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.
The University of Michigan, in collaboration with researchers at New York University, the University of Iowa, and Indiana University, are implementing a Phase III multicenter, randomized clinical trial (RCT), to test the effectiveness of 38% Silver Diamine Fluoride (SDF) in stopping the progression of cavities (i.e., large holes which result from dental caries, a common and debilitating disease) in the teeth of young children. Should the trial be successful, the impact would be a change in the standard of care and expanded access to a simple, non-invasive, inexpensive strategy to manage cavitated caries lesions in young children in the U.S., which otherwise are usually treated with potentially damaging general anesthesia and fillings or extractions. Access to this simple, non-aerosol treatment should result in a reduction of disparities in access to care, and improvements in oral health, which addresses the NIDCR Strategic Plan Goal 3 [to apply rigorous, multidisciplinary research approaches to overcome disparities in dental, oral, and craniofacial health].