Trial Outcomes & Findings for Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department (NCT NCT02489630)

Results Overview

Patient-reported pain scores on numerical rating scale (NRS) -11 pain scale (where 0 indicates no pain at all, 10 indicates the most severe pain). "Initial" group were patients enrolled and randomized in to the study, assessments were taken at the time of enrollment/randomization in to the study (up to 20 min prior to T=0). T = 0 min assessments were conducted at the time of medication administration (study allowed for an up to 20-minute delay in receiving study drug in order to retrieve study drug from secure storage, nursing documentation and patient verification prior to administration).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

116 participants

Primary outcome timeframe

20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration

Results posted on

2021-03-12

Participant Flow

Participant milestones

Participant milestones
Measure	Ketamine 0.1 mg/kg ketamine + opiate analgesic Ketamine: 0.1mg/kg ketamine IV opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request	Placebo 0.1 mL/kg normal saline + opiate analgesic Normal Saline: 1ml/kg normal saline placebo opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request
Overall Study STARTED	53	63
Overall Study COMPLETED	51	61
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ketamine 0.1 mg/kg ketamine + opiate analgesic Ketamine: 0.1mg/kg ketamine IV opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request	Placebo 0.1 mL/kg normal saline + opiate analgesic Normal Saline: 1ml/kg normal saline placebo opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request
Overall Study Oversedation	1	1
Overall Study Time to med. admin. > protocol limit	1	1

Baseline Characteristics

Low Dose Ketamine as an Adjunct to Opiates for Acute Pain in the Emergency Department

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ketamine n=53 Participants 0.1 mg/kg ketamine + opiate analgesic Ketamine: 0.1mg/kg ketamine IV opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request	Placebo n=63 Participants 0.1 mL/kg normal saline + opiate analgesic Normal Saline: 1ml/kg normal saline placebo opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request	Total n=116 Participants Total of all reporting groups
Age, Continuous	43.77 years n=93 Participants	41.43 years n=4 Participants	42.46 years n=27 Participants
Sex: Female, Male Female	22 Participants n=93 Participants	29 Participants n=4 Participants	51 Participants n=27 Participants
Sex: Female, Male Male	31 Participants n=93 Participants	34 Participants n=4 Participants	65 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=93 Participants	63 Participants n=4 Participants	114 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	53 participants n=93 Participants	63 participants n=4 Participants	116 participants n=27 Participants

PRIMARY outcome

Timeframe: 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration

Population: Total number of study subjects; received intervention or placebo.

Patient-reported pain scores on numerical rating scale (NRS) -11 pain scale (where 0 indicates no pain at all, 10 indicates the most severe pain). "Initial" group were patients enrolled and randomized in to the study, assessments were taken at the time of enrollment/randomization in to the study (up to 20 min prior to T=0). T = 0 min assessments were conducted at the time of medication administration (study allowed for an up to 20-minute delay in receiving study drug in order to retrieve study drug from secure storage, nursing documentation and patient verification prior to administration).

Outcome measures

Outcome measures
Measure	Ketamine n=53 Participants Patients receiving study intervention	Placebo n=63 Participants Patients not receiving study intervention
Change in Level of Pain Control as Reported on the NRS-11 Initial	9.38 Units on a scale (1-10) Standard Deviation 0.97	9.44 Units on a scale (1-10) Standard Deviation 1.43
Change in Level of Pain Control as Reported on the NRS-11 T = 0 min	7.51 Units on a scale (1-10) Standard Deviation 1.53	8.10 Units on a scale (1-10) Standard Deviation 1.30
Change in Level of Pain Control as Reported on the NRS-11 T = 30 min	5.25 Units on a scale (1-10) Standard Deviation 2.58	2.27 Units on a scale (1-10) Standard Deviation 0.84
Change in Level of Pain Control as Reported on the NRS-11 T = 60 min	5.31 Units on a scale (1-10) Standard Deviation 2.79	6.18 Units on a scale (1-10) Standard Deviation 2.68
Change in Level of Pain Control as Reported on the NRS-11 T = 90 min	4.51 Units on a scale (1-10) Standard Deviation 2.63	6.21 Units on a scale (1-10) Standard Deviation 2.63
Change in Level of Pain Control as Reported on the NRS-11 T = 120 min	4.24 Units on a scale (1-10) Standard Deviation 2.95	5.68 Units on a scale (1-10) Standard Deviation 2.30

PRIMARY outcome

Timeframe: 0 min, 30 min, 60 min, 90 min, 120 min post medication administration

Population: Study subject-reported satisfaction with their pain control beginning at T = 30 minutes post-medication administration. Some study subjects were discharged, admitted or went to the operating room prior to this time point.

Patient-reported score regarding satisfaction with pain control, reported on a 4-point Likert scale (1-4, where 1 is the lowest satisfaction score possible and 4 is the highest satisfaction score possible). No data is reported for T = 0 min, as that assessment was conducted concurrently with initial medication dosing (since patients were at that point receiving their first pain control efforts, they could not yet assess their satisfaction with those efforts).

Outcome measures

Outcome measures
Measure	Ketamine n=50 Participants Patients receiving study intervention	Placebo n=61 Participants Patients not receiving study intervention
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale T = 90 min	2.54 Units on a scale (1-4) Standard Deviation 0.65	2.38 Units on a scale (1-4) Standard Deviation 0.64
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale T = 60 min	2.38 Units on a scale (1-4) Standard Deviation 0.76	2.33 Units on a scale (1-4) Standard Deviation 0.88
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale T = 30 min	2.09 Units on a scale (1-4) Standard Deviation 0.88	2.27 Units on a scale (1-4) Standard Deviation 1.43
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale T = 120 min	2.66 Units on a scale (1-4) Standard Deviation 0.67	2.52 Units on a scale (1-4) Standard Deviation 0.50

SECONDARY outcome

Timeframe: 20 mins pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration

Population: Total number of patients receiving study intervention or placebo (less the two patients who were enrolled but did not receive medication within the protocol-defined time limit.

Average difference in opiate dosage between study arms, calculated in morphine equivalents. "Initial" indicates at first dose of opioid administration, up to 20 mins prior to study drug administration, and from 0 min to 120 min after study drug administration.

Outcome measures

Outcome measures
Measure	Ketamine n=52 Participants Patients receiving study intervention	Placebo n=62 Participants Patients not receiving study intervention
Difference in Opiate Dosage Between Study Arms in Morphine Equivalents Initial Narcotic Dosage	5.41 Milligrams of Morphine Equivalent Standard Deviation 2.77	5.83 Milligrams of Morphine Equivalent Standard Deviation 2.27
Difference in Opiate Dosage Between Study Arms in Morphine Equivalents Total Narcotic Dosage	9.95 Milligrams of Morphine Equivalent Standard Deviation 5.83	12.81 Milligrams of Morphine Equivalent Standard Deviation 6.81

Adverse Events

Ketamine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Karen J Bowers, co-PI

Virginia Tech SOM / Carilion Clinic (prior)

Phone: 678-591-7280

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place