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: 9751647
• 负责人: Margherita R Fontana
• 金额: $ 349.83万
• 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/9751647
• 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; Exposure to; 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; 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; Placebos; Preparation; Prevention strategy; Primary Dentition; Procedures; Protocols documentation; Publishing; Quality of life; Randomized; Randomized Clinical Trials; 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; off-label use; oral care; pain reduction; prevent; primary outcome; recruit; 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 拟议的合作协议是为了支持III期随机临床试验（RCT）来评估 38％银氟（SDF）的有效性。 SDF最近在美国提供，并且无创， 廉价且易于使用用于治疗牙本质（即孔）牙齿的牙本病变的治疗。 幼儿汽车（ECC）仍然是美国儿童中最普遍的慢性病之一。也是 贫困儿童最常见的未满足的医疗保健需求之一（例如，刚起步的孩子）。如果允许进步 长时间未经治疗的疾病可能会带来广泛的牙齿​​，医疗，社会和生活质量后果。 ECC和重度ECC（例如，多发性腔病变或前牙中至少一个龋齿病变，在一个处发作 幼年的预防年龄相对便宜，但对儿童和家庭变得非常繁重，并且 治疗一旦病变的食物（例如，带有不锈钢冠，提取等）的治疗昂贵。在年轻人中尤其如此 需要广泛治疗或不合作和/或具有未成熟的认知功能，残疾或 医疗状况，在大多数情况下，在医院手术室的大多数情况下，在全身麻醉下进行治疗是 关心。 2016年，FDA向医疗保健提供者发出了通知，幼儿全身麻醉可能导致 永久性神经损害，应避免。那需要更好的策略来成功管理 幼儿的龋齿病变。拟议的RCT将通过针对入学的幼儿来完成 在临床上暴露于牙本质的汽车病变中，他们的头启动计划中的汽车病变。因为 SDF的突破疗法状态，FDA已大量参与该试验的设计，以确保它将达到 对龋齿病变“逮捕”毒品要求的要求，这在美国具有创新性 该申请已由Ind 124808的Advantage Silver Dental逮捕有限责任公司提交给FDA的一部分 我们的合作。在资金的头几个月中，我们将与NIDCR合作审查所有相关的研究文件和 RCT的手册，提交IRB并校准所有研究检查员。在本研究准备期之后， 经验丰富的研究团队将进行III期，多中心，随机，安慰剂对照的优势试验，并与 两个平行组涉及总共1,040名2-5岁的儿童，他们将在8个月的时间内受到关注 评估：牙齿-AIM 1（主要研究目的） - 38％SDF相隔两次，相隔6个月，被捕的造成的影响 初级牙列中的病变（使用ICDAS II严重性和活动标准评估）。次要目标将进一步 评估SDF的提供是否影响：Child-aim 2 [SDF对儿童疼痛和牙髓感染的影响]， 和家庭3 [SDF对口腔健康相关生活质量的影响（sub-aim 3a）以及治疗满意度和 可接受性（sub-aim 3b）]。这个创新项目的直接影响和意义是提供和 访问非侵入性，廉价且易于使用的替代策略来管理狂热的龋齿病变 获得护理机会有限的儿童可以通过逮捕病变，减轻疼痛，改善疼痛来深刻改善口腔健康 生活质量和大幅降低成本，所有这些都导致龋齿差异的大量降低。