Trial Outcomes & Findings for Ketamine Administration for Postoperative Pain Management in Patients Undergoing Knee Arthroplasty (NCT NCT07059429)
NCT ID: NCT07059429
Last Updated: 2026-03-02
Results Overview
The total dose of opioid analgesics (calculated in milligrams of morphine equivalents) administered to each patient during the first 24 hours after knee arthroplasty.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
100 participants
Primary outcome timeframe
24 hours postoperatively
Results posted on
2026-03-02
Participant Flow
Patients undergoing knee arthroplasty at Pirogov National Medical and Surgical Center were sequentially recruited and randomly assigned to intervention or control group.
Participant milestones
| Measure |
Ketamine Plus Standard Analgesia
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
50
|
|
Overall Study
COMPLETED
|
49
|
46
|
|
Overall Study
NOT COMPLETED
|
1
|
4
|
Reasons for withdrawal
| Measure |
Ketamine Plus Standard Analgesia
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
3
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
Total
n=95 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.1 years
STANDARD_DEVIATION 8.24 • n=49 Participants
|
64.83 years
STANDARD_DEVIATION 8.71 • n=46 Participants
|
65 years
STANDARD_DEVIATION 8.47 • n=95 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=49 Participants
|
35 Participants
n=46 Participants
|
76 Participants
n=95 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=49 Participants
|
11 Participants
n=46 Participants
|
19 Participants
n=95 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Russia
|
49 Participants
n=49 Participants
|
46 Participants
n=46 Participants
|
95 Participants
n=95 Participants
|
|
Body Mass Index (BMI)
|
30.97 kg/m²
STANDARD_DEVIATION 13.03 • n=49 Participants
|
31.08 kg/m²
STANDARD_DEVIATION 12.73 • n=46 Participants
|
31.02 kg/m²
STANDARD_DEVIATION 12.88 • n=95 Participants
|
PRIMARY outcome
Timeframe: 24 hours postoperativelyPopulation: Of 100 randomized participants, 5 were excluded from analysis due to protocol violations or incomplete follow-up. The final per-protocol analysis included 49 participants in the ketamine group and 46 participants in the control group (total n=95).
The total dose of opioid analgesics (calculated in milligrams of morphine equivalents) administered to each patient during the first 24 hours after knee arthroplasty.
Outcome measures
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Total Opioid Consumption in Morphine Equivalents Within 24 Hours After Surgery
|
0 mg morphine equivalents (MME)
Inter-Quartile Range 20.4 • Interval 0.0 to 0.0
|
10 mg morphine equivalents (MME)
Inter-Quartile Range 18.7 • Interval 0.0 to 20.0
|
SECONDARY outcome
Timeframe: 2-10 hours and 10-24 hours postoperativelyPopulation: Of 100 randomized participants, 5 were excluded from analysis due to protocol violations or incomplete follow-up. The final per-protocol analysis included 49 participants in the ketamine group and 46 participants in the control group (total n=95).
Pain intensity measured using the 11-point Numeric Rating Scale (NRS), where 0 = no pain and 10 = worst pain imaginable, averaged across two time intervals: 2-10 hours (mean of time points 2, 4, 6, 10h) and 10-24 hours (mean of time points 14, 18, 24h) after surgery.
Outcome measures
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Pain Intensity Assessed by Numeric Rating Scale (NRS)
NRS 10-24 hours
|
1.74 points on a scale
Standard Deviation 1.21
|
2.44 points on a scale
Standard Deviation 1.05
|
|
Pain Intensity Assessed by Numeric Rating Scale (NRS)
NRS 2-10 hours
|
1.91 points on a scale
Standard Deviation 1.29
|
2.83 points on a scale
Standard Deviation 1.15
|
SECONDARY outcome
Timeframe: 24 hours postoperativelyPopulation: Of 100 randomized participants, 5 were excluded from analysis due to protocol violations or incomplete follow-up. The final per-protocol analysis included 49 participants in the ketamine group and 46 participants in the control group (total n=95).
The number of patients experiencing any episode of postoperative nausea or vomiting during the first 24 hours after surgery.
Outcome measures
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Incidence of Postoperative Nausea and Vomiting
|
11 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 0-10 hours and 10-24 hours postoperativelyPopulation: Of 100 randomized participants, 5 were excluded from analysis due to protocol violations or incomplete follow-up. The final per-protocol analysis included 49 participants in the ketamine group and 46 participants in the control group (total n=95).
Number of participants experiencing neuropsychiatric adverse events during 0-10 hours (NPA 0-10 hours) and 10-24 hours (NPA 10-24 hours) after knee arthroplasty.
Outcome measures
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Number of Participants With Neuropsychiatric Adverse Events
NPA 0-10 hours
|
14 Participants
|
3 Participants
|
|
Number of Participants With Neuropsychiatric Adverse Events
NPA 10-24 hours
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 hours postoperativelyPopulation: Of 100 randomized participants, 5 were excluded from analysis due to protocol violations or incomplete follow-up. The final per-protocol analysis included 49 participants in the ketamine group and 46 participants in the control group (total n=95).
The maximum severity of any neuropsychiatric adverse event experienced by a patient, graded according to the Common Terminology Criteria for Adverse Events (CTCAE). The scale ranges from Grade 1 (Mild) to Grade 5 (Death). Specific conditions and symptoms may have values or descriptive comment for each level, but the general guideline is: 1. \- Mild 2. \- Moderate 3. \- Severe 4. \- Life-threatening 5. \- Death
Outcome measures
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Severity of Neuropsychiatric Adverse Events
1 - Mild
|
14 Participants
|
3 Participants
|
|
Severity of Neuropsychiatric Adverse Events
2 - Moderate
|
1 Participants
|
0 Participants
|
|
Severity of Neuropsychiatric Adverse Events
3 - Severe
|
1 Participants
|
0 Participants
|
|
Severity of Neuropsychiatric Adverse Events
4 - Life-threatening
|
0 Participants
Interval 0.0 to 0.0
|
0 Participants
Interval 0.0 to 0.0
|
|
Severity of Neuropsychiatric Adverse Events
5 - Death
|
0 Participants
Interval 0.0 to 0.0
|
0 Participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 24 hours postoperativelyPopulation: Of 100 randomized participants, 5 were excluded from analysis due to protocol violations or incomplete follow-up. The final per-protocol analysis included 49 participants in the ketamine group and 46 participants in the control group (total n=95).
The total cumulative dose of ketamine (in milligrams) administered during the first 24 hours after surgery, including both the continuous infusion and patient-initiated boluses.
Outcome measures
| Measure |
Ketamine Plus Standard Analgesia
n=49 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=46 Participants
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Cumulative Ketamine Dose Administered
|
304 milligrams (mg)
Interval 271.0 to 341.0
|
0 milligrams (mg)
Interval 0.0 to 0.0
|
Adverse Events
Ketamine Plus Standard Analgesia
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Standard Analgesia Alone
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ketamine Plus Standard Analgesia
n=50 participants at risk
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=50 participants at risk
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Psychiatric disorders
Hallucinations
|
2.0%
1/50 • From randomization until 24 hours post-operative
Neuropsychiatric adverse events including hallucinations and post-traumatic stress reaction (PTSR) were systematically assessed and recorded throughout the study period. Additionally, serious adverse events such as thrombotic complications and inadequate regional anesthesia were documented.
|
0.00%
0/50 • From randomization until 24 hours post-operative
Neuropsychiatric adverse events including hallucinations and post-traumatic stress reaction (PTSR) were systematically assessed and recorded throughout the study period. Additionally, serious adverse events such as thrombotic complications and inadequate regional anesthesia were documented.
|
|
Vascular disorders
Arterial Thrombosis
|
0.00%
0/50 • From randomization until 24 hours post-operative
Neuropsychiatric adverse events including hallucinations and post-traumatic stress reaction (PTSR) were systematically assessed and recorded throughout the study period. Additionally, serious adverse events such as thrombotic complications and inadequate regional anesthesia were documented.
|
2.0%
1/50 • From randomization until 24 hours post-operative
Neuropsychiatric adverse events including hallucinations and post-traumatic stress reaction (PTSR) were systematically assessed and recorded throughout the study period. Additionally, serious adverse events such as thrombotic complications and inadequate regional anesthesia were documented.
|
Other adverse events
| Measure |
Ketamine Plus Standard Analgesia
n=50 participants at risk
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) plus a continuous intravenous infusion of ketamine using PCA at 0.15 mg/kg/h, with 1 mg boluses available every 5 minutes (maximum daily dose 500 mg), for 24 hours after knee arthroplasty. Morphine 10 mg intramuscularly (IM) may be administered as needed for rescue therapy.
|
Standard Analgesia Alone
n=50 participants at risk
Participants in this group will receive standardized postoperative pain management (ketoprofen 100 mg twice daily and paracetamol 1000 mg every 8 hours for 24 hours after knee arthroplasty) without ketamine infusion. Morphine 10 mg IM may be administered as needed for rescue therapy.
|
|---|---|---|
|
Surgical and medical procedures
Inadequate Regional Anesthesia
|
0.00%
0/50 • From randomization until 24 hours post-operative
Neuropsychiatric adverse events including hallucinations and post-traumatic stress reaction (PTSR) were systematically assessed and recorded throughout the study period. Additionally, serious adverse events such as thrombotic complications and inadequate regional anesthesia were documented.
|
6.0%
3/50 • From randomization until 24 hours post-operative
Neuropsychiatric adverse events including hallucinations and post-traumatic stress reaction (PTSR) were systematically assessed and recorded throughout the study period. Additionally, serious adverse events such as thrombotic complications and inadequate regional anesthesia were documented.
|
Additional Information
Ivan Shcheparev, MD, PhD
Pirogov National Medical and Surgical Center
Phone: +7 (901) 908-90-88
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place