Clinical trial NCT06690008: Fluoride Caries-control Effectiveness/Feasibility in Children
Official title: Comparison of the Effectiveness and Feasibility of Two Fluoride Therapies for Caries Management in Early Childhood: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Caries,Dental
Keywords: Dental caries
Fluorides
Diamine silver fluoride
Sodium fluoride
Prevention
Control
Lead sponsor: Universidad El Bosque, Bogotá
Sponsor class: OTHER
Collaborators: name: Corporacion Universitaria Rafael Nunez
name: Cooperative University of Colombia
First posted: 2024-11-15
Enrollment: 814
Sex: ALL
Minimum age (years): 3
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to two groups in parallel for the duration of the study
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare the effectiveness and feasibility of using silver diamine fluoride solution (SDF) vs. sodium fluoride varnish (NaF) for caries management in children from Bogotá (and its suburban areas) and Cartagena, in terms of: 1. Preventive effect: number of carious dental surfaces (cavitated); 2. Arrest effect: number of arrested carious tooth surfaces (cavitated); 3. Presence and number of adverse effects in soft/hard oral tissues.

Null hypothesis: Effectiveness and feasibility of silver diamine fluoride is superior to the sodium fluoride for caries management:

Alternative hypothesis: Effectiveness and feasibility of silver diamine fluoride is not superior to the sodium fluoride for caries management.

This Randomize Clinical Trial included 752 3-4 year-old medically healthy children from Bogotá and Cartagena. Participants were randomized equality distributed per city to receive either SDF (38%) or NaF (5%) biannually. Primary outcomes: cavity prevention and arresting effect. Secondary: feasibility (adherence, fidelity), dental-care parental satisfaction/acceptance and adverse effects. Data were analysed using t-tests, Chi-square, and Generalized estimating equations -GEE (0.05 statistical significance).

Detailed description: Ethical approval obtained from the Ethics Board at Universidad El Bosque (UEB 2022-11045).

It corresponds to a double-blind randomised controlled clinical trial following the Consolidated Standards of Reporting and Trials Checklist (CONSORT) 2010.

Population: 3-4-year-old children from (Bogotá and Cartagena) with good self-reported general health.

Sample size was calculated according to the protocols of Gao et al. and Chu et al. \[20,21\] (using Program-Sample-Size®, version 1.1), considering type-I error: 0.05; type-II error: 0.10; standard deviation: 0.87; expected average group-1: 0.47, group-2: 0.70. The determined sample size was of n=601, increasing due to possible losses by 25% (n=151) for a total sample size of n=752, equally divided in n=376 per arm (Bogotá/Cartagena).

Once the informed consent is signed by the parents, a comprehensive examination will be performed, including:

Ethical approval obtained from the Ethics Board at Universidad El Bosque (UEB 2022-11045).

Randomized, double blind, active controlled Clinical Trial. Population: 3-4-year-old children from (Bogotá and Cartagena) with good self-reported general health.

Sample size Sample size was calculated, according to the protocol of Gao et al. (2021) and Chu et al. (2002) (Program-Size-of-Sample®, version 1.1), considering type-I error: 0.05; type-II error: 0.10; standard deviation: 0.87; expected average group-1: 0.47, group-2: 0.70. Determined sample size: n=601, plus 25% (n=75) (dropout), for a total of: n=752, n=376/arm, evenly split (Bogotá/Cartagena).

Participants: In Cartagena and Bogotá (including surrounding areas), researchers invited children from private daycare centers, kindergartens associated with the Colombian Family Welfare Institute (ICBF), and charities to participate in a study. In 2022, they reached out to leaders of 12 centers in low-socioeconomic-status areas in Cartagena, and in 2022/2023, they contacted leaders of 37 centers in low and lower-middle socioeconomic areas in Bogotá. Ultimately, six centers in Cartagena and 32 in Bogotá agreed to participate, representing around 1,130 children.

On examination days, informed consent was obtained from the parents or guardians of 842 children aged 3-4 years (Cartagena: n=392; Bogotá: n=450). Exclusion criteria included children with systemic diseases, disabilities, regular medication use, unwillingness to participate, or families planning to move within the next year. Recruitment continued until the sample size was met. The study involved baseline and 1-year follow-up dental examinations.

Baseline and 1-year follow-up dental examinations: The dental assessments were conducted in community rooms using portable dental units, headlights, basic instruments (including a round-tip probe), and gauze/cotton rolls for drying. After children received assisted toothbrushing with 1450 ppm fluoride toothpaste, six calibrated examiners assessed caries using ICDAS visual criteria. Inter-examiner reproducibility (weighted Kappa: 0.71-0.80) and intra-examiner reproducibility (weighted Kappa: 0.75-0.92) were achieved.

Caries lesions were classified using the ICDAS-merged Epi criteria, which divides lesions by severity: Initial (non-cavitated, ICDAS 1-2), Moderate (microcavity or underlying shadow, ICDAS 3-4), and Extensive (cavity, ICDAS 5-6). Caries activity was determined through gentle probing: Active (soft or leathery dentine) or Inactive (shiny and hard dentine). Fillings and teeth missing due to caries were also recorded. This assessment was repeated at the 1-year follow-up, with intra-examiner reproducibility confirmed on 10% of assessments (weighted Kappa: 0.73-0.93 initially and 0.76-0.97 at follow-up).

Demographic characteristics and Oral health behaviors: At baseline, using previously established questionnaires, two research assistants conducted interviews with parents or caregivers to gather information on the children's socio-demographic characteristics (age, sex) and oral health-related practices. These included daily toothbrushing frequency, fluoride toothpaste use, daily consumption of free sugars, preventive dental care, and symptomatic-based dental visits.

Randomization: After the dental assessment in each city, children were randomly assigned to one of two intervention groups (NaF or SDF) by the coordinator using opaque, sequentially numbered envelopes in the presence of an external assistant. The randomization process followed the order of each child's arrival and was blind to the examiner. Stratified randomization was done at each site in a 1:1 ratio using Stata 14.0 software (Stata Corp, College Station, Texas USA). The randomization and allocation sequence were independently supervised by one of the authors.

Interventions: consisted of either sodium fluoride (NaF) or silver diamine fluoride (SDF), as determined by random assignment. In each city, two trained operators conducted the interventions per group. The NaF group received a 5% sodium fluoride varnish (Duraphat Varnish, Colgate-Palmolive, Germany), and the SDF group received a 38% silver diamine fluoride solution (Step 1 Riva Star - Southern Dental Industries (SDI) Limited, Australia), following the manufacturers' guidelines. Prior to treatment, parents and children were informed about possible staining of teeth and soft tissues, without disclosing group assignments.

During the intervention, operators assessed each child's behavior using Frankl's Behavior Rating Scale (Definitely Positive; Positive; Negative; Definitely Negative). Afterward, children self-assessed pain intensity using the Visual Analogue Face Scale, selecting one of five facial expressions (ranging from a smiling face for "Very light pain" to a crying face for "Unbearable pain").

Parents rated their satisfaction with the dental procedure on a 5-point Likert scale adapted from the Treatment Evaluation Inventory (TEI), with options from "Very satisfied" to "Very dissatisfied." At six months, the same intervention was repeated for each child by the same group of operators.

Adverse Effects: One day after the initial intervention and again at the 1-year follow-up, a trained examiner (blinded to the type of intervention) assessed the children for any adverse effects on soft tissues, specifically checking for irritation, inflammation, or pigmentation of the gums or mucous membranes.

Statistical Analysis: Clinical and demographic data, along with assessments of child behavior, pain, and parental satisfaction, were recorded digitally in a secure Microsoft Excel® (2010) database with limited access. The data were organized into a validated dataset and analyzed by an independent statistician using R version 4.3.1, with all tests two-tailed and a significance level of 0.05. Parametric tests were prioritized, but nonparametric methods were used for data that did not meet parametric assumptions, as determined by the Shapiro-Wilk test. Non-normally distributed variables were analyzed using the Mann-Whitney U test.

Participant demographics and clinical characteristics (city, sex, age), as well as oral health practices, adherence, fidelity, child behavior, pain, and parental satisfaction, were summarized using counts and percentages. Inter-examiner reproducibility for caries assessment was measured with a weighted kappa based on ICDAS criteria, maintaining a minimum kappa of 0.7, and intra-examiner reproducibility was assessed using the ICDAS-merged Epi criteria for consistency.

Caries experience (dmfs) was defined by 'decayed/cavity' (d) (ICDAS-merged Extensive caries), 'missing' (m), and 'filled' (f) tooth surfaces (s). Additionally, Initial and Moderate lesions were included in the ICDAS-merged Epi caries experience (ICDAS-merged Epi dmfs). At baseline, the proportion of subjects and the mean number (SD) of tooth surfaces with dmfs and ICDAS-merged Epi dmfs were calculated. Comparisons between children who remained in the study and those who exited early included the mean number (SD) of dmfs surfaces and five assessed oral health behaviors.

For binary outcomes, generalized linear models (GLMs) with a logit link were applied using R's glm function to calculate odds ratios, estimating the likelihood of new decayed surfaces between intervention and control groups. An odds ratio greater than 1 indicated a higher likelihood of decay in the intervention group, while an odds ratio less than 1 indicated a protective effect.

Chi-square tests assessed differences in child cooperation and parental satisfaction between groups, while adverse effects observed at 1-day and 1-year follow-ups were summarized with descriptive statistics. Both parametric and nonparametric tests were applied as appropriate to detect significant differences between treatment groups at each follow-up, with α = 0.05 set as the threshold for statistical significance.

Eligibility criteria: Inclusion Criteria:

* 3-4-year-old children (from Bogotá/Cartagena)
* Informed consent signed.
* Self-reported good general health (parents)

Exclusion criteria:

* Intention to move in the next 12 months
* Systemic disease, physical/mental disability
* Regularly medication intake
* Non-cooperative children

Primary outcomes:
measure: one-year proportion of children with new cavities and mean number of new cavities (preventive effect)
timeFrame: 12 months
measure: one-year proportion of children with inactive cavities and mean number of inactive cavities (arresting effect)
timeFrame: 12 months
Secondary outcomes:
measure: Feasibility at one year, in terms of adherence (number of participants recruited and retained)
timeFrame: 12 months
measure: Feasibility at one year, in terms of fidelity (number of participants not receiving a different intervention)
timeFrame: 12 months
measure: Number of participants with adverse oral soft tissue effects (one day after the first intervention and after one year)
timeFrame: 1 day and 12 months
measure: Satisfaction/acceptance of parents' children with caries care after the first intervention
timeFrame: 12 months
measure: Child's self-reported pain
timeFrame: After the dental intervention
measure: Child's behaviour (during the procedure)
timeFrame: During the dental intervention
Other outcomes:
Locations:
city: Bogotá
country: Colombia
facility: Universidad El Bosque
state: Bogotá DC
city: Cartagena
country: Colombia
facility: Corporación Universitaria Rafael Núñez
state: Bolivar
Study officials:
affiliation: Universidad El Bosq
name: Stefania Martignon, PhD
role: PRINCIPAL_INVESTIGATOR
References: