Phase III RCT of the Effectiveness of Silver Diamine Fluoride in Arresting Cavitated Caries Lesions

氟化二胺银阻止空洞龋损有效性的 III 期随机对照试验

• 批准号: 9426625
• 负责人: Margherita R Fontana
• 金额: $ 202.72万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9426625
• 关键词: 5 year old; Address; Age; Agreement; Anterior; Biological; Calibration; Caring; Case Report Form; Child; Chronic; Clinical; Clinical Trials; Collaborations; Consent Forms; Country; Dental; Dental caries; Dental crowns; Dentin; Development; Devices; Diamines; Disease; Documentation; Drug Approval; Economics; Effectiveness; Enrollment; Ensure; Event; Experimental Designs; Family; Fluoride Varnishes; Fluorides; Funding; General Anesthesia; Goals; Government; Head Start Program; Health; Health Personnel; Health Services Accessibility; Healthcare; Hong Kong; Hospitals; Hypersensitivity; Improve Access; Indiana; Infection; Institutional Review Boards; Interdisciplinary Study; Iowa; Label; Lesion; Life; Manuals; Maryland; Medical; Methods; Michigan; Modeling; Monitor; NIH Program Announcements; National Institute of Dental and Craniofacial Research; Nervous System Trauma; New York; Operating Rooms; Oral; Oral health; Pain; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Preparation; Prevention strategy; Primary Dentition; Procedures; Protocols documentation; Publishing; Quality of life; Randomized; Randomized Clinical Trials; Recruitment Activity; Research; Research Personnel; Safety; Schedule; Secure; Severities; Silver; Site; Stainless Steel; Strategic Planning; Symptoms; Testing; Time; Tooth structure; Toothache; Training; U-Series Cooperative Agreements; Universities; Visual; White Spots; Work; chemical resource; clinical efficacy; cognitive function; cohort; cost; cost effective; craniofacial; data management; deciduous tooth; design; disability; disparity reduction; early childhood; effectiveness clinical trial; experience; health related quality of life; improved; innovation; multidisciplinary; oral care; prevent; primary outcome; satisfaction; screening; sex; social; standard of care; trial design

Summary The proposed Cooperative Agreement is for support for a Phase III randomized clinical trial (RCT) to assess the effectiveness of 38% silver diamine fluoride (SDF). SDF recently became available in the U.S., and is non-invasive, inexpensive and simple to use for management of cavitated lesions exposing dentin clinically (i.e., holes) in primary teeth. Early childhood caries (ECC) continues to be one of the most prevalent chronic conditions among U.S. children. It also is one of the most common unmet healthcare needs of poor children (e.g., Head Start children). If allowed to progress untreated for long periods of time, the disease can have broad dental, medical, social, and quality of life consequences. ECC and severe-ECC (e.g., multiple cavitated lesions or at least one caries lesion in the anterior teeth, with onset at an early age) is relatively inexpensive to prevent, yet becomes extremely burdensome on the children and families, and expensive to treat once lesions cavitate (e.g., with stainless steel crowns, extractions, etc.). This is especially true in young children who need extensive treatment, or are uncooperative and/or have immature cognitive functioning, disabilities, or medical conditions, where treatment under general anesthesia, in most cases in hospital operating rooms, is the standard of care. In 2016, the FDA issued a notice to health care providers that general anesthesia in young children can result in permanent neurological damage and should be avoided. Thus, better strategies are needed to successfully manage cavitated caries lesions in young children. The proposed RCT will be accomplished by targeting young children enrolled in Head Start programs who have cavitated caries lesions that have exposed dentin clinically. Because of the Breakthrough Therapy Status for SDF, FDA has been heavily involved in the design of this trial to ensure it will meet the requirements for a cavitated caries lesion “arrest” drug claim, which is innovative in the U.S. The proposed protocol in this application has been submitted by Advantage Silver Dental Arrest, LLC, holder of IND 124808, to the FDA as part of our collaboration. In the first months of funding, we will work with NIDCR to review all relevant study documents and manuals for the RCT, submit to IRBs, and calibrate all study examiners. Following this study preparation period, an experienced research team will conduct a Phase III, multicenter, randomized, placebo-controlled superiority trial, with two parallel groups involving a total of 1,040 children, 2-5 years old, who will be followed over a period of 8 months, to assess: The tooth-Aim 1 (Primary study aim)- the impact of 38% SDF applied twice, 6 months apart, on arrest of cavitated lesions in the primary dentition (assessed using the ICDAS II severity and activity criteria). Secondary aims will further assess whether the provision of SDF impacts: the child-Aim 2 [effects of SDF on children's pain and pulpal infection], and the family-Aim 3 [effects of SDF on oral health-related quality of life (Sub-Aim 3a), and treatment satisfaction and acceptability (Sub-Aim 3b)]. The immediate impact and significance of this innovative project is that provision of and access to a non-invasive, inexpensive, and simple to use alternative strategy to manage cavitated caries lesions for children with limited access to care could profoundly improve oral health by arresting lesions, reducing pain, improving quality of life, and significantly reducing costs, all contributing to substantial reductions in disparities in caries.

概括 拟议的合作协议旨在支持 III 期随机临床试验 (RCT)，以评估 38% 二胺氟化银 (SDF) 的功效最近在美国上市，并且是非侵入性的。 价格便宜且易于使用，用于治疗临床上乳牙中的牙本质空洞暴露病变（即孔洞）。 儿童早期龋齿 (ECC) 仍然是美国儿童中最常见的慢性疾病之一。 贫困儿童最常见的未满足的医疗保健需求之一（例如，如果允许进步的话，启蒙儿童）。 如果长期不治疗，这种疾病可能会对牙科、医疗、社会和生活质量产生广泛的影响。 ECC 和严重 ECC（例如，前牙中存在多个空洞病变或至少一个龋齿病变，发病时间为 早年）的预防成本相对较低，但对儿童和家庭来说却造成极大的负担，并且 一旦病变出现空洞，治疗费用昂贵（例如，使用不锈钢牙冠、拔牙等），这在年轻人中尤其如此。 需要广泛治疗、不合作和/或认知功能不成熟、残疾或 医疗条件下，全身麻醉治疗（大多数情况下是在医院手术室进行）是治疗的标准 2016 年，FDA 向医疗保健提供者发出通知，称幼儿全身麻醉可能会导致以下情况： 因此，需要更好的策略来成功管理。 幼儿中的空洞龋齿病变将通过针对入组的幼儿来完成。 在 Head Start 计划中，患有空洞性龋齿病变并在临床上暴露出牙本质的患者。 SDF 的突破性治疗状态，FDA 大力参与了该试验的设计，以确保其满足 对空洞龋齿病变“逮捕”药物声明的要求，这在美国是创新的。 该申请已由 IND 124808 持有者 Advantage Silver Dental Arrest, LLC 提交给 FDA，作为 在资助的最初几个月，我们将与 NIDCR 合作审查所有相关的研究文件和 RCT 手册，提交给 IRB，并校准所有研究审查员。 经验丰富的研究团队将进行一项 III 期、多中心、随机、安慰剂对照的优效性试验， 两个平行组，共涉及 1,040 名 2 至 5 岁儿童，将对他们进行为期 8 个月的跟踪调查，以 评估：牙齿目标 1（主要研究目标）- 间隔 6 个月两次应用 38% SDF 对阻止空化的影响 乳牙列损伤（使用 ICDAS II 严重性和活动性标准进行评估）。 评估 SDF 的提供是否影响：儿童目标 2 [SDF 对儿童疼痛和牙髓感染的影响]， 和家庭目标 3 [SDF 对口腔健康相关生活质量的影响（子目标 3a）以及治疗满意度和 可接受性（子目标 3b）] 这个创新项目的直接影响和意义在于提供和 获得一种非侵入性、廉价且易于使用的替代策略来管理空洞龋病变 获得护理机会有限的儿童可以通过阻止病变、减轻疼痛、改善口腔健康来极大地改善口腔健康。 生活质量，并显着降低成本，所有这些都有助于大幅减少龋齿的差异。