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.

总结