Hasselgren Emma, Groes-Kofoed Nina, Falconer Henrik, Björne Håkan, Zach Diana, Hunde Daniel, Johansson Hemming, Asp Mihaela, Kannisto Päivi, Gupta Anil, Salehi Sahar
Department of Physiology and Pharmacology, Division of Anaesthesiology, Karolinska Institutet, Stockholm, Sweden, Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden, Department of Pelvic Cancer, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
Br J Anaesth. 2025 Mar;134(3):662-670. doi: 10.1016/j.bja.2024.10.015. Epub 2024 Nov 20.
In a previous phase II trial, intraperitoneal local anaesthetics shortened the time interval between surgery and adjuvant chemotherapy, an endpoint associated with improved survival in advanced ovarian cancer. Our objective was to test this in a phase III trial.
A double-blind, phase III parallel superiority trial was conducted at two university hospitals in Sweden, within a public and centralised healthcare system. Women >18 yr with advanced ovarian cancer scheduled for cytoreductive surgery, an ASA physical status of 1-3 with no speech/language issues, were eligible. Participants were randomly assigned using a central computerised system to receive either ropivacaine 0.2% or saline 0.9% (placebo) intraperitoneally during and after surgery. The primary endpoint was time to return to intended oncologic therapy (RIOT), analysed using t-test and linear regression adjusted for centre.
Of the 225 women randomised between August 2020 and December 2023 (ropivacaine n=113; placebo n=112), 175 were included in the modified intention-to-treat analysis (ropivacaine n=86; placebo n=89). Median age: ropivacaine group 64 yr (56-73 yr), placebo group: 66 yr (57-74 yr). The mean RIOT in the ropivacaine group was 26.5 days vs 25.8 days in the placebo group, with a mean difference of 0.7 days (-2.2 to 3.4 days; P=0.65). Per-protocol analysis of 166 women yielded similar results, mean difference of 0.5 days (-2.4 to 3.4 days; P=0.74) days. There were no differences in short-term recovery or postoperative morbidity.
Intraperitoneal local anaesthetic did not shorten the time to RIOT among women undergoing surgery for advanced ovarian cancer in this trial.
ClinicalTrials.gov (NCT04065009), European Union Clinical Trials Register (2019-003299-38/SE).
在之前的一项II期试验中，腹腔内局部麻醉剂缩短了手术与辅助化疗之间的时间间隔，这一终点与晚期卵巢癌生存率提高相关。我们的目标是在一项III期试验中对此进行验证。
在瑞典的两家大学医院，于公共集中式医疗系统内开展了一项双盲、III期平行优效性试验。年龄>18岁、计划进行肿瘤细胞减灭术、美国麻醉医师协会（ASA）身体状况评分为1 - 3且无言语/语言问题的晚期卵巢癌女性符合入选条件。参与者通过中央计算机系统随机分配，在手术期间及术后接受腹腔内注射0.2%罗哌卡因或0.9%生理盐水（安慰剂）。主要终点为恢复至预期肿瘤治疗的时间（RIOT），采用t检验及根据中心进行调整的线性回归分析。
在2020年8月至2023年12月期间随机分组的225名女性中（罗哌卡因组n = 113；安慰剂组n = 112），175名纳入了改良意向性分析（罗哌卡因组n = 86；安慰剂组n = 89）。中位年龄：罗哌卡因组64岁（56 - 73岁），安慰剂组66岁（57 - 74岁）。罗哌卡因组的平均RIOT为26.5天，而安慰剂组为25.8天，平均差值为0.7天（-2.2至3.4天；P = 0.65）。对166名女性进行的符合方案分析得出了类似结果，平均差值为0.5天（-2.4至3.4天；P = 0.74）。短期恢复或术后发病率无差异。
在本试验中，腹腔内局部麻醉剂并未缩短晚期卵巢癌手术女性的RIOT时间。
ClinicalTrials.gov（NCT04065009），欧盟临床试验注册库（2019 - 003299 - 38/SE）
