Department of Oral and Maxillo-Facial Surgery, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania -
Opera Contract Research Organization SRL, Timisoara, Romania.
Minerva Pediatr (Torino). 2023 Aug;75(4):514-527. doi: 10.23736/S2724-5276.18.05360-4. Epub 2018 Oct 4.
This study verified the feasibility of the monthly recruitment rate, tested the Face, Legs, Activity, Cry and Consolability Pain Assessment Tool (FLACC) for pain in infants and collected preliminary efficacy and safety data of a new proprietary oral gel formulation of high-molecular-weight hyaluronan (HMWHA) for the relief of teething. Results will support the design a future main trial vs. local anesthetic, that is currently the only clinically proven pain reliever.
This was a pilot, randomized, controlled, multicenter, open-label, and parallel-group trial. It was performed in two Romanian clinics recruiting infants from 3 to 36 months. Teething diagnosis was based on a minimum of three symptoms such as: local pain, swelling, erythema, hyper-salivation, and depth characteristics of unerupted tooth. Absence of subcutaneous mucosal laceration was also required. The children were assigned either to HMWHA (HABPX V 3.3, Bioplax Ltd, Wallington, UK), or to standard drug (Dentinox-Gel N; Dentinox, Berlin, Germany) and treated for 7 consecutive days. Investigators recorded the primary endpoints: swelling, redness and pain (by FLACC method), on days 0, 3 and 7. Changes in crying, mouth spasms, salivation, local pain, swelling, and redness were the secondary endpoints, recorded daily by the parents, on diary cards. Tolerability was assessed on day 14, too.
Twenty-seven Infants were allocated in HMWHA, and 30 in standard drug. Enrolment rate was 9 patients/month/site. A significant reduction for HMWHA group was evidenced in pain, swelling (from day 0 to 7, P=0.034 between groups), redness (from day 0 to 3, P=0.045 and from day 0 to 7, P<0.001 between groups) and confirmed by the parents' diary records. Pain measurements obtained by FLACC method are consistent with the data belonging to other parameters. Investigator's global assessment of performance was in favor of the HMWHA (P<0.005). Only two patients, both belonging to standard drug group, experienced adverse events (fever, not related to treatment) and dropped out of the study.
The results solve the feasibility questions and clearly evidence the performance of HABPX V 3.3 in teething symptoms, exceeding the objectives of a simple pilot trial to some extent. Coating oral gels containing HMWHA could be a therapeutic solution for both parents and physicians in managing the irritation and pain resulting from tooth eruption in children.
本研究验证了月度招募率的可行性，测试了用于评估婴儿疼痛的面部、腿部、活动、哭泣和安抚（FLACC）评估工具，并收集了一种新型高相对分子质量透明质酸钠（HMWHA）口腔凝胶制剂用于缓解出牙疼痛的初步疗效和安全性数据。结果将支持设计一项针对局部麻醉剂的未来主要试验，局部麻醉剂目前是唯一经临床证实的止痛剂。
这是一项在罗马尼亚两家诊所进行的试点、随机、对照、多中心、开放标签和平行组试验。招募的婴儿年龄为 3 至 36 个月。出牙诊断基于至少三个症状，如局部疼痛、肿胀、红斑、唾液过多和未萌出牙的深度特征。还需要无皮下黏膜撕裂。儿童被分配到 HMWHA（HABPX V 3.3，Bioplax Ltd，Wallington，英国）或标准药物（Dentinox-Gel N；Dentinox，Berlin，德国）组，并连续治疗 7 天。研究人员记录了主要终点：肿胀、发红和疼痛（采用 FLACC 方法），在第 0、3 和 7 天。次要终点为父母每日记录的哭泣、口痉挛、流涎、局部疼痛、肿胀和发红的变化。在第 14 天还评估了耐受性。
27 名婴儿被分配到 HMWHA 组，30 名婴儿被分配到标准药物组。每月每个地点招募 9 名患者。HMWHA 组在疼痛、肿胀（从第 0 天到第 7 天，组间 P=0.034）、发红（从第 0 天到第 3 天，P=0.045，从第 0 天到第 7 天，P<0.001 组间）方面的显著降低得到了证实，并且也得到了父母日记记录的证实。采用 FLACC 方法获得的疼痛测量值与其他参数的数据一致。研究者对疗效的总体评估有利于 HMWHA（P<0.005）。只有两名患者（均属于标准药物组）出现不良反应（发热，与治疗无关）并退出研究。
结果解决了可行性问题，并在一定程度上清楚地证明了 HABPX V 3.3 在出牙症状方面的表现，超出了简单试点试验的目标。含有 HMWHA 的口腔凝胶涂层可能为父母和医生在管理儿童出牙引起的刺激和疼痛方面提供一种治疗解决方案。
