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: 10708266
• 负责人: Margherita R Fontana
• 金额: $ 93.3万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10708266
• 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; 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; Placebo Control; 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; effectiveness evaluation; effectiveness testing; 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.

总结 拟议的合作协议是为了支持III期随机临床试验（RCT），以评估 38%银二胺氟化物（SDF）的有效性。SDF最近在美国上市，并且是非侵入性的， 用于在临床上处理暴露牙本质的空穴损伤（即，牙齿上的洞。 幼儿龋齿（ECC）仍然是美国儿童中最普遍的慢性疾病之一。它也是 贫困儿童最常见的未满足的医疗保健需求之一（例如，先声夺人儿童）。如果允许发展 如果长期不治疗，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， 早期）预防起来相对便宜，但对儿童和家庭来说却变得极其沉重， 一旦病变形成空洞则治疗昂贵（例如，具有不锈钢牙冠、拔牙等）。尤其是年轻人 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，其中全身麻醉下的治疗，在大多数情况下在医院手术室，是标准的 在乎2016年，FDA向医疗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，需要更好的战略来成功地管理 幼儿的龋齿病变。拟议的随机对照试验将通过针对入学的幼儿来完成 在先声夺人计划谁有空洞龋病变，暴露牙本质临床。因为 SDF的突破性治疗状态，FDA一直在积极参与本试验的设计，以确保其符合 在美国，这是创新的。 本申请由Advantage银Dental Arrest，LLC（IND 124808的保持器持有者）提交给FDA，作为 我们的合作。在获得资助的头几个月，我们将与NIDCR合作，审查所有相关的研究文件， RCT手册，提交给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2-5岁儿童，他们将接受为期8个月的随访， 评估：牙齿-目标1（主要研究目标）-38% SDF应用两次（间隔6个月）对阻止空化的影响 乳牙列病变（使用ICDAS II严重程度和活动性标准评估）。次要目标将进一步 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（子目标3a）和治疗满意度的影响， 可接受性（子目标3b）。这一创新项目的直接影响和意义在于， 获得一种非侵入性的，廉价的，简单易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 生活质量，并大大降低成本，所有这些都有助于大幅度减少龋齿的差异。