Sub-dissociative Ketamine for the Management of Acute Pediatric Pain

• ClinicalTrials.gov Identifier: NCT01951963
• Recruitment Status: Completed
• First Posted: September 27, 2013
• Results First Posted: October 16, 2017
• Last Update Posted: July 3, 2018
• Sponsor: HealthPartners Institute
• Information provided by (Responsible Party): HealthPartners Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Pain
• Interventions: Drug: Ketamine; Drug: Morphine
• Enrollment: 77

Participant Flow

Recruitment Details
Pre-assignment Details	77 met eligibility criteria and 63 were randomized to one of the two study groups.

Arm/Group Title	Ketamine	Morphine
Arm/Group Description	Ketamine, single dose, 0.3 mg/kg, IV The final sample included 40 subjects, 20 in the Ketamine group. The baseline characteristics were similar between the two groups. These patients were randomized to receive a single bolus of ketamine (0.3 mg/kg). These are standard recommended pediatric weight-based analgesic doses of Ketamine. Patient weight was obtained by the treating RN using a scale or Broselow tape. A blinded 10mL syringe containing study drug was prepared and delivered to the bedside by a pharmacist. After administration of study drug all future analgesic doses were restricted to morphine and were given at the discretion of the treatment team.	Morphine, single dose, 0.05 mg/kg, IV The final sample included 40 subjects, 20 in the Morphine group. The baseline characteristics were similar between the two groups. These patients were randomized to receive a single bolus of morphine (0.05mg/kg). These are standard recommended pediatric weight-based analgesic doses of Morphine. Patient weight was obtained by the treating RN using a scale or Broselow tape. A blinded 10mL syringe containing study drug was prepared and delivered to the bedside by a pharmacist. After administration of study drug all future analgesic doses were restricted to morphine and were given at the discretion of the treatment team.
Period Title: Overall Study
Started	31	32
Completed	31	32
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Ketamine	Morphine	Total
Arm/Group Description		Ketamine, single dose, 0.3 mg/kg, IV The final sample included 40 subjects, 20 in the Ketamine group. Inclusion criteria was defined as, patients age 3-17 years old, medical or traumatic condition requiring intravenous opioid analgesics, ability to obtain consent from parents and assent from the patient. The baseline characteristics were similar between the two groups. These patients were randomized to receive a single bolus of ketamine (0.3 mg/kg). These are standard recommended pediatric weight-based analgesic doses of Ketamine. Patient weight was obtained by the treating RN using a scale or Broselow tape. A blinded 10mL syringe containing study drug was prepared and delivered to the bedside by a pharmacist. After administration of study drug all future analgesic doses were restricted to morphine and were given at the discretion of the treatment team.	Morphine, single dose, 0.05 mg/kg, IV The final sample included 40 subjects, 20 in the Morphine group. The baseline characteristics were similar between the two groups. These patients were randomized to receive a single bolus of morphine (0.05mg/kg). These are standard recommended pediatric weight-based analgesic doses of Morphine. Patient weight was obtained by the treating RN using a scale or Broselow tape. A blinded 10mL syringe containing study drug was prepared and delivered to the bedside by a pharmacist. After administration of study drug all future analgesic doses were restricted to morphine and were given at the discretion of the treatment team.	Total of all reporting groups
Overall Number of Baseline Participants		31	32	63
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
	<=18 years	31 100.0%	32 100.0%	63 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	31 participants	32 participants	63 participants
		13.3 (3.6)	12.7 (3.7)	13.0 (3.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
	Female	12 38.7%	9 28.1%	21 33.3%
	Male	19 61.3%	23 71.9%	42 66.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	31 participants	32 participants	63 participants
		31	32	63

Outcome Measures

1. Primary Outcome

Title	Cumulative Narcotic Consumption
Description	All opioids administered were converted to morphine equivalents in milligrams (eq. mg) via standard equianalgesic calculations. Pre-study drug opioids information was also collected.The number of subjects who received a morphine dose after administration of the study drug, both within one hour or at all was included in the outcome measure results.
Time Frame	3 hours post study drug administration

Outcome Measure Data

Analysis Population Description

The number of subjects in each group who received at least one dose of opioids post study drug.

Arm/Group Title	Ketamine	Morphine
Arm/Group Description:	Ketamine, single dose, 0.3 mg/kg, IV Ketamine prospective, double blind, randomized control trial. After informed consent, patients 3-17 years old requiring intravenous analgesics were randomized to receive either a single dose of 0.3mg/kg ketamine or 0.05mg/kg morphine in addition to standard opioid based analgesia. These weight-based doses of Ketamine and Morphine are the standard recommended doses from the Lexicomp Drug Reference Handbook, Pediatric and Neonatal Dosing (2011-2012).	Morphine, single dose, 0.05 mg/kg, IV Morphine prospective, double blind, randomized control trial. After informed consent, patients 3-17 years old requiring intravenous analgesics were randomized to receive either a single dose of 0.3mg/kg ketamine or 0.05mg/kg morphine in addition to standard opioid based analgesia. These weight-based doses of Ketamine and Morphine are the standard recommended doses from the Lexicomp Drug Reference Handbook, Pediatric and Neonatal Dosing (2011-2012).
Overall Number of Participants Analyzed	31	32
Measure Type: Count of Participants; Unit of Measure: Participants
	19 61.3%	14 43.8%

2. Primary Outcome

Title	Adverse Drug Reaction
Description	Rate of pain medication related adverse events during their ED stay and at 24 hours post discharge from the ED. the research team will complete the Adverse Event case report form to determine any adverse events occurring during the study period. Family members will be contacted via telephone 24 hours (±8 hours) following their visit in the Emergency Department to complete the Discharge Adverse Event case report form.
Time Frame	3 hours post study drug administration

Outcome Measure Data

Analysis Population Description

Rate of pain medication related adverse events during their ED stay and at 24 hours post discharge from the ED will be compared using unadjusted Fisher's exact of a composite measure (≤ 1 events vs. > 1).

Arm/Group Title	Ketamine	Morphine
Arm/Group Description:	Ketamine, single dose, 0.3 mg/kg, IV Ketamine	Morphine, single dose, 0.05 mg/kg, IV Morphine
Overall Number of Participants Analyzed	31	32
Measure Type: Count of Participants; Unit of Measure: Participants
	2 6.5%	3 9.4%

3. Other Pre-specified Outcome

Title	Pain Scale Rating Agreement Among Patient, Parent, and Research Staff
Description	FLACC scores were assessed on the patient using the FLACC scale (0-10) by the parent, treating RN/trained research assistant.; FLACC - Parents 30 Minutes Post dose; FLACC - Staff 30 Minutes Post dose Wong-Baker Faces scale is a self-assessment of pain Scale of 1-10 pain.
Time Frame	Up to 3 hours post pain medication administration

Outcome Measure Data

Analysis Population Description

Wong-Baker Faces scale is a self-assessment of pain Scale. FLACC Score (FLACC = Face, Legs, Activity, Crying and Consolability) is a behavioral observational pain rating scale that looks for specific behaviors and scores them. Both scales are scored 0-10 with 0 representing no pain. Lower scores are better outcomes.

Arm/Group Title	Ketamine	Morphine
Arm/Group Description:	Ketamine, single dose, 0.3 mg/kg, IV The final sample included 40 subjects, 20 in the Ketamine group. The baseline characteristics were similar between the two groups. These patients were randomized to receive a single bolus of ketamine (0.3 mg/kg). These are standard recommended pediatric weight-based analgesic doses of Ketamine. Patient weight was obtained by the treating RN using a scale or Broselow tape. A blinded 10mL syringe containing study drug was prepared and delivered to the bedside by a pharmacist. After administration of study drug all future analgesic doses were restricted to morphine and were given at the discretion of the treatment team.	Morphine, single dose, 0.05 mg/kg, IV The final sample included 40 subjects, 20 in the Morphine group. The baseline characteristics were similar between the two groups. These patients were randomized to receive a single bolus of morphine (0.05mg/kg). These are standard recommended pediatric weight-based analgesic doses of Morphine. Patient weight was obtained by the treating RN using a scale or Broselow tape. A blinded 10mL syringe containing study drug was prepared and delivered to the bedside by a pharmacist. After administration of study drug all future analgesic doses were restricted to morphine and were given at the discretion of the treatment team.
Overall Number of Participants Analyzed	31	32
Mean (Standard Deviation); Unit of Measure: Scores on a scale
FLACC - Staff 30 Minutes Post dose	1.1 (1.7)	1.1 (1.6)
FLACC - Parents 30 Minutes Post dose	2.0 (2.1)	1.9 (1.9)
Wong-Baker Faces pain scale changes	-3.5 (2.4)	-3.7 (2.4)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ketamine		Morphine
Arm/Group Description	Ketamine, single dose, 0.3 mg/kg, IV Ketamine		Morphine, single dose, 0.05 mg/kg, IV Morphine
All-Cause Mortality
	Ketamine		Morphine
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Ketamine		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0.00%)		0/32 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ketamine		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.45%)		2/32 (6.25%)
Gastrointestinal disorders
vomiting/nausea †	0/31 (0.00%)	0	1/32 (3.13%)	1
Skin and subcutaneous tissue disorders
Allergic Reaction to study drug † [1]	2/31 (6.45%)	2	2/32 (6.25%)	2
† Indicates events were collected by systematic assessment; [1] Rash

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Aaron Burnett
• Organization: Health Partners
• Phone: 651-254-5304
• EMail: Aaron.M.Burnett@HealthPartners.Com

• Responsible Party: HealthPartners Institute
• ClinicalTrials.gov Identifier: NCT01951963
• Other Study ID Numbers: A12-158
• First Submitted: September 24, 2013
• First Posted: September 27, 2013
• Results First Submitted: February 16, 2017
• Results First Posted: October 16, 2017
• Last Update Posted: July 3, 2018