Trial Outcomes & Findings for Efficacy Study of Ketamine for Postoperative Pain in Opioid Dependent Patients (NCT NCT01591382)

Results Overview

Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for "worst," "average," and "least" pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average postoperative pain score for each treatment arm is reported.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

64 participants

Primary outcome timeframe

Participants were followed for the duration of hospital stay, an average of approximately 3 days.

Results posted on

2017-03-22

Participant Flow

Participant milestones

Participant milestones
Measure	Ketamine Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Overall Study STARTED	32	32
Overall Study COMPLETED	29	30
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ketamine Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Overall Study Discharged Prior to Study Completion	2	1
Overall Study Participant Opted for Morphine PCA	1	1

Baseline Characteristics

Efficacy Study of Ketamine for Postoperative Pain in Opioid Dependent Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ketamine n=29 Participants Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=30 Participants Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Total n=59 Participants Total of all reporting groups
Age, Continuous	48.5 years STANDARD_DEVIATION 11.9 • n=5 Participants	55 years STANDARD_DEVIATION 11.2 • n=7 Participants	52.2 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Participants were followed for the duration of hospital stay, an average of approximately 3 days.

Population: All randomized participants who completed the study.

Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for "worst," "average," and "least" pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average postoperative pain score for each treatment arm is reported.

Outcome measures

Outcome measures
Measure	Ketamine n=29 Participants Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=30 Participants Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Average Postoperative Pain Score	6.0 units on a scale Standard Deviation 2.2	7.3 units on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: Participants were followed for the duration of hospital stay, an average of approximately 3 days.

Population: All randomized participants who completed the study.

Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for "worst," "average," and "least" pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average worst postoperative pain score for each treatment arm is reported.

Outcome measures

Outcome measures
Measure	Ketamine n=29 Participants Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=30 Participants Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Worst Postoperative Pain Score	8.7 units on a scale Standard Deviation 2.0	9.0 units on a scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: Participants were followed for the duration of hospital stay, an average of approximately 3 days.

Population: All randomized participants who completed the study.

Postoperative pain scores were collected once per day during morning rounds for the preceding 24 hours. Participant were asked to provide pain scores for "worst," "average," and "least" pain using the 11-point Numerical Rating Scale (NRS), where 0 represents the absence of pain and 10 is worst possible pain. The average least postoperative pain score for each treatment arm is reported.

Outcome measures

Outcome measures
Measure	Ketamine n=29 Participants Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=30 Participants Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Least Postoperative Pain Score	4.4 units on a scale Standard Deviation 3.1	5.6 units on a scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: For 24 hours following surgery

Population: All randomized participants who completed the study.

Opioid use is defined as the total milligrams of hydromorphone plus other home or oral opioid used per 24 hours, converted to oral morphine equivalents.

Outcome measures

Outcome measures
Measure	Ketamine n=29 Participants Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=30 Participants Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
24-Hour Postoperative Opioid Use	726 oral morphine mg equivalents Standard Deviation 489	770 oral morphine mg equivalents Standard Deviation 560

SECONDARY outcome

Timeframe: Participants were followed for the duration of hospital stay, an average of approximately 3 days.

Population: All randomized participants who completed the study and also completed the Side Effects Checklist.

Participants were asked to complete a "Side Effects Checklist" to assess for any unwanted side effects (AEs) of drugs that were administered. The determination of whether or not an AE was treatment related was at the discretion of the Investigator.

Outcome measures

Outcome measures
Measure	Ketamine n=27 Participants Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=28 Participants Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Number of Participants With Treatment Related Adverse Events (AEs) Respiratory depression	0 participants	0 participants
Number of Participants With Treatment Related Adverse Events (AEs) Hallucination	1 participants	0 participants
Number of Participants With Treatment Related Adverse Events (AEs) Pruritis	5 participants	2 participants
Number of Participants With Treatment Related Adverse Events (AEs) Sedation	25 participants	24 participants
Number of Participants With Treatment Related Adverse Events (AEs) Nausea	7 participants	5 participants

Adverse Events

Ketamine

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ketamine n=27 participants at risk Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=28 participants at risk Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Injury, poisoning and procedural complications Drug administration error	0.00% 0/27 Adverse events are reported for all randomized participants who completed the study and also completed the Side Effects Checklist.	3.6% 1/28 Adverse events are reported for all randomized participants who completed the study and also completed the Side Effects Checklist.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/27 Adverse events are reported for all randomized participants who completed the study and also completed the Side Effects Checklist.	3.6% 1/28 Adverse events are reported for all randomized participants who completed the study and also completed the Side Effects Checklist.

Other adverse events

Other adverse events
Measure	Ketamine n=27 participants at risk Hydromorphone PCA and ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.	Placebo n=28 participants at risk Hydromorphone PCA and placebo-matching ketamine intravenous (IV) infusion 0.2 mg/kg/hr for 24-48 hours postoperatively.
Skin and subcutaneous tissue disorders Pruritis	18.5% 5/27 Adverse events are reported for all randomized participants who completed the study and also completed the Side Effects Checklist.	7.1% 2/28 Adverse events are reported for all randomized participants who completed the study and also completed the Side Effects Checklist.

Additional Information

Dr. Srdjan S. Nedeljkovic

Brigham and Women's Hospital

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place