Efficacy of Silver Diamine Fluoride on Young Children With Severe Early Childhood Caries

Importance: Dental caries is a highly prevalent yet preventable disease affecting more than 40% of US children, with severe early childhood caries (S-ECC) leading to serious health and economic consequences. This randomized clinical trial addresses critical evidence gaps by evaluating 38% silver diamine fluoride (SDF) effectiveness for caries arrest in young US children with S-ECC to inform US Food and Drug Administration (FDA) regulatory approval. Objective: To assess the efficacy of 38% SDF vs placebo for arresting active cavitated dentin caries lesions in the primary dentition of US children with S-ECC. Design, Setting, and Participants: This phase III, multisite, randomized, blind, placebo-controlled clinical trial with 2 parallel arms had a data collection period from October 2018 through April 2023. Analyses were completed in 2024. Three sites recruited from and treated children in a variety of settings: medical and dental clinics, and Head Start and city/state-subsidized preschool programs. Enrolled participants included 830 generally healthy children aged 12 to 71 months with S-ECC and active cavitated lesions. Intervention: Children were randomized to receive either 38% SDF or placebo, applied at baseline and at 6 months. Clinical examinations were conducted at baseline, 3 months, 6 months, and 8 months. OUTCOMES AND MEASURES: The primary outcome was the proportion of arrested lesions at 6 months after 1 application. Secondary outcomes included arrest efficacy at 3 months and after 2 applications (8 months), and pain at or before 6 months and 8 months. Results: Of 830 enrolled children, 584 (70%) completed the study. Of those lost to follow-up (approximately 30%), 81 (9.8%) were lost due to COVID-19. Participants included 428 females (52%) and 402 males (48%) and were aged 1 to 6 years with high caries experience (mean [SD] decayed, missing, and filled teeth [dmft] (International Caries Detection and Assessment System ≥1), 11.36 [4.56]; range, 1-23). In intent-to-treat analyses, SDF arrested 57.5%, 54.0%, and 50.2% of lesions at 3 months, 6 months, and 8 months, respectively, vs placebo (18.8%, 22.5%, 17.4%, respectively). Differences (99.9% CI) in arrest rates were 38.7% (28.7%-48.6%), 31.5% (21.5%-41.6%), and 32.8% (22.3%-43.2%). There were no differences in pain. Averse events (AEs) were reported by 196 (47.3%) participants in the SDF group and 180 (43.3%) in the placebo group. Most AEs were mild to moderate in severity; 4 AEs (0.6%) were severe. Treatment-related AEs were similar between the 2 groups (SDF = 22.9%; placebo = 22.2%), as were discontinuation rates due to AEs (7.5% for both groups). Conclusion and Relevance: In this randomized clinical trial, 38% SDF was significantly more effective than placebo for arresting dentin caries lesions in primary teeth in young children with S-ECC, providing a noninvasive treatment for young high-risk children and supporting its consideration for FDA drug approval. Trial Registration: ClinicalTrials.gov Identifier: NCT03649659.