Predicting Persistent Postconcussive Problems in Pediatrics (5P)

• Sponsor: Children's Hospital of Eastern Ontario (Other)
• Overall Status: Completed
• CT.gov ID: NCT01873287
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other)
• Enrollment: 3,063
• Locations: 9
• Duration (Months): 22
• Patients Per Site: 340.3
• Patients Per Site Per Month: 15.5

Study Details

Study Description

Brief Summary

Concussion, a mild traumatic injury common in children and adolescents, is a complex pathophysiological process affecting the brain. The lay press is inundated with reports of tragic consequences of concussion, and children are not immune.

Persistent postconcussive symptoms (PCS) is defined as the persistence of somatic, cognitive, physical, psychological or behavioural changes lasting more than one month following injury. PCS significantly impacts children and their family's quality of life through school absenteeism, depressed mood and loss of activities.

Validated, easy-to-use prognosticators do not exist for clinicians to identify children at highest risk for PCS. As a result,physicians cannot accurately inform children and parents whether they should expect longer symptoms, nor initiate pharmacotherapy or other management to reduce the occurrence or severity of PCS.

The investigators objective is to derive and validate a clinical prediction rule for the development of PCS in children and adolescents presenting to the emergency department (ED) following acute head injury. The investigators have three aims: (1) determine PCS incidence at one-month follow-up in children aged 5-17 who sustain a concussion; (2) derive a rule to predict PCS from variables present in the history and physical examination; and, (3) assess the accuracy, reliability and acceptability of the prediction rule in a subsequent cohort. Using a prospective, multicentre study at nine large Canadian pediatric EDs, the investigators will recruit the largest prospective epidemiological cohort of children with concussions in the literature.

This work will provide rigorous evidence to determine PCS incidence in children and its impact on quality of life. The results will enable clinicians to identify children at highest risk for PCS, optimize treatment and provide families with realistic anticipatory guidance. This study will also establish a strong and vital evidence base to advance concussion research.

Condition or Disease	Intervention/Treatment	Phase
Concussions; PCS

Detailed Description

The full protocol has been published in BMJ Open (open access):

Zemek R, Osmond MH, Barrowman N for PERC Concussion Team. Predicting and preventing postconcussive problems in paediatrics (5P) study: protocol for a prospective multicentre clinical prediction rule derivation study in children with concussion. BMJ Open. 2013 Aug 1;3(8). pii:e003550. doi: 10.1136/bmjopen-2013-003550. PubMed PMID: 23906960. https://www.ncbi.nlm.nih.gov/pubmed/23906960

The primary outcome results have been published in JAMA (open access):

Zemek R, Barrowman N, Freedman SB, Gravel J, Gagnon I, McGahern C, Aglipay M, Sangha G, Boutis K, Beer D, Craig W, Burns E, Farion KJ, Mikrogianakis A, Barlow K, Dubrovsky AS, Meeuwisse W, Gioia G, Meehan WP 3rd, Beauchamp MH, Kamil Y, Grool AM, Hoshizaki B, Anderson P, Brooks BL, Yeates KO, Vassilyadi M, Klassen T, Keightley M, Richer L, DeMatteo C, Osmond MH; Pediatric Emergency Research Canada (PERC) Concussion Team. Clinical Risk Score for Persistent Postconcussion Symptoms among Children With Acute Concussion in the ED. JAMA. 2016 Mar 8;315(10):1014-25. doi: 10.1001/jama.2016.1203. PubMed PMID: 26954410. http://dx.doi.org/10.1001/jama.2016.1203

Study Design

• Study Type: Observational
• Actual Enrollment: 3063 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Predicting Persistent Postconcussive Problems in Pediatrics: A Clinical Prediction Rule Derivation and Validation Study
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Outcome Measures

Primary Outcome Measures

1. Count of Children Who Have Persistent Post-concussive Symptoms (PCS) at One-month Follow-up. [1 month]

   The primary outcome is the number of of children aged 5 - 17 years who have PCS at one-month follow-up. A PCS case is defined as an increase from pre-concussion baseline of three or more symptoms on the validated PCSI at one-month (consistent with the ICD-10 definition of PCS).

Secondary Outcome Measures

1. Pediatric Quality of Life Inventory (PedsQL) Total Score at 4-weeks Post-injury [1 month]

   The PedsQL™ is a reliable and valid measure of health-related quality of life in healthy children and adolescents and those with acute and/or chronic health conditions. Parent versions exist for children aged 2 to 18 years (in 4 age groups) and child versions for those aged 5 and over. The inventory covers four domains: physical, emotional, social and school. Items are calculated and transformed into an overall score with a range of 0 to 100 points, with more points indicating better quality of life. This secondary outcome measure will be used to determine the impact of PCS on quality of life on patients and families.

2. Neuropsychological Evaluation [1 month and 3 month]

   A separate battery of neuropsychological assessment measures will be administered to those children who choose to participate in this arm of the study. This battery includes measures of intelligence, language, visual-spatial/motor functions, attention, memory/working memory, executive functioning, academic achievement, as well as behavioural/socioemotional functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects presenting to one of the study hospital EDs after sustaining a head injury will be eligible if they:

• are aged 5 to 17 years;

• have a concussion, defined by Zurich consensus statement;22

• suffered the initial injury in the previous 48 hours;

• are proficient in English or French.

Exclusion Criteria: Patients will be excluded if they present with traumatic head injuries with any of the following:

• GCS ≤13; any abnormality on standard neuroimaging studies, including any positive head CT findings (Note: neuroimaging is not required, but may be performed by the clinician if thought to be clinically indicated);

• neurosurgical operative intervention, intubation or PICU care required;

• multi-system injuries with treatment requiring admission to hospital, operating room or procedural sedation in the ED (Note: admission to hospital for observation or management of ongoing concussion symptoms is not an exclusion criteria);

• severe chronic neurological developmental delay resulting in communication difficulties;

• intoxication at the time of ED presentation as per clinician judgment;

• no clear history of trauma as primary event (e.g., seizure, syncope or migraine as primary event);

• previously enrolled in this same study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stollery Children's Hospital	Edmonton	Alberta	Canada
2	Children's Hospital of Winnipeg	Winnipeg	Manitoba	Canada
3	IWK Health Sciences Centre	Halifax	Nova Scotia	Canada
4	Alberta Children's Hospital	Calgary	Ontario	Canada
5	Children's Hospital of Western Ontario	London	Ontario	Canada
6	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
7	The Hospital for Sick Children	Toronto	Ontario	Canada
8	CHU Sainte-Justine	Montreal	Quebec	Canada
9	Montreal Children's Hospital	Montreal	Quebec	Canada

Sponsors and Collaborators

• Children's Hospital of Eastern Ontario
• Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Roger L Zemek, MD, CHEO

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roger Zemek, Pediatric Emergentologist, Division of Emergency Medicine, Children's Hospital of Eastern Ontario
• ClinicalTrials.gov Identifier: NCT01873287
• Other Study ID Numbers: CIHR-302955, CIHR-287347
• First Posted: Jun 10, 2013
• Last Update Posted: Nov 18, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Roger Zemek, Pediatric Emergentologist, Division of Emergency Medicine, Children's Hospital of Eastern Ontario: Concussions; Persistent post-concussion symptoms; PCS; Clinical Prediction Rule

Study Results

Participant Flow

Arm/Group Title	Derivation Arm	Validation Arm
Arm/Group Description	Inclusion criteria. Subjects presenting to one of the study hospital EDs after sustaining a head injury will be eligible if they: (1) are aged 5 to 17 years; (2) have a concussion, defined by Zurich consensus statement; (3) suffered the initial injury in the previous 48 hours; (4) are proficient in English or French. Exclusion criteria. Patients will be excluded if they present with traumatic head injuries with any of the following: GCS ≤13; any abnormality on standard neuroimaging studies,; neurosurgical operative intervention, intubation or PICU care required; multi-system injuries with treatment requiring admission to hospital, operating room or procedural sedation in the ED; severe chronic neurological developmental delay resulting in communication difficulties; intoxication at the time of ED presentation as per clinician judgment; no clear history of trauma as primary event (e.g., seizure, syncope or migraine as primary event); previously enrolled in this same study.	Inclusion criteria. Subjects presenting to one of the study hospital EDs after sustaining a head injury will be eligible if they: (1) are aged 5 to 17 years; (2) have a concussion, defined by Zurich consensus statement; (3) suffered the initial injury in the previous 48 hours; (4) are proficient in English or French. Exclusion criteria. Patients will be excluded if they present with traumatic head injuries with any of the following: GCS ≤13; any abnormality on standard neuroimaging studies,; neurosurgical operative intervention, intubation or PICU care required; multi-system injuries with treatment requiring admission to hospital, operating room or procedural sedation in the ED; severe chronic neurological developmental delay resulting in communication difficulties; intoxication at the time of ED presentation as per clinician judgment; no clear history of trauma as primary event (e.g., seizure, syncope or migraine as primary event); previously enrolled in this same study.
Period Title: Overall Study
STARTED	2006	1057
COMPLETED	1701	883
NOT COMPLETED	305	174

Baseline Characteristics

Arm/Group Title	Derivation Cohort	Validation Cohort	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	2006	1057	3063
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	11.8	12.3	12.0
Sex: Female, Male (Count of Participants)
Female	765 38.1%	440 41.6%	1205 39.3%
Male	1241 61.9%	617 58.4%	1858 60.7%
Region of Enrollment (participants) [Number]
Canada	2006 100%	1057 100%	3063 100%

Outcome Measures

1. Primary Outcome

Title	Count of Children Who Have Persistent Post-concussive Symptoms (PCS) at One-month Follow-up.
Description	The primary outcome is the number of of children aged 5 - 17 years who have PCS at one-month follow-up. A PCS case is defined as an increase from pre-concussion baseline of three or more symptoms on the validated PCSI at one-month (consistent with the ICD-10 definition of PCS).
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Completed 1-month followup.

Arm/Group Title	PPCS in Derivation	PPCS in Validation
Arm/Group Description	August 2013 to September 2014	October 2014 to June 2015
Measure Participants	1701	883
Count of Participants [Participants]	510 25.4%	291 27.5%

2. Secondary Outcome

Title	Pediatric Quality of Life Inventory (PedsQL) Total Score at 4-weeks Post-injury
Description	The PedsQL™ is a reliable and valid measure of health-related quality of life in healthy children and adolescents and those with acute and/or chronic health conditions. Parent versions exist for children aged 2 to 18 years (in 4 age groups) and child versions for those aged 5 and over. The inventory covers four domains: physical, emotional, social and school. Items are calculated and transformed into an overall score with a range of 0 to 100 points, with more points indicating better quality of life. This secondary outcome measure will be used to determine the impact of PCS on quality of life on patients and families.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Completed PedsQL at 1-month post-concussion.

Arm/Group Title	Participants With PPCS	Participants Without PPCS
Arm/Group Description	The primary outcome measure, PPCS, was defined in keeping with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) definition of postconcussion syndrome, which requires persistence beyond 4 weeks of at least 3 symptoms compared with state of being prior to the injury. In the study, an individual symptom was defined as a positive difference between the patient-reported current minus the perceived preinjury symptom rating on PCSI; both were completed 28 days after the injury.	Less than 3 symptoms compared with state of being prior to the injury at 28 days. In the study, an individual symptom was defined as a positive difference between the patient-reported current minus the perceived preinjury symptom rating on PCSI; both were completed 28 days after the injury.
Measure Participants	510	1157
Mean (95% Confidence Interval) [units on a scale]	70.0	80.3

3. Secondary Outcome

Title	Neuropsychological Evaluation
Description	A separate battery of neuropsychological assessment measures will be administered to those children who choose to participate in this arm of the study. This battery includes measures of intelligence, language, visual-spatial/motor functions, attention, memory/working memory, executive functioning, academic achievement, as well as behavioural/socioemotional functioning.
Time Frame	1 month and 3 month

Outcome Measure Data

Analysis Population Description

Participants assessed at 4- and 12-weeks post-injury using direct, standardized measures of intellectual functioning, verbal memory, executive functioning, attention/working memory, processing speed and fine motor abilities.

Arm/Group Title	Number of Children With Neuropsychological Impairment
Arm/Group Description	Incidence of neuropsychological impairment was determined using the Neuropsychological Impairment (NPI) rule (Beauchamp et al., 2015) and multiple hierarchical logistic and linear regressions were performed to assess the contribution of pre-morbid factors, acute symptoms, and acute cognitive testing to neuropsychological impairment and performance.
Measure Participants	311
Count of Participants [Participants]	32 1.6%

Adverse Events

Arm/Group Title	Participants
Arm/Group Description	All enrolled participants.
All Cause Mortality
	Participants
	Affected / at Risk (%)	# Events
Total	0/3063 (0%)
Serious Adverse Events
	Participants
	Affected / at Risk (%)	# Events
Total	0/3063 (0%)
Other (Not Including Serious) Adverse Events
	Participants
	Affected / at Risk (%)	# Events
Total	0/3063 (0%)

Limitations/Caveats

Selection bias (children presenting to ED as compared to general primary care) may limit generalizability. There is no control group (e.g., orthopedic injury) to compare symptom scores. Socio-economic status and race data were not collected.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.