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Effect of NoL -Directed Analgesic management on opioid usage in Robot-assisted laparoscopic radical prostatectomy - a Randomized Controlled Trial - (NOLDOR study) (NOLDOR study)

NOLDOR study (NOLDOR study)

54

Baseline background characteristics and surgical data for the efficacy analysis population (participants in the study who had events only, Full Analysis Set; FAS) are shown below (summarized as mean (SD) or frequency (%)). Patient characteristics NOL group(n=25) Control group(n=25) Age(years) 68(6.6) 68(5.8) Weight(kg) 69.9(9.7) 64.7(8.6) Height(cm) 169.8(7.4) 166.5(4.6) BMI(kg/m2) 24.2(3.2) 23.3(2.8) ASA-PS, n(%) ASA1: 3(12.0) 3(12.0) ASA2: 21(84.0) 22(88.0) ASA3: 1(4.0) 0(0.0) Surgical data Procedure, n(%) Standard RARP 11(44.0)14(56.0) RS-RARP 14(56.0) 11(44.0) Duration of surgery (min) 261(78) 259(63) Duration of anesthesia (min) 317(79) 315(64)

2022/JUL/19: Date of first participant enrollment 2023/SEP/11: Date of last visit A total of 73 potential study participants were recruited, 19 who did not meet eligibility criteria were excluded, and 54 were randomly assigned to a treatment group (intervention group [NOL group] or control group [Control group]). Two participants in the intervention group and two in the control group discontinued participation, resulting in a final total of 50 participants (25 in the intervention group and 25 in the control group) for the main analysis.

No serious adverse events (AEs) occurred in this study. There was one AE (fingertip redness) that could not be ruled out as causally related to the study, but it was a non-serious and minor.

Analyses were conducted on the FAS (50 subjects; 25 in the intervention group and 25 in the control group). Data per group will be summarized as mean (standard deviation) or number (%). Differences between groups are determined for the intervention group (NOL group) - control group (Control group), and the mean and 95% confidence interval and p-value are estimated. [Primary endpoint] Intraoperative remifentanil flowrate (mcg/kg/min) was 0.12 (0.02) in the NOL group and 0.16 (0.05) in the Control group, with a group difference of -0.04 [-0.06 to -0.02, p=0.0007]. [Secondary endpoints] 1) Comparison of biomarker values (IL-6, CRP, cortisol) between the two groups *POD: post-operative day IL-6 NOL Control Group-difference Values Difference-from-pre Values Difference-from-pre pre 1.50(2.05) - 1.14(0.69) - - post 66.24(58.20) 64.73(58.17) 72.05(60.20) 70.92(60.29) -6.18[-39.87 to 27.51]p=0.7138 POD1 49.29(24.76) 47.79(24.91) 67.14(51.73) 66.00(51.50) -18.21[-41.22 to 4.79]p=0.1179 CRP NOL Control Group-difference Values Difference-from-pre Values Difference-from-pre pre 0.09(0.09) - 0.14(0.35) - - POD1 4.45(1.27) 4.36(1.25) 5.38(1.98) 5.24(1.83) -0.88[-1.77 to 0.01]p=0.0532 POD3 4.23(2.59) 4.14(2.59) 4.94(2.45) 4.80(2.37) -0.65[-2.06 to 0.76]p=0.3577 Cortisol NOL Control Group-difference Values Difference-from-pre Values Difference-from-pre pre 11.83(5.01) - 10.96(3.38) - - post 9.12(7.38) -2.71(8.14) 6.33(5.36) -4.64(6.25) 1.92[-2.21 to 6.05]p=0.3543 2) Changes in NoL values before and after events such as intubation, initiation of insufflation and re positioning in laparoscopic surgery pre- and post-intubation Both groups showed an increase in NOL values after intubation, but returned to pre-intubation levels within about 5 minutes. Peak NOL values were lower in the NOL group. pre- and post-insufflation No significant change in NOL values was observed in both groups due to the initiation of insufflation. NOL values were consistently lower in the NOL group. pre- and post-head down position No significant change in NOL values was observed in both groups due to the initiation of position change (head down). NOL values were consistently lower in the NOL group. 3) Numerical Rating Scale (NRS) values on the day of surgery (2 hours after surgery), 1, 2, 3, and 7 days after surgery, and 3 months after surgery *POD: post-operative day At rest NRS for pain NOL Control Group-difference 2 hours 2.44(1.92) 4.04(1.93) -1.60[-2.69 to -0.51]p=0.0050 POD1 1.20(1.22) 1.44(1.23) -0.24[-0.94 to 0.46]p=0.4922 POD2 1.20(0.82) 1.40(1.15) -0.20[-0.77 to 0.37]p=0.4829 POD3 0.64(0.91) 0.96(1.02) -0.32[-0.87 to 0.23]p=0.2469 POD7 0.44(1.16) 0.40(0.58) 0.04[-0.48 to 0.56]p=0.8778 3months 0.16(0.62) 0.48(1.19) -0.32[-0.86 to 0.22]p=0.2410 On movement NRS for pain NOL Control Group-difference 2hours 3.80(1.91) 5.80(1.91) -2.00[-3.09 to -0.91]p=0.0006 POD1 3.44(1.64) 4.64(1.68) -1.20[-2.14 to -0.26]p=0.0137 POD2 3.24(1.33) 4.60 (2.00) -1.36[-2.33 to -0.39]p=0.0068 POD3 2.36(1.19) 4.08 (1.53) -1.72[-2.50 to -0.94]p<0.0001 POD7 1.24(1.51) 1.72 (1.37) -0.48[-1.30 to 0.34]p=0.2446 3months 0.16(0.62) 0.48(1.19) -0.32[-0.86 to 0.22]p=0.2410 4) Perioperative opioid consumption Perioperative opioid use (requirement times) was 16.68(16.74) in the NOL group and 25.92(25.30) in the Control group, with a group difference of -9.24 [-21.44 to 2.96, p=0.1344]. 5) Presence of chronic postsurgical pain There were 2 (2/25, 8.0%) in the NOL group and 5 (5/25, 20.0%) in the Control group who had chronic postsurgical pain (p=0.2087).

NOL-directed analgesic management reduced remifentanil consumption by 20% and the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3 without an increase in inflammatory marker levels.

Mar. 31, 2025

June. 27, 2024

https://link.springer.com/article/10.1007/s00540-024-03365-x

No

IPD will not be shared, but a summary data required will be provided as needed for reasonable request.

https://jrct.mhlw.go.jp/latest-detail/jRCTs052220034

Tanaka Nobuhiro

Nara Medical University Hospital

840 Shijo-Cho, Kashihara, Nara

nobuhirotanaka@naramed-u.ac.jp

Tanaka Nobuhiro

Nara Medical University Hospital

840 Shijo-Cho, Kashihara, Nara

+81-744-22-3051

nobuhirotanaka@naramed-u.ac.jp

Complete

May. 27, 2022

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

1) Male patients undergoing scheduled robot-assisted laparoscopic radical prostatectomy
2) Patients who were classed as American societyof anesthesiologists performance status (ASA-PS)
1-3
3) Patients aged between 20 and 85 years old
4) Patients who have given written consent to participate in the study

1) Patients undergoing emergency surgery applied for the day
2) Patients taking beta-blockers, or applying patches for this drug
3) Patients taking oral steroids
4) Patients who cannot secure the measurement site due to a amputation of the finger or lesion on
the nail
5) Patients with inability to give consent
6) Patients who have been judged inappropriate in the study by the investigator or sub-investigator

Male

Prostate cancer

Use the analgesic protocol with a device not approved in Japan (PMD-200)

Amount of intraoperative remifentanil usage
(Total amount of remifentanil divided by the usagetime (min) and ideal body weight (kg) )

1) Comparison of biomarker values (IL-6, CRP, cortisol) between the two groups
2) Changes in NoL values before and after events such as intubation, initiation of insufflation and re positioning in laparoscopic surgery
3) Numerical Rating Scale (NRS) values on the day of surgery (2 hours after surgery), 1, 2, 3, and 7 days after surgery, and 3 months after surgery
4) Perioperative opioid consumption
5) Presence of chronic postsurgical pain

+81-744-29-8835

May. 19, 2022

none