Trial Outcomes & Findings for Perioperative Opioid-induced Hyperalgesia and Its Prevention With Ketamine and Methadone (NCT NCT01594047)
NCT ID: NCT01594047
Last Updated: 2025-10-01
Results Overview
Hyperalgesia is determined by stimulating with a won Fray hair N°16 along three lines at a right angle to the top, middle, and bottom sides of the surgical incision. Each line starts from the edge of the abdomen to the surgical incision. Stimulation continue from the edge toward the surgical incision until the patients reported a worsening in sensation The distance from the incision to where sensation change was measured. The mean of the three assessments was used as a measure of the extent of the hyperalgesia area.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
113 participants
Primary outcome timeframe
24 and 48 hours after surgery
Results posted on
2025-10-01
Participant Flow
Participant milestones
| Measure |
Zero/Morphine
Patient received a standard balance anaesthesia and morphine for post operative pain.
|
Ketamine/Morphine
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
|
Zero/Metadone
Methadone PCA
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
Ketamine/Methadone
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.).
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
29
|
30
|
27
|
27
|
|
Overall Study
COMPLETED
|
24
|
25
|
23
|
24
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
4
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Perioperative Opioid-induced Hyperalgesia and Its Prevention With Ketamine and Methadone
Baseline characteristics by cohort
| Measure |
Zero/Morphine
n=24 Participants
Patient received a standard balance anaesthesia and morphine for post operative pain.
|
Ketamine/Morphine
n=25 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
|
Zero/Metadone
n=23 Participants
Methadone PCA
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
Ketamine/Methadone
n=24 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.).
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
Total
n=96 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
58 years
n=5 Participants
|
60 years
n=7 Participants
|
57 years
n=5 Participants
|
57 years
n=4 Participants
|
58 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
63 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 24 and 48 hours after surgeryHyperalgesia is determined by stimulating with a won Fray hair N°16 along three lines at a right angle to the top, middle, and bottom sides of the surgical incision. Each line starts from the edge of the abdomen to the surgical incision. Stimulation continue from the edge toward the surgical incision until the patients reported a worsening in sensation The distance from the incision to where sensation change was measured. The mean of the three assessments was used as a measure of the extent of the hyperalgesia area.
Outcome measures
| Measure |
Zero/Morphine
n=24 Participants
Patient received a standard balance anaesthesia and morphine for post operative pain.
|
Ketamine/Morphine
n=25 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
|
Zero/Metadone
n=23 Participants
Methadone PCA
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
Ketamine/Methadone
n=24 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.).
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
|---|---|---|---|---|
|
the Extent of Hyperalgesia Area Proximal to Surgical Wound
24 hours
|
19.5 cm
Standard Deviation 12.76
|
14.68 cm
Standard Deviation 13.04
|
15.28 cm
Standard Deviation 12.72
|
11.04 cm
Standard Deviation 11.13
|
|
the Extent of Hyperalgesia Area Proximal to Surgical Wound
48 hours
|
16.04 cm
Standard Deviation 13.23
|
16.38 cm
Standard Deviation 14.05
|
18.09 cm
Standard Deviation 15.34
|
14.51 cm
Standard Deviation 12.75
|
SECONDARY outcome
Timeframe: 24 and 48 hours after surgeryPopulation: We performed a Dunn multiple comparison test for specific comparisons to assess group differences compared with the control group (0-Mo). Notably, the interaction term allowed us to test whether the effect of the two drugs, when jointly administered, was additive (lack of interaction) or more/ less than additive (presence of interaction). Data at 24 and 48 h were analyzed separately.
A Numerical Rating Scale (NRS) from 0 to 10 is used as a measure of pain intensity. Zero indicates the absence of any pain and 10 the worse pain never felt.
Outcome measures
| Measure |
Zero/Morphine
n=24 Participants
Patient received a standard balance anaesthesia and morphine for post operative pain.
|
Ketamine/Morphine
n=25 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
|
Zero/Metadone
n=23 Participants
Methadone PCA
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
Ketamine/Methadone
n=24 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.).
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
|---|---|---|---|---|
|
Pain Intensity Measured by a Numeric Rating Scale (NRS)
NRS static 24 hours
|
1.92 units on NRS
Standard Deviation 1.38
|
1.64 units on NRS
Standard Deviation 1.32
|
0.61 units on NRS
Standard Deviation 1.03
|
0.78 units on NRS
Standard Deviation 1.28
|
|
Pain Intensity Measured by a Numeric Rating Scale (NRS)
NRS dynamic 24 hours
|
4.75 units on NRS
Standard Deviation 1.80
|
4.68 units on NRS
Standard Deviation 1.95
|
3.13 units on NRS
Standard Deviation 2.20
|
3.04 units on NRS
Standard Deviation 1.66
|
|
Pain Intensity Measured by a Numeric Rating Scale (NRS)
NRS static 48 hours
|
1.36 units on NRS
Standard Deviation 1.92
|
0.88 units on NRS
Standard Deviation 1.13
|
0.87 units on NRS
Standard Deviation 1.36
|
0.5 units on NRS
Standard Deviation 0.88
|
|
Pain Intensity Measured by a Numeric Rating Scale (NRS)
NRS dynamic 48 hours
|
4.27 units on NRS
Standard Deviation 1.86
|
4.44 units on NRS
Standard Deviation 1.42
|
2.65 units on NRS
Standard Deviation 1.92
|
2.75 units on NRS
Standard Deviation 1.96
|
SECONDARY outcome
Timeframe: 48 hoursCumulative opioid consumption at 48 hours from surgery ( end of the study)
Outcome measures
| Measure |
Zero/Morphine
n=24 Participants
Patient received a standard balance anaesthesia and morphine for post operative pain.
|
Ketamine/Morphine
n=25 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
|
Zero/Metadone
n=23 Participants
Methadone PCA
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
Ketamine/Methadone
n=24 Participants
Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery.
Methadone administered by a PCA system (dose 2 mg, lock-out 12min.).
ketamine infusion: Ketamine infusion scheme: 5mcg/Kg/min from induction od anaesthesia for 10 min, than 2,5mcg/Kg/min for 20 min and than 2 mcg/Kg/min to the end of surgery
Methadone PCA: Methadone administered by a PCA system (dose 2 mg, lock-out 12min.)
|
|---|---|---|---|---|
|
Opioid Consumption
|
56.09 mg
Standard Deviation 28.99
|
66.9 mg
Standard Deviation 29.37
|
43.64 mg
Standard Deviation 20.24
|
38.96 mg
Standard Deviation 20.95
|
Adverse Events
Zero/Morphine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Ketamine/Morphine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Zero/Metadone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Ketamine/Methadone
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
Tognoli Emiliano MD
Fondazione IRCCS Istituto nazionale dei Tumori
Phone: +39 0223902282
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place