Nedeljkovic Srdjan S, Correll Darin J, Bao Xiaodong, Zamor Natacha, Zeballos Jose L, Zhang Yi, Young Mark J, Ledley Johanna, Sorace Jessica, Eng Kristen, Hamsher Carlyle P, Maniam Rajivan, Chin Jonathan W, Tsui Becky, Cho Sunyoung, Lee Doo H
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
BMJ Open. 2017 Feb 17;7(2):e011035. doi: 10.1136/bmjopen-2016-011035.
In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery.
Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships.
Ethical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions. Trial results will be disseminated through scientific conference presentations and by publication in scientific journals.
NCT02489526; pre-results.
尽管在认识和技术方面取得了进展，但仍有相当数量的患者术后疼痛未得到有效治疗。在结直肠手术中，开发新型镇痛药尤为重要。肠道手术后的患者需要评估肠道功能的快速恢复情况，而阿片类药物会加重肠梗阻、恶心和便秘。我们描述了一项前瞻性、双盲、平行组、安慰剂对照的随机对照试验，以检验一种新型镇痛药VVZ -149在接受腹腔镜结直肠手术的成年人中，与单独使用阿片类镇痛药相比，在改善疼痛方面是否安全有效这一假设。
根据主要结局的样本量计算，我们计划招募120名参与者。将招募无重大内科合并症或正在使用阿片类药物且正在接受腹腔镜结直肠手术的成年患者。参与者在术后随机分配接受VVZ-149联合静脉注射（IV）氢吗啡酮患者自控镇痛（PCA）或对照干预（仅IV PCA）。主要结局是给药后8小时的疼痛强度差异总和（SPID-8 postdose）。参与者术后接受VVZ-149治疗8小时至主要研究终点，之后继续评估长达24小时。我们测量阿片类药物的消耗量，记录疼痛强度和疼痛缓解程度，并评估急救剂量的数量和阿片类药物的需求。为评估安全性，我们在给予研究药物后记录镇静、恶心和呕吐、呼吸抑制、实验室检查和心电图读数。我们评估镇痛反应的可能混杂因素, 如焦虑、抑郁和灾难化行为。该研究还将收集血样数据并评估药代动力学和药效学关系。
该研究方案已获得参与机构的机构审查委员会的伦理批准。试验结果将通过在科学会议上发表演讲和在科学期刊上发表来传播。
NCT02489526；预结果。
