Effectiveness, acceptability and oral health-related quality of life of silver diamine fluoride compared with atraumatic restorative treatment for the management of early childhood caries: protocol of a pragmatic randomised clinical trial

Abstract

Introduction

Early childhood caries (ECC) continues to be a public health problem. The application of silver diamine fluoride (SDF) is a simple, non-invasive procedure. This study aims to evaluate SDF’s effectiveness, acceptability and oral health-related quality of life (OHRQoL) compared with atraumatic restorative treatment in managing ECC.

Methods and analysis

An open-label parallel superiority randomised clinical trial will be conducted involving children aged 2–5 years. Participants will include children with at least one active cavitated lesion (ICDAS 5+) of their primary teeth, with no signs of pulp involvement. The trial will occur at preschools in the La Araucanía and Metropolitan Regions of Chile from 2025 to 2027. The primary outcome variable will be the caries lesion arrest, acceptability and OHRQoL. We will also determine the presence of any adverse effects. Evaluations will be carried out at 6 and 12 months. A sample of 234 teeth with carious lesions per group is estimated. The primary inferential analysis will be performed on an intention-to-treat basis; a per-protocol analysis will be conducted for adverse effects. For caries lesion arrest, a multilevel logistic regression model adjusted for significant covariates will be used to account for within-child clustering. The acceptability will be assessed through quantitative and qualitative methods. The magnitude of change in OHRQoL between baseline and follow-up will be quantified using effect size estimates derived from the early childhood health impact scale survey data.

Ethics and dissemination

This study’s implementation benefits the study population, and the ethical principles of research have been considered and approved by the Science Committee of the University, Resolution N°049_19. The results and conclusions of the clinical trial will be published in academic conferences and peer-reviewed journals.

Trial registration number

NCT06786975.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This is a parallel, cluster-randomised clinical trial of superiority, providing high-quality evidence in a real-world community setting.

• The trial compares non-invasive and minimally invasive treatments for the management of caries, applying rigorous and standardised international methodologies.

• Effectiveness will be assessed through patient-important outcomes, including caries lesion arrest and oral health-related quality of life.

• The study incorporates both quantitative and qualitative methods to evaluate acceptability and patient experience.

• Given the clinical characteristics of the interventions, neither participants nor examiners can be blinded to the allocated treatment, presenting a potential source of bias.

Introduction

Dental caries is the most common chronic non-communicable disease worldwide.¹ Although it can manifest at any stage of life, when it affects the primary teeth of children under 6, it is referred to as early childhood caries (ECC).1,3 Despite a decline in caries prevalence worldwide over recent decades, approximately 530 million children are affected by caries in their primary teeth.⁴ As a result, ECC poses a public health concern in specific populations, with challenges particularly pronounced in developing countries and among vulnerable groups in developed nations, where reported rates can reach as high as 90%.^{5 6} In Chile, the prevalence of (ECC) varies widely, ranging from 7.8% to 88%, depending on diagnostic criteria and the sociodemographic characteristics of the population.^{6 7}

The consequences of ECC extend beyond a child’s oral health, adversely compromising their quality of life by hindering cognitive development, growth, sociability and self-esteem, among other factors.8,10

Conventional dental treatment is largely surgical and often requires general anaesthesia due to the challenge of managing young children with limited cooperative behaviour.¹¹ However, general anaesthesia carries a high risk for children, a financial burden for families and an important cost for healthcare systems.⁹ Moreover, the frequent recurrence of carious lesions in traditional treatments, together with the inequitable accessibility and availability of conventional care in many countries, underscores the need for simple, cost-effective alternative treatments to mitigate the inequity and high prevalence of the disease.¹²

The American Academy of Paediatric Dentistry promotes an approach that involves managing caries as a chronic disease, along with active surveillance and minimal intervention.¹¹ Minimally invasive dentistry (MID) aims to manage carious lesions conservatively to preserve tooth structure.13,15 Evidence shows that MID effectively arrests the progression of dentine caries in primary teeth compared with conventional restorations.¹⁶

Current recommended treatments for cavitated carious lesions include the minimally invasive atraumatic restorative treatment (ART) and the non-invasive silver diamine fluoride (SDF).¹⁷

ART is a recommended intervention for children living in low- and middle-income countries where resources, treatment facilities and skilled labour are limited.¹⁸ The procedure involves the removal of demineralised dentine using only manual instruments, without the use of electrically powered equipment (such as turbines and micromotors), and does not require local anaesthesia. It is then followed by the closing of the cavity with glass ionomer cement. In contrast to conventional restorative techniques using rotary instruments, the main advantages of ART include the potential to conduct treatments outside the dental office, thereby reducing costs, and a biological method that requires minimal cavity preparation, preserving the tooth structure.¹⁹ In a 2017 Cochrane review, the authors concluded that ART may reduce pain during the procedure compared with conventional treatment (MD −0.65, 95% CI −1.38 to 0.07; 40 participants analysed).²⁰ The use of hand instruments minimises iatrogenic damage to the tooth, reducing the risk of endodontic treatment and possible tooth extraction.^{3 21} These advantages are especially important for populations in low- and middle-income countries, where access to dental care can be complicated. In a 2024 clinical trial, the arrest rate of ART was 87.2%, higher than those reported in previous studies.²²

In recent times, caries management using non-invasive treatments has gained significant traction worldwide. SDF with the molecular formula Ag(NH3)2F was approved by the US Food and Drug Administration in 2014. It inhibits demineralisation, stimulates tooth tissue remineralisation and arrests the progression of carious lesions.¹³

The specific interest in SDF centres around its five attributes: (1) control of pain and infection; (2) ease of application; (3) low material cost; (4) minimal human resource time and training and (5) non-invasive. In this sense, some authors refer to SDF as a possible agent to alter traditional approaches to caries prevention and monitoring.²³

SDF can be used outside the clinical setting, as it is easy to apply and does not necessarily require dental equipment for its application.²⁴ Additionally, it is a product that is well accepted even by young children as it can be applied without removing tooth tissue and without the use of manual or rotary instruments.²⁵ Therefore, the material is well suited for application in remote areas, schools, disadvantaged communities and dental offices. Countries, such as Argentina, Australia, Brazil, China and Japan, have implemented SDF-based programmes at the community level.²⁶

SDF is highly effective, with reported success rates ranging from 53% to 91% when applied two times a year.¹⁶ A meta-analysis confirms that, despite the heterogeneity of systematic reviews evaluating SDF among other techniques, it is effective in arresting caries progression in primary teeth compared with conventional methods.¹⁶ Unfortunately, the dark staining of the treated lesions is a significant barrier to the widespread acceptance of this treatment.²⁷ Other adverse effects reported in the literature are tooth or gum pain, inflammation and gingival whitening.²⁷

Although ART and SDF proved effective, it remains uncertain whether either treatment is more effective at arresting caries in primary teeth.²⁸ Additionally, there is still limited evidence regarding the acceptability and improvement of oral health-related quality of life (OHRQoL).²⁹

Evidence suggests that further research is necessary to ensure that recommendations are not based solely on clinical effectiveness but also include patient-reported outcome measures (PROMs) and the child’s experience and acceptability.¹⁶ PROMs and patient-reported experience measures (PREMs), such as quality of life, functional status, health status or satisfaction, are essential for assessing oral health status and evaluating the impact of dental care.³⁰ Evidence highlights the need to use approaches, such as PROMs and PREMs, in formulating oral health policies to facilitate decision making.³¹

In response, the study aims to evaluate the effectiveness, acceptability and OHRQoL of SDF compared with ART in managing ECC.

Methods

This pragmatic, open-label, multicentre, parallel, randomised clinical trial will be conducted from 2025 to 2027 in preschools affiliated with JUNJI and INTEGRA in Chile’s Araucanía and Metropolitan Regions. The population attending these schools is mainly of low socioeconomic level.32,34 This protocol report has followed the ‘Standard Protocol Items: Recommendations for Intervention Trial Guidelines’³⁵ and was registered at www.clinical-trials.gov (NCT06786975).

Participants, eligibility criteria

All children attending selected preschools will be invited to participate in this study. The inclusion criteria will be given as follows.

• Children aged 2–5 years and 11 months, for whom a parent or legal caregiver has provided written informed consent.

• According to the International Caries Detection and Assessment System, children with at least one active cavitated lesion (ICDAS 5+) on occlusal, smooth and/or proximal surfaces of primary dentition, as detected by visual and tactile examination.

The exclusion criteria will be as follows.

• Children with a severe underlying systemic disease or severe disability.

• Children with an allergy to the dental materials used (silver, latex or others).

• Children with temporary residence.

• Children with severe alterations in the dental structure.

• Children with ICDAS 6 carious lesions in molars and/or canines.

• Children with untreated oral conditions with PUFA (counts the number of teeth with pulp exposure (P/p), ulceration of the oral mucosa due to root fragments (U/u), fistula (F/f) and abscess (A/a)) index>=1.³⁶

Clinical examination

Before the treatments, parents/caregivers and preschool teachers will receive oral health education on the main caries risk factors (oral hygiene, diet and use of fluorides). The preschool teacher will brush the preschoolers’ teeth with fluoride toothpaste (1100 ppm) before the dental examination.

The examinations will be conducted in designated rooms at the schools under artificial light and with visual inspection of the oral cavity. Children will be examined three times: a previously trained investigator will perform a baseline examination before randomisation, then at 6 and 12 months. Oral hygiene will be assessed using the Greene–Vermillion simplified oral hygiene index without the use of a plaque-disclosing agent. The presence of carious lesions and pulp/abscess involvement will be established according to the ICDAS³⁷ and PUFA criteria,³⁶ respectively. Caries activity and cariogenic risk will be recorded according to the caries care guide.³⁷

Calibration of examiners for clinical examinations

Interventions will be performed by specialists in paediatric dentistry previously trained by experts in the ICDAS criteria. The calibration of the examiners will take place before the study, and it will be divided into two phases: (1) theoretical training on the study protocol, diagnostic criteria, preparation of clinical records, systematisation of the dental examination and resolution of doubts or discrepancies and (2) training on extracted teeth. The investigator will examine 36 extracted teeth (arranged in individual sockets) and apply the ICDAS diagnostic criteria to detect and assess carious lesions per tooth. The extracted teeth will be analysed two times, 1-week apart to determine the inter- and intraexaminer agreement level.

Description of the interventions

Intervention group (SDF)

The teeth will be isolated with cotton rolls and/or gauze. Caries lesions will be dried with cotton balls and/or a triple syringe. Gingival barrier will be applied to the marginal and interproximal gingiva surrounding the tooth. Every 6 months, a 38% SDF solution will be applied to carious lesions (ICDAS 5+) using a microbrush for 10-15 seconds, followed by the removal of excess solution with gauze. Finally, the preschool teacher will be informed that the child should refrain from eating, drinking or rinsing their mouth for the next 30 min.

Control group (ART)

All children in the control group will be treated according to the ART philosophy described by Frencken.¹⁸ The cavity will be filled with glass ionomer using a spatula (Ketac MolarTM, 3M ESPETM) in accordance with the manufacturer’s specifications. Digital pressure (with petroleum jelly) will be applied for a few seconds. A metal and celluloid band will be used for the occlusal-proximal and anterior-proximal caries lesions, respectively. Any excess will be removed using dental floss (before the material sets), and the occlusion will be assessed using articulating paper. Finally, petroleum jelly will be applied to safeguard the restoration following the preliminary adjustment (about 5 min).

Follow-up

Trained and calibrated investigators, who are blinded to the treatment interventions, will conduct the 6- and 12-month follow-up assessments using the same diagnostic criteria as those employed during the baseline examination. All outcome variables specified in the protocol will be evaluated.

The criteria for classifying active carious lesions will be based on the caries care guide.³⁷ For the SDF group, the criteria for coronal caries will be used. For the ART group, the criteria for caries associated with restorations and sealants will be applied, using the same stages as those considered for coronal caries. Still, the carious lesion is associated with a restoration or a sealant. Differentiation should be based on the status of the restoration: good margin integrity; defective (plaque retentive can be adapted) and defective (requires replacement).

Adverse effects, such as tooth or gum pain, inflammation or gingival whitening reported by parents/caregivers and/or educators, will be recorded in the clinical record and clinically monitored. In the event of any dental complication, such as an abscess, active fistula or crown fracture, the child will receive free treatment at the health centres of the participating institutions.

To improve treatment adherence, the child’s parent/caregiver will be contacted by telephone to remind them of the appointment. After the dental care, they will be given a printed and digital certificate indicating the intervention performed, postintervention care instructions and the next scheduled appointment.

Study participants can continue their hygiene and healthy eating routines at home and preschool. If the child has filled teeth from the carious lesions included in this study that were treated outside of it, those will be handled as missing data.

Primary outcome

• Arrest of the carious lesion: the lesion’s activity and inactivity will be assessed. The parameters described in the caries care guide³⁷ will be considered for assessing activity. For the SDF group, the lesion’s surface should have a shiny appearance and a hard consistency on examination to be considered inactive. When a soft, leathery and plaque-retentive tissue is present, the lesion will be considered active. For the ART group, the Caries-Associated to Restorations or Sealants (CARS) criteria will be applied.³⁸ A restoration will be considered inactive if the margin is intact (good margin). Conversely, on presentation of a restoration with plaque-retentive requirements that necessitate adjustment or replacement, it will be considered active.

• Parental acceptability (quantitative measure): it will be measured through a survey at 1-month, 6-months and 12-months post-treatment following a questionnaire of our own design.

• Parental acceptability (qualitative measure): a qualitative method will be used through semistructured interviews to be conducted 1 month after the intervention.

• Children’s acceptability: it will be assessed by the operator using Frankl’s scale³⁹ at the time of the intervention.

• Change in OHRQoL: it will be measured by the difference in the early childhood health impact scale (ECOHIS)⁴⁰ score between baseline and 6 months.

Secondary outcomes

• Absence of pulp pathology: measured with PUFA index.³⁶

• Presence of the tooth in the mouth: this indicates that the treated tooth is still present in the mouth during the follow-up examination and has not been surgically extracted.

• Presence of adverse effects: it will be collected through a questionnaire given to the parents/caregivers after the application of the interventions and in the check-ups at 6 and 12 months.

Study timeline

The study spans 30 months, comprising 3 months for calibration and coordination, 9 months for recruiting and implementing interventions, 12 months for follow-up to assess outcome variables and 6 months for analysis and submission for publication (online supplemental file 1).

Sample size

According to the literature, a caries arrest rate of 45% is expected among children in the SDF group. The sample size calculation was designed to detect the differences of at least 15% points between the two protocols in favour of the SDF protocol.⁴¹ Based on a significance level of 5% and a statistical power of 80%, it is possible to estimate that the minimum sufficient sample size is 195 teeth with carious lesions per group. Assuming an average of three teeth with carious lesions per child, an intragroup correlation coefficient of 0.1, as reported by Ruff et al,²⁰ and anticipating a loss to follow-up of 20%, a sample of 234 teeth with carious lesions per group is estimated. Consequently, 78 children are necessary per group.

Recruitment

To achieve adequate enrolment, parents/caregivers of the participating preschool children will be informed about the characteristics of ECC, its complications and repercussions that compromise or negatively impact the child’s oral health, general health and quality of life, as well as the parents’ or caregivers’ own health and quality of life. A video providing information on SDF (technique, advantages and disadvantages) will be provided via mobile phone contact.

Additionally, oral health education will be provided to all participating parents/caregivers and children prior to both treatments. The education will be based on oral health educational units, including the importance of proper oral hygiene, brushing techniques, fluorides and controlling a diet rich in fermentable carbohydrates. The educational units will be carried out in two stages.

• Group education for parents/caregivers and preschool teachers.

• Group education for children using age-appropriate educational strategies and language.

Randomisation

The child will serve as the unit of randomisation, indicating that all eligible teeth of a child involved in our trial will receive uniform treatment, irrespective of the number of carious lesions present. Randomisation will be computer generated. The interventions will be randomised using permuted blocks of four. The concealment of the random sequence will be done through a centralised assignment. The clinician will be informed of the participant’s assigned treatment group via telephone just before the procedure begins. The treatment assignment will not be known to parents/caregivers or the clinical operator until it is applied. SDF will be considered the intervention group, and ART will be the control group.

Implementation

The project’s principal investigator (PI) will oversee the assignment sequence. The examiner will register participants, and the PI will assign them to interventions. The field coordinator will enrol children who were screened (through baseline screening) and who meet the eligibility criteria.

Blinding

Considering the treatment types, it will not be possible to mask operators, examiners or participants.

Data collection methods

A customised clinical record will be used to consider the variables. At the onset of the study, the child’s parent/caregiver will be asked to answer a questionnaire regarding factors associated with ECC, cointerventions and modifying effects, such as some sociodemographic, biological and behavioural aspects. The questionnaire includes items on gender, socioeconomic status, medical history, access to dental care, cariogenic diet, use and frequency of breastfeeding, prolonged breastfeeding, exposure to fluorides and hygienic habits, among others.

The evaluation of the acceptability of the treatment by the parents/caregivers will integrate a quantitative and qualitative method, which will be conducted in two phases.

• Phase 1: quantitative method—a parent survey with acceptability questions will be applied to all parents or caregivers. The questionnaire will have been previously evaluated and agreed on by a group of experts in cariology and clinical epidemiology. Parents/caregivers should also complete the ECOHIS, which is validated for use in the Chilean population.⁴⁰

• Phase 2: qualitative method—an individual semistructured interview will be applied to the parents/caregivers identified as having the highest/lowest treatment acceptability after application of the survey in phase 1, corresponding to a sample of approximately 20% of the parents/caregivers of the children receiving treatment (above 90% treatment acceptability and below 10% treatment acceptability). These interviews will be conducted at an agreed-on time via an online platform with each participant. An interview script (online supplemental file 2) will be used to initiate the interview, which may be supplemented with follow-up questions if the interviewer considers it necessary to explore emerging issues in greater detail. The interview will last approximately 20 min and will be recorded with the participant’s consent. The interviewer will have a printed interview guide where they can take notes regarding the context or make explanatory notes that may be useful for the analysis. Participants will be contacted again if, during the analysis process, it is necessary to clarify what was said (in case of difficulties with the recording) or contribute to understanding the meanings given. The interviews will be transcribed verbatim on completion.

Plans to promote participant retention and data management

To promote participant retention and complete follow-up, data collection will include the child’s identification number and the telephone contact of the responsible parent/caregiver. Children who migrate to other schools in the city can be located with their identification number through the registry available at the regional education department. The data will be recorded on an excel spreadsheet.

Data analysis

Effectiveness

A descriptive sample analysis will be performed by comparing the demographic and clinical characteristics of the study groups. Tables will be created to show the distributions of variables at the time of recruitment and during the follow-up periods. The primary inferential analysis will be performed on an intention-to-treat basis, that is, all participants will be analysed in the group to which they were randomised, regardless of subsequent events (withdrawal from the study, protocol deviation, etc.); therefore, the last data recorded for each outcome variable will be included in the analysis. Association between groups and outcome variables will be evaluated using the χ2 test for categorical variables and the t-test or Mann–Whitney for continuous variables. Since multiple teeth with carious lesions will be analysed per child, a multilevel logistic regression model adjusted for significant covariates will be used to account for within-child clustering.

Acceptability

The quantitative analysis (phase 1) of the data obtained from the survey of parents/caregivers will describe the distribution of the parents/caregivers’ degree of acceptability.

In phase 2, the research team will review the transcripts of the interviews to ensure that they have been transcribed accurately and comprehensibly. The interviewer’s notes will also be reviewed to understand the contextual information. The interviews will be analysed following the phases and stages suggested by Vaismoradi et al⁴² with the help of ATLAS.ti 25 software.

Change in OHRQoL

The data analysis obtained from the ECOHIS survey will describe the distribution of changes in the OHRQoL perceived by parents/caregivers. The magnitude of change between the baseline and evaluation periods will be quantified through effect size, which is calculated as the difference between means divided by the pooled SD of the two groups.⁴⁰ Effect sizes of 0.2, 0.5 and 0.8 represent small, moderate and large clinical changes, respectively.

Adverse effects

A per-protocol analysis will be performed to avoid underestimating magnitude. Only patients who received the intervention to which they were assigned by randomisation and completed follow-up will be included in the analysis.

An interim analysis was not considered since the follow-up time is short term.

The significance level for all tests will be set at p<0.05. Data analysis will be performed using Stata 18 software (StataCorp, College Station, TX, USA).

Missing data

Some degree of missing data is expected due to participant withdrawal, loss to follow-up or incomplete follow-up assessments. To minimise missing data, participants and caregivers will be proactively contacted via phone calls and text messages to provide reminders. Additionally, study staff will receive training to ensure the collection of complete and accurate data at each assessment period.

A multiple imputation by chained equations procedure will be conducted under the assumption that data are missing at random. The imputation model will include baseline characteristics (eg, age, sex and baseline caries activity), treatment group and all outcome variables associated with either missingness or the outcome. Then, we apply the main analysis model specified for each outcome to each of the imputed datasets. Finally, we will conduct the following sensitivity analyses to evaluate the impact of missing data and deviations from the assigned intervention.

• Complete-case analysis, including only participants with observed data.

• Per-protocol analysis, including only participants who received the assigned intervention and completed follow-up.

• Best–worst and worst–best case analyses (only for binary outcomes), in which missing values are replaced with the most and least favourable plausible outcomes for each treatment arm.

Trial status

Protocol V.1.0 (21 January 2025). The first participant will be enrolled on 15 December 2025. Data collection for the primary outcome measures is scheduled to be completed on 28 February 2026. Data collection for the primary outcome measures, secondary outcome measures and adverse event information is scheduled to be completed on 28 February 2027. This trial is registered at www.clinical-trials.gov (NCT06786975), published on 21 January 2025.

Ethics and dissemination

This protocol was approved by the Scientific Ethics Committee (CEC) of the Universidad de La Frontera (Resolution No. 049_19) and adheres to the principles of the Declaration of Helsinki and Good Clinical Practice.

Protocol amendments

The study’s execution will be assessed at the end of the first 6 months. If any modifications are necessary, a letter will be sent to the CEC for approval. If approved, the Clinical Trials will be informed.

Informed consent

The PI or field coordinator will lead the informed consent process at participating preschools. Parents/caregivers will receive study information through a video and an informative document presented by the PI or coinvestigators. Consent forms will be distributed (onlinesupplemental files 3 4), and questions can be addressed in person, by phone or via email. Participants are required to sign the consent form before the start of their clinical examination appointment. Those selected for the qualitative phase will be contacted by phone and asked to sign an additional consent form during the interview.

All data will be kept confidential and anonymised using numerical identifiers. Only project staff will have access to participants’ identities. Digital data will be encrypted and stored on a secure computer at the university’s faculty of dentistry, while physical records will be kept in a locked cabinet for 15 years, in accordance with Chilean regulations (Decree 41, Law 20,584). The research team will use the data to prepare scientific reports and publications.

The situations arising from the treatments do not represent potential harm and/or damage to the participant. A follow-up will allow for the timely management of any negative effects affecting the participants. Any emergencies arising from the intervention will be referred to local healthcare facilities or the university’s Dental Teaching Clinic for resolution.

Data sharing plan

Study protocol, statistical analysis plan and the informed consent form will be available in the published protocol. The final, anonymised individual participant data (including the statistical code) that underlie the results will be available on reasonable request. Data sharing will commence after publication of the primary results and will remain accessible for a minimum of 5 years. Proposals must be methodologically sound and sent to patricia.munoz@ufrontera.cl. Data users must formally sign a data access agreement to ensure compliance with ethical guidelines and participant privacy. Shared data will strictly exclude any direct or indirect identifiers. All researchers using the data must agree to acknowledge the original researchers and the trial’s funding source.

Dissemination

The findings of this study will be presented at relevant conferences and published in peer-reviewed journals on completion of the trial and data analysis.