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

项目摘要 拟议的相互竞争的延长项目要求获得更多时间的支持，特别是由于延误 与COVID-19大流行相关，以完成III期、多中心、随机、安慰剂对照 一项有两个平行组的试验，旨在评估38%银二胺氟化物（SDF）在美国不同人群中的有效性。 孩子SDF于2014年在美国用于治疗超敏反应，目前正在“关闭” 标签”用于空洞病变的管理。幼儿龋齿（ECC）仍然是最常见的龋齿之一。 美国儿童中普遍存在的慢性病。这也是最常见的未满足的医疗保健需求之一 服务不足的儿童。如果不加治疗，这种疾病可以有广泛的牙科，医疗，社会， 和生活质量的影响。严重的ECC是相对便宜的预防，但一旦病变空化它 治疗起来会变得非常麻烦和昂贵。这在需要治疗的幼儿中尤其如此。 广泛的治疗，在全身麻醉（GA）下治疗，在大多数情况下在医院手术 2016年，FDA发布通知称，GA在幼儿中可能导致 25因此，有效、可接受、廉价和侵入性较小的策略是 需要成功地管理幼儿的空洞龋病变。因为突破 根据SDF的治疗状态，FDA一直在积极参与这项试验的设计，以确保其符合 要求一个空洞龋齿病变“逮捕”药物索赔，这是创新的，在美国，和重要 促进执行。试验方案已由Advantage银Dental Arrest，LLC，保持器提交 IND 124808，作为我们正在进行的合作的一部分。在这段更新期间，我们经验丰富的 研究小组将继续招募，以达到1,144名1-5岁儿童的样本目标，这些儿童 严重ECC，将随访8个月以上。具体目标包括：评估38%可持续发展基金的影响 应用一次，以阻止6个月时乳牙列中临床暴露牙本质的空洞病变 随访（目标1，根据FDA），并在8个月随访时应用两次，间隔约6个月（目标2） [子目标2a将在3个月和6个月随访时比较一次应用的效果]。目标3将评估 38% SDF应用两次（间隔约6个月）对疼痛的影响[子目标3a将评估影响 单次应用后的疼痛（在3个月和6个月时评估）]。目标4将评估38%的SDF对 家庭水平结局[子目标4a]将评估对口腔健康相关生活质量的影响， 目标4 b：治疗满意度和可接受性]。这种创新的直接影响和意义 项目是，由此产生的数据可以导致一个空洞龋病变“逮捕”FDA的药物索赔SDF，这可以 通过支持实施有效、低成本的干预措施，深刻改善口腔健康， 随着时间的推移，确保有效性和安全性的监管，所有这些都有助于大幅减少 儿童龋齿。

PROJECT SUMMARY The proposed competing renewal project requests support for additional time, particularly due to delays associated with the COVID-19 pandemic, to complete a Phase III, multicenter, randomized, placebo-controlled trial, with two parallel groups, to assess the effectiveness of 38% silver diamine fluoride (SDF) in U.S. diverse children. SDF became available in the U.S. for treatment of hypersensitivity in 2014, and is being used “off label” for management of cavitated lesions. 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 underserved children. If allowed to progress untreated, the disease can have broad dental, medical, social, and quality of life consequences. Severe-ECC is relatively inexpensive to prevent, yet once lesions cavitate it becomes extremely burdensome and expensive to treat. This is especially true in young children who need extensive treatment, where treatment under general anesthesia (GA), in most cases in hospital operating rooms, is the standard of care.3 In 2016, the FDA issued a notice that GA in young children can result in permanent neurological damage.25 Thus, effective, acceptable, inexpensive and less-invasive strategies are needed to successfully manage cavitated caries lesions in young children. Because of the Breakthrough Therapy Status for SDF, the FDA has been heavily involved in the design of this trial to ensure it meets the requirements for a cavitated caries lesion “arrest” drug claim, which is innovative in the U.S., and important to facilitate implementation. The trial protocol has been submitted by Advantage Silver Dental Arrest, LLC, holder of IND 124808, to the FDA as part of our ongoing collaboration. During this renewal period, our experienced research team will continue enrollment to reach the sample target of 1,144 children, 1-5 years old, who have severe-ECC, and who will be followed over 8 months. Specific aims include to: Assess the impact of 38% SDF applied once, to arrest cavitated lesions that have exposed dentin clinically in the primary dentition at 6 month follow-up (Aim 1, per FDA), and applied twice, approximately 6 months apart, at 8 month follow-up (Aim 2) [Sub-Aim 2a will compare the effect of one application at 3- and 6-month follow-ups]. Aim 3 will assess the impact of 38% SDF applied twice, approximately 6 months apart, on pain [Sub Aim 3a will assess the impact on pain after a single application (assessed at 3 and 6 months)]. Aim 4 will assess the impact of 38% SDF on Family-Level Outcomes [Sub Aim 4a will assess the impact on Oral Health-Related Quality of Life, and Sub Aim 4b on Treatment Satisfaction and Acceptability]. The immediate impact and significance of this innovative project is that resulting data can lead to a cavitated caries lesion “arrest” FDA drug claim for SDF, which can profoundly improve oral health by supporting implementation of an effective, low-cost intervention, while ensuring regulation of efficacy and safety over time, all contributing to substantial reductions in disparities in caries in children.