1 week post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean number of PCSI symptoms		one week and month following intervention
Mean number of school days missed		one month following intervention
Number of days of sport activity restriction		1 month following intervention
Time before full recovery	According to the parents	One month following intervention
Healthcare utilization	Proportion of participants who consulted a health resource.	One month following intervention
Side effects	Side effects will include, in addition to symptoms related to mTBI,proportion of participants who complained of diarrhea or constipation (binary answer).	one week and month following intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who complete the assessment at one week following intervention	the main objective of the pilot study is to evaluate the feasibility of the randomized controlled trial. Accordingly, the primary outcome of the pilot study will be the proportion of participants who complete the assessment at one week following intervention	One week following intervention
Proportion of eligible children who were not included	This is the proportion of eligible children who were not included and reasons for non-inclusion.	At baseline
Compliance with study medication	Proportion of patients who tolerated their medication and proportion of patients randomized to the control group who received ondansetron	One week following intervention

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Investigators: Principal Investigator: Jocelyn Gravel, MD, CHU Sainte-JUstine, University of Montreal

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: March 18, 2013
• First Submitted That Met QC Criteria: March 19, 2013
• First Posted (ESTIMATE): March 20, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 29, 2015
• Last Update Submitted That Met QC Criteria: September 28, 2015
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Ondansetron; Emergency department; Mild traumatic brain injury; Brain concussion; Post-concussion syndrome
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: ZOF2013; 9427-c2686-28c (OTHER: Health Canada)