Trial Outcomes & Findings for Subdissociative Dose Ketamine for Treatment of Acute Pain in Subjects With Chronic Pain (NCT NCT02920528)

Results Overview

The primary endpoint was clinically significant pain relief defined a priori as a decrease in the pain VAS of at least 20 mm from baseline, which was arbitrarily chosen as the minimal amount that may be important to this group of patients and was extrapolated from studies of acute pain management in the ED. Using an effect size of 20-mm change in VAS as the marker for a successful outcome and the proportion of successes by group as the analysis point, we performed a power analysis using three groups: 0.5 mg/kg ketamine, 0.25 mg/kg ketamine, and placebo and found that a sample size of 96 subjects would be required to detect a statistically significant difference among groups with a power of 90% (a = 0.05). Expecting a loss of 10% of subjects due to patient withdrawal or incomplete data, 106 subjects were recruited. Only subjects who completed the 60-minute study and had data recorded for each of the time points were included in the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

106 participants

Primary outcome timeframe

60 minutes

Results posted on

2021-04-15

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine
Overall Study STARTED	35	36	35
Overall Study COMPLETED	32	35	30
Overall Study NOT COMPLETED	3	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine
Overall Study Incomplete Data	1	1	1
Overall Study Adverse Event	0	0	3
Overall Study Did not meet inclusion criteria	2	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=32 Participants placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine n=35 Participants 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine n=30 Participants 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Total n=97 Participants Total of all reporting groups
Age, Customized	47.6 years STANDARD_DEVIATION 15 • n=32 Participants	44.3 years STANDARD_DEVIATION 11.2 • n=35 Participants	47.8 years STANDARD_DEVIATION 11.5 • n=30 Participants	46.5 years STANDARD_DEVIATION 12.6 • n=97 Participants
Sex: Female, Male Female	18 Participants n=32 Participants	21 Participants n=35 Participants	18 Participants n=30 Participants	57 Participants n=97 Participants
Sex: Female, Male Male	14 Participants n=32 Participants	14 Participants n=35 Participants	12 Participants n=30 Participants	40 Participants n=97 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	32 participants n=32 Participants	35 participants n=35 Participants	30 participants n=30 Participants	97 participants n=97 Participants
Baseline Pain as measured by validated Visualized Analog Scale (0 to 100 mm)	91.2 units on a scale STANDARD_DEVIATION 9.4 • n=32 Participants	93.2 units on a scale STANDARD_DEVIATION 8.9 • n=35 Participants	91.4 units on a scale STANDARD_DEVIATION 8.5 • n=30 Participants	91.9 units on a scale STANDARD_DEVIATION 8.9 • n=97 Participants

PRIMARY outcome

Timeframe: 60 minutes

The primary endpoint was clinically significant pain relief defined a priori as a decrease in the pain VAS of at least 20 mm from baseline, which was arbitrarily chosen as the minimal amount that may be important to this group of patients and was extrapolated from studies of acute pain management in the ED. Using an effect size of 20-mm change in VAS as the marker for a successful outcome and the proportion of successes by group as the analysis point, we performed a power analysis using three groups: 0.5 mg/kg ketamine, 0.25 mg/kg ketamine, and placebo and found that a sample size of 96 subjects would be required to detect a statistically significant difference among groups with a power of 90% (a = 0.05). Expecting a loss of 10% of subjects due to patient withdrawal or incomplete data, 106 subjects were recruited. Only subjects who completed the 60-minute study and had data recorded for each of the time points were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine n=35 Participants 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine n=30 Participants 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine
To Compare the Percentage of Subjects Who Achieved Significant Pain Relief Between the 3 Treatment Groups as Measured by a Visual Analog Pain Scale at 60 Minutes A Decrease of at Least 20 mm on the VAS Will be Considered "Significant" Pain Relief	13 Participants	28 Participants	25 Participants

SECONDARY outcome

Timeframe: 1 hour

Subjects will be continuously assessed for complications secondary to the sub-dissociative ketamine

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine n=35 Participants 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine n=30 Participants 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine
Assess the Risk for Adverse Events Associated With Sub-dissociative Dose Ketamine	1 recorded adverse events	14 recorded adverse events	12 recorded adverse events

POST_HOC outcome

Timeframe: 24 - 48 hours after study drug infusion

Subjects were contacted by phone 24 - 48 hours after the completion of the study infusion. Subjects were asked to score their pain on 10-point numeric rating scale where 0 represented no pain and 10 represented the worst pain they could be having. Pain score was recorded in increments of 1 from 0 - 10. Results were compared between groups using the Mann-Whitney U-test.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine n=31 Participants 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine n=28 Participants 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine
Follow-up Pain Scores Obtained by Telephone at 24 - 48 Hours	5 units on a scale Interval 4.0 to 8.0	5 units on a scale Interval 4.0 to 7.0	6 units on a scale Interval 3.0 to 8.0

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Very Low Dose Ketamine

Serious events: 14 serious events

Other events: 0 other events

Deaths: 0 deaths

Low Dose Ketamine

Serious events: 12 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=32 participants at risk placebo controlled arm Placebo: Normal Saline	Very Low Dose Ketamine n=35 participants at risk 0.25 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine	Low Dose Ketamine n=30 participants at risk 0.50 mg/kg of sub-dissociative ketamine as an experimental arm Ketamine: sub-dissociative ketamine
Gastrointestinal disorders Nausea	0.00% 0/32 • Up to 48 hours after study enrollment	8.6% 3/35 • Number of events 3 • Up to 48 hours after study enrollment	10.0% 3/30 • Number of events 3 • Up to 48 hours after study enrollment
Nervous system disorders Dizziness	3.1% 1/32 • Number of events 1 • Up to 48 hours after study enrollment	22.9% 8/35 • Number of events 8 • Up to 48 hours after study enrollment	10.0% 3/30 • Number of events 3 • Up to 48 hours after study enrollment
Nervous system disorders Hallucinations	0.00% 0/32 • Up to 48 hours after study enrollment	0.00% 0/35 • Up to 48 hours after study enrollment	6.7% 2/30 • Number of events 2 • Up to 48 hours after study enrollment
Nervous system disorders Anxiety	0.00% 0/32 • Up to 48 hours after study enrollment	0.00% 0/35 • Up to 48 hours after study enrollment	3.3% 1/30 • Number of events 1 • Up to 48 hours after study enrollment
Nervous system disorders Anxiety and Dizziness	0.00% 0/32 • Up to 48 hours after study enrollment	2.9% 1/35 • Number of events 1 • Up to 48 hours after study enrollment	6.7% 2/30 • Number of events 2 • Up to 48 hours after study enrollment
Nervous system disorders Anxiety and Palpitations	0.00% 0/32 • Up to 48 hours after study enrollment	2.9% 1/35 • Number of events 1 • Up to 48 hours after study enrollment	0.00% 0/30 • Up to 48 hours after study enrollment
Nervous system disorders Dysphoria	0.00% 0/32 • Up to 48 hours after study enrollment	2.9% 1/35 • Number of events 1 • Up to 48 hours after study enrollment	3.3% 1/30 • Number of events 1 • Up to 48 hours after study enrollment

Other adverse events

Adverse event data not reported

Additional Information

David Tanen

Lundquist Institute

Phone: 310-222-3624

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place