COVID-19: The Effectiveness of Silver Diamine Fluoride- Role in Reducing Health Disparities in Young Children(AdminSuppl)

COVID-19：氟化二胺银的有效性 - 在减少幼儿健康差异方面的作用(AdminSuppl)

• 批准号: 10225014
• 负责人: Margherita R Fontana
• 金额: $ 142.28万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225014
• 关键词: 5 year old; Address; Administrative Supplement; Age; Agreement; Anterior; Biological; COVID-19; COVID-19 pandemic; Calibration; Caring; Case Report Form; Child; Chronic; Clinical; Clinical Trials; Collaborations; Consent Forms; Country; Dental; Dental caries; Dentin; Development; Devices; Diamines; Disease; Documentation; Drug Approval; Economics; Effectiveness; Enrollment; Ensure; Event; Experimental Designs; Exposure to; Family; Fluoride Varnishes; Fluorides; General Anesthesia; Goals; Government; Head Start Program; Health; Health Personnel; Health Services Accessibility; Healthcare; Hospitals; Hypersensitivity; Improve Access; Indiana; Institutional Review Boards; Interdisciplinary Study; Iowa; Lesion; Life; Manuals; 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; Outcome; Pain; Participant; Pharmaceutical Preparations; Phase; Placebos; Preparation; Preschool Child; Prevention strategy; Procedures; Protocols documentation; Publishing; Quality of life; Randomized; Randomized Clinical Trials; Research; Research Personnel; Role; Safety; Schedule; Secure; Silver; Site; Strategic Planning; Symptoms; Testing; Time; Tooth structure; Training; U-Series Cooperative Agreements; Universities; White Spots; clinical efficacy; cohort; cost; cost effective; craniofacial; data management; deciduous tooth; design; disparity reduction; early childhood; effectiveness testing; experience; follow-up; health disparity; health related quality of life; improved; innovation; multidisciplinary; off-label use; oral care; pain reduction; prevent; primary outcome; recruit; satisfaction; screening; sex; social; standard of care; trial design

Summary The proposed Administrative Supplement is an addition to a Cooperative Agreement for support of a Phase III randomized clinical trial (RCT) to assess the effectiveness of 38% silver diamine fluoride (SDF). SDF became available in the U.S. in 2014, and is being used “off label” for management of cavitated lesions 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. This is especially true in young children who need extensive treatment, or are uncooperative, etc., 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. This RCT will be accomplished by targeting young children 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. Following a study preparation period, an experienced research team is conducting a Phase III, multicenter, randomized, placebo-controlled superiority trial, with two parallel groups involving a total of 1,144 children, 1-5 years old, who will be followed over a period of 8 months, to assess the impact of 38% SDF on: Aim 1 (Primary study aim)- arrest of cavitated lesions after one application, assessed at 6 months follow-up; Aim 2- arrest of cavitated lesions after being applied twice, 6 months apart, and compare the effect of one application at 3 and 6 months (Sub-Aim 2a); Aim 3- pain after being applied twice, 6 months apart, and after a single application (assessed at 3 and 6 months; Sub-Aim 3a); and Aim 4- Family-level outcomes, including oral health-related quality of life (Sub-Aim 4a), and treatment satisfaction and acceptability (Sub-Aim 4b). 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 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. This supplement request is meant to address some of the impacts that the COVID-19 pandemic has had on recruitment, follow-up and retention of study participants, and additional costs associated with being able to resume clinical activities and replace 132 children that will be out of the study window.

总结 拟议的行政补充是对合作协定的补充， 随机临床试验（RCT）评估38%银二胺氟化物（SDF）的有效性。SDF成为 2014年在美国上市，并被“标签外”用于治疗乳牙中的空洞病变。早期 儿童龋齿（ECC）仍然是美国儿童中最普遍的慢性病之一。它也是一个 贫困儿童最常见的未满足的医疗保健需求（例如，先声夺人儿童）。如果不治疗， 长期以来，这种疾病会对牙齿、医疗、社会和生活质量产生广泛的影响。ECC和 严重ECC（例如，前牙中的多个空洞病变或至少一个龋齿病变，在早期发病）， 预防相对便宜，但对儿童和家庭造成极大负担，治疗费用昂贵 一旦病变形成空洞。这在需要广泛治疗或不合作等的幼儿中尤其如此， 在那里，在全身麻醉下的治疗，在大多数情况下在医院手术室，是护理的标准。2016年 FDA向卫生保健提供者发出通知，幼儿全身麻醉可能导致永久性 神经损伤，应避免。因此，需要更好的策略来成功地管理空洞龋 幼儿的病变。这项随机对照试验将通过针对有龋洞病变的幼儿来完成 临床上暴露了牙本质由于SDF的突破性治疗地位，FDA一直积极参与 在本试验的设计，以确保它将符合要求的一个空洞龋病变“逮捕”药物索赔，这是 本申请中提出的方案已经由Advantage银Dental Arrest提交， LLC，IND 124808的保持器，作为我们合作的一部分。在研究准备期之后， 一个经验丰富的研究团队正在进行一项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1，144名1-5岁儿童，将在8个月内进行随访， 评估38% SDF对以下方面的影响：目标1（主要研究目标）-在一次应用后阻止空洞病变，在 6个月随访;目标2-在间隔6个月的两次应用后阻止空洞病变，并比较 在3个月和6个月时应用一次（子目标2a）;目标3-应用两次后（间隔6个月）和单次应用后疼痛 应用（在3个月和6个月时评估;子目标3a）;和目标4-家庭层面的结果，包括与口腔健康相关的结果 生活质量（子目标4a）和治疗满意度和可接受性（子目标4 b）。直接影响和 这一创新项目重要性在于提供和获得一种非侵入性的、廉价的和使用简单的 为护理机会有限的儿童提供治疗龋齿病变的替代方案可以极大地改善口腔状况 通过阻止病变、减轻疼痛、改善生活质量和显著降低成本来改善健康，所有这些都有助于 大大减少龋齿的差异。本补充请求旨在解决 COVID-19大流行对研究参与者的招募、随访和保留以及额外费用产生了影响 与能够恢复临床活动和替换132名将在研究窗口之外的儿童有关。