Resin infiltration versus self-assembling peptide P11-4 with and without fluoride varnish for white spot lesions in children: a randomized controlled trial

Background: Comparative clinical evidence regarding minimally invasive protocols for non-cavitated white spot lesions (WSLs) in children remains limited. This trial compared resin infiltration (RI), self-assembling peptide P11-4 monotherapy, and P11-4 with 5%sodium fluoride varnish (P11-4 + FV) over 6 months. Methods: In this multicenter, single-masked, three-arm parallel randomized controlled trial, 105 children aged 7–14 years with non-cavitated WSLs (International Caries Detection and Assessment System (ICDAS II) score 2) on both maxillary central incisors were randomized at the patient level (35 per group; 210 teeth). The primary outcome was color change (∆E), assessed using CIE L*a*b* (CIELAB) photographic analysis; secondary outcomes were visual lesion regression (ICDAS II) and lesion activity measured using DIAGNOdent. Given baseline imbalance, prespecified baseline-adjusted analyses (linear mixed-effects models, analysis of covariance (ANCOVA), and rank-based ANCOVA) informed primary inference. Significance was set at p < 0.05. Results: Two hundred teeth were analyzed per protocol. After adjusting for baseline severity, between-group differences in color change were not significant (p = 0.094). RI produced the most rapid ICDAS II improvement (score 1.32, standard deviation (SD) 0.94, post-treatment). Because DIAGNOdent readings from infiltrated surfaces are confounded by the resin optical pathway, fluorescence comparisons were restricted to non-resin arms; at 6 months, P11-4 + FV was lower (mean 1.10, SD 0.94) than P11-4 monotherapy (mean 3.79, SD 3.26; p < 0.001), which showed a significant rebound. Conclusions: No significant between-group difference in color outcome remained after baseline adjustment; as the trial was not powered for equivalence, this reflects a non-detected rather than proven difference. RI provided the most rapid visual improvement, whereas P11-4 + FV showed the most durable reduction in lesion-activity fluorescence. Protocol selection should follow the primary goal: rapid esthetic correction (RI) or durable lesion-activity control (P11-4+ FV). Clinical Trial Registration: ClinicalTrials.gov NCT06708481 (prospectively registered, August 2024).

White spot lesion; Resin infiltration; Self-assembling peptide P11-4; Fluoride varnish; Randomized controlled trial; Remineralization

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