臨床研究等提出・公開システム

Effect of Opioid Titration protocol using nociception monitors in gynecologic laparoscopic surgery with total hysterectomy: a Randomized Controlled Trial
(OPTIMIST-h study)

OPTIMIST-h study (OPTIMIST-h study)

75

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 (%)). NOL group (n=27) / HFVI group (n=23) / Control group (n=23) Patient characteristics Age (years) 46.3 (6.4) / 48.7 (7.3) / 48.0 (7.1) Weight (kg) 58.0 (9.0) / 57.3 (9.2) / 60.4 (11.9) Height (cm) 159.1 (5.0) / 158.8 (3.6) / 159.0 (4.5) BMI (kg/m^2) 23.0 (3.7) / 22.7 (3.7) / 23.9 (4.4) ASA-PS, n (%) I: 16 (59.3) / 10 (43.5) / 10 (43.5), II: 11 (40.7) / 13 (56.5) / 13 (56.5) Surgical data Procedure, n (%) Laparoscopic: 18 (66.7) / 16 (69.6) / 17 (73.9) Robot-assisted: 11 (40.7) / 7 (30.4) / 6 (26.1) Duration of surgery (min): 161.6 (38.1) / 162.2 (37.4) / 147.8 (30.6) Duration of anesthesia (min): 217.5 (38.4) / 217.6 (38.2) / 203.3 (33.8)

2024/MAR /25: Date of first participant enrollment 2025/DEC/25: Date of last visit A total of 100 potential study participants were recruited, 25 who did not meet eligibility criteria were excluded, and 54 were randomly assigned to a treatment group (intervention group 1 [NOL group], intervention group 2 [HFVI group], or control group [Control group]). One participant in the HFVI group and one in the control group discontinued participation, resulting in a final total of 73 participants (25 in the NOL group, 23 in the HFVI group, and 23 in the control group) for the main analysis.

No serious or causally related to the study adverse events (AEs) occurred in this study.

Analyses were conducted on the FAS (73 participants; 27 in the NOL group, 23 in the HFVI group, and 23 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 or HFVI group) - control group, and the mean and 95% confidence interval (CI) and p-value are estimated. Regarding the primary endpoints, confidence intervals adjusted for multiplicity (97.5% CI) will also be estimated. Primary endpoint Intraoperative remifentanil flowrate (mcg/kg/min) was 0.18 (0.06) in the NOL group, 0.22(0.10) in the HFVI group, and 0.20(0.07) in the Control group, respectively. Group differences were as follows: NOL-Control: -0.020 [97.5%CI, -0.064 to 0.024; 95%CI, -0.058 to 0.018; p=0.3026] HFVI - Control: 0.019 [97.5%CI, -0.038 to 0.077; 95%CI, -0.031 to 0.069; p=0.4417] Secondary endpoints 1) Comparison of biomarker values (IL-6, CRP, cortisol) between the three groups POD: post-operative day IL-6 Pre: NOL 1.6 (1.5) / HFVI: 2.2 (4.6) / Control: 2.0 (4.1) Post: NOL: 36.0 (32.3) / HFVI: 36.2 (32.9) / Control: 27.5 (19.0) Group differences in the Post NOL-Control: 8.5 [-6.9 to 23.9; p=0.2719] HFVI-Control: 8.8 [-7.2 to 24.7; p=0.2749] CRP Pre: NOL: 0.06 (0.06) / HFVI: 0.04 (0.05) / Control: 0.12 (0.17) POD1: NOL: 2.75 (2.15) / HFVI: 2.39 (1.45) / Control: 2.08 (1.15) POD 3: NOL: 3.70 (4.41) / HFVI: 4.43 (3.75) / Control: 3.76 (3.35) Group differences in the POD1 NOL-Control: 0.66 [-0.34 to 1.67; p=0.1916] HFVI-Control: 0.31 [-0.47 to 1.08; p=0.4326] Group differences in the POD3 NOL-Control: -0.06 [-2.31 to 2.20; p=0.9610] HFVI-Control: 0.67 [-1.442 to 2.78; p=0.5240] Cortisol Pre: NOL: 12.2 (6.0) / HFVI: 12.0 (5.2) / Control: 10.6 (4.2) Post: NOL: 12.6 (9.3) / HFVI: 7.0 (7.3) / Control: 6.3 (7.8) Group differences in the Post NOL-Control: 6.3 [1.4 to 11.2; p=0.0131] HFVI-Control: 0.7 [-3.8 to 5.2; p=0.7540] 2) Total amount of remifentanil administered during surgery Total amount of remifentanil (mcg/kg) was 10.17 (3.63) in the NOL group, 12.34 (5.52) in the HFVI group, and 11.19 (3.81) in the Control group, respectively. Group differences were as follows: NOL-Control: -1.02 [-3.14 to 1.10; p=0.3377] HFVI-Control: 1.15 [-1.67 to 3.97; p=0.4155] 3) Change in Quality of Recovery Score-15 values on the day before surgery (Pre), postoperative day (POD) 1 and 2. The Quality of Recovery Score-15 (QoR-15) values at each time point and the differences between groups were as follows. Pre: NOL 142.8 (10.1) / HFVI 143.7 (5.8) / Control 140.6 (10.8) POD1: NOL 108.7 (31.9) / HFVI 100.6 (28.6) / Control 104.0 (24.9) POD2: NOL 125.3 (20.1) / HFVI 123.9 (16.7) / Control 125.9 (18.7) Group differences in the POD1 NOL-Control: 4.7 [-11.8 to 21.2; p=0.5664] HFVI-Control: -0.6 [-11.7 to 10.5; p=0.9169] Group differences in the POD 2 NOL-Control: -3.4 [-19.4 to 12.5; p=0.6659] HFVI-Control: -2.0 [-12.5 to 8.5; p=0.7041] 4) NRS (Numerical Rating Scale) values on the day of surgery (2 hours postoperatively), at postoperative day (POD) 1, 2, 3, and at 3 months after surgery At rest 2 hours postoperatively: NOL 2.78 (2.06) / HFVI 2.57 (2.17) / Control 3.57 (2.09) POD1: NOL 1.33 (1.36) / HFVI 1.43 (1.70) / Control 1.39 (1.27) POD2: NOL 1.37 (1.47) / HFVI 1.00 (0.95) / Control 1.43 (1.44) POD3: NOL 0.59 (0.84) / HFVI 1.00 (1.31) / Control 0.91 (1.12) 3 months after surgery: NOL 0.07 (0.38) / HFVI 0.00 (0.00) / Control 0.13 (0.63) Group differences in the 2 hours postoperatively NOL-Control: -0.79 [-1.97 to 0.40; p=0.1870] HFVI-Control: -1.00 [-2.26 to 0.26; p=0.1182] Group differences in the POD1 NOL-Control: -0.06 [-0.81 to 0.69; p=0.8775] HFVI-Control: 0.04 [-0.85 to 0.94; p=0.9222] Group differences in the POD 2 NOL-Control: -0.06 [-0.90 to 0.77; p=0.8769] HFVI-Control: -0.43 [-1.16 to 0.29; p=0.2339] Group differences in the POD 3 NOL-Control: -0.32 [-0.88 to 0.24; p=0.2561] HFVI-Control: 0.09 [-0.64 to 0.81; p=0.8106] Group differences in the 3 months after surgery NOL-Control: -0.06 [-0.35 to 0.23; p=0.6984] HFVI-Control: -0.13 [-0.40 to 0.14; p=0.3338] On movement 2 hours postoperatively: NOL 4.30 (2.07) / HFVI: 3.45 (2.20) / Control: 4.77 (2.45) POD1: NOL 3.52 (2.05) / HFVI 2.96 (2.08) / Control 3.13 (1.71) POD2: NOL 3.70 (1.30) / HFVI 2.35 (1.61) / Control 3.17 (2.27) POD: NOL 2.41 (1.37) / HFVI 2.17 (1.40) / Control 2.74 (1.63) 3 months after surgery: NOL 0.15 (0.60) / HFVI 0.27 (0.70) / Control 0.26 (0.75) Group differences in the 2 hours postoperatively NOL-Control: -0.48 [-1.78 to 0.82; p=0.4642] HFVI-Control: -1.32 [-2.73 to 0.10; p=0.0672] Group differences in the POD1 NOL-Control: 0.39 [-0.70 to 1.47; p=0.4752] HFVI-Control: -0.17 [-1.31 to 0.96; p=0.7583] Group differences in the POD2 NOL-Control: 0.53 [-0.50 to 0.27; p=0.3070] HFVI-Control: -0.83 [-2.00 to 0.34; p=0.1618] Group differences in the POD 3 NOL-Control: -0.33 [-1.18 to 0.52; p=0.4374] HFVI-Control: -0.57 [-1.47 to 0.34; p=0.2141] Group differences in the 3 months after surgery NOL-Control: -0.11 [-0.50 to 0.27; p=0.5587] HFVI-Control: 0.01 [-0.43 to 0.45; p=0.7281] 5) Perioperative opioid (fentanyl) consumption Perioperative opioid use (mcg) was 478.97 (148.45) in the NOL group, 435.79 (142.15) in the HFVI group, and 453.18 (146.11) in the Control group, respectively. Group differences were as follows: NOL-Control: 25.78 [-58.30 to 109.90; p=0.5404] HFVI-Control: -17.39 [-103.10 to 68.27; p=0.6844] 6) Presence of chronic postsurgical pain There were 2 (2/27, 7.4%) in the NOL group, 4 (4/22, 18.2%; 1 missing) in the HFVI group, and 3 (3/23, 13.0%) in the Control group who had chronic postsurgical pain (NOL vs Control, p=0.5079; HFVI vs Control, p=0.6345).

This trial provides the first evaluation of NoL and HFVI within the same randomized study setting. Intraoperative remifentanil use was similar across all groups, and secondary outcomes also showed no meaningful differences in robot-assisted or laparoscopic hysterectomy.

May. 31, 2026

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/jRCTs052230195

Sasaki Yuka

Nara Medical University Hospital

840 Shijo-Cho, Kashihara, Nara

yukaa0810@naramed-u.ac.jp

Sasaki Yuka

Nara Medical University Hospital

840 Shijo-Cho, Kashihara, Nara

+81-744-22-3051

yukaa0810@naramed-u.ac.jp

Complete

Mar. 08, 2024

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

1) Female patients undergoing laparoscopic or robotic-assisted laparoscopic total hysterectomy
2) Patients classified as American Society of Anesthesiologists physical status 1-2
3) Patients between the ages of 20 and 85 years
4) Patients who have given written consent to participate in the study

1) Patients who are scheduled to undergo emergency surgery
2) Patients who are being treated with a beta-blocker (oral intake or patch)
3) Patients being treated with steroids
4) Patients who cannot secure the measurement site due to amputated fingers or nail lesions
5) Patients with a pacemaker
6) Patients after heart transplantation
7) Patients using drugs that affect sinus node (atropine, anticholinergic drugs)
(8) Patients who are incapable of consenting
9) Patients who are judged to be inappropriate as research subjects by the investigators responsible for the study.

Female

requiring hysterectomy

Intervention 1) The management protocol based on the Nociception Level (NoL) index calculated using PMD-200 (not approved in Japan) and the BIS monitor.
Intervention 2) The management protocol based on HFVI and PSI.

Hysterectomy

Hysterectomy

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 three groups
2) Total amount of remifentanil administered during surgery
3) Change in Quality of Recovery Score-15 values on the day before surgery(Pre), postoperative day (POD) 1 and 2.
4) NRS (Numerical Rating Scale) values on the day of surgery (2 hours postoperatively), at POD1, 2, 3 , and at 3 months after surgery
5) Perioperative opioid (fentanyl) consumption
6) Presence of chronic postsurgical pain

+81-744-29-8835

Feb. 26, 2024

none