Effectiveness of Using Silver Diammine Fluoride Solution and Combination of Povidone Iodine and Sodium Fluoride Varnish in Preventing Dental Root Caries in Elders: a Randomized, Double-blind, Non-inferiority Trial
Phase: NA
Conditions: Root Caries
Sponsor: The University of Hong Kong

 
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Study title:  
Effectiveness of using silver diammine fluoride solution and 
combination of povidone iodine and sodium fluoride varnish in 
preventing dental root caries in elders: a randomized, double-
blind, non-inferiority trial 
 
Protocol version: 1 
 
Date: 3 March, 2016  
 
Approved by: the IRB of the University of Hong Kong and Hong Kong 
Hospital Authority Hong Kong West Cluster on March 17, 2016 
   Reference number: UW 16-162 
 

 
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Project title :  Effectiveness of using silver diammine fluoride solution and 
combination of povidone iodine and sodium fluoride varnish 
in preventing dental root caries in elders: a randomized, 
double-blind, non-inferiority trial 
 
Principal Investigator :   Prof. Edward C.M. LO  
 
 
(Faculty of Dentistry, University of Hong Kong) 
 
    
Co-investigators :  
Dr. Katherine C.M. LEUNG 
 
 
 
 
Dr. Chun Hung CHU 
 
 
(Faculty of Dentistry, University of Hong Kong) 
 
 
 
Summary 
 
Dental caries (tooth decay) is common among elders in Hong Kong and worldwide, 
placing heavy burden on the dental care services. There is an urgent need to develop effective 
and practical management approaches to improve the dental caries situation in the elders, 
especially among those living in residential care homes whose dental caries status is amongst 
the worst. The main objective of this study is to compare the effectiveness and cost-
effectiveness of 4-monthly application of 10% povidone iodine solution followed by 5% 
sodium fluoride varnish with those of annual application of 38% silver diammine fluoride 
solution on the prevention of new dental root caries in elders. A secondary objective is to 
compare the effectiveness of the two interventions mentioned above on arresting (halting the 
progression) active root surface caries in the elders, thus avoiding the need for placing dental 
restorations. 
 
This proposed study is a randomized double-blind controlled clinical trial with 24-month 
follow-up. A total of 332 elders aged 60 years or above living in residential homes or 
attending long-term care facilities in different districts in Hong Kong will be recruited. This 
sample size is sufficient for appropriate statistical analysis of non-inferiority with power set at 
90% and allowing for a 20% dropout. Baseline clinical examination will be conducted by a 
single calibrated examiner in the homes using an intra-oral LED light, dental mirrors and 
probes. Subjects will be randomly allocated to one of the two study groups: 1) positive 
control - receive annual application of 38% silver diammine fluoride solution; and 2) test - 
receive application of 10% povidone iodine solution followed by application of 5% sodium 
fluoride varnish every 4 months. Follow-up examinations will be carried out after 12 and 24 
months by the same blinded examiner to assess the clinical outcomes, i.e. whether new dental 
caries has developed and whether the active root surface caries lesions found at baseline have 
become arrested (hardened). Results of this study will provide the much needed evidence to 
guide the dental professionals in Hong Kong and worldwide in deciding on the most 
appropriate intervention for the prevention and management of dental caries in the older 
adults, especially those living in institutions. 
 
 

 
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1. 
Background 
 
With ageing of the population in most of the economically well-developed areas, tooth 
decay in the elders has become an important dental public health issue and a heavy burden on 
the oral health care system. The latest Hong Kong territory-wide oral health survey conducted 
by the government in 2011 found that 48% of the 65-74 year-old community-dwelling elders 
had untreated dental caries and 25% of them had root surface caries (Department of Health, 
2013). Furthermore, the same survey found that the dental caries situation of the elders who 
lived in residential care homes or attended long-term care facilities was worse. The 
institutionalized elders are a high risk group for dental caries in Hong Kong as well as in 
other countries (Chalmers et al., 2002).   
  
Untreated tooth decay can lead to pain and loss of teeth, and affect general health. Thus, 
there is an urgent need to develop effective preventive and management measures to improve 
the dental caries situation among the elders, especially those living in residential care homes. 
The Hong Kong government financially support non-profit-making non-governmental 
organizations (NGO) to establish dental outreach teams to provide on-site basic dental care 
services to the elders who are receiving long-term care. At present, there are around 20 NGO 
dental outreach teams serving over 30,000 elders in most of the residential care homes 
throughout Hong Kong. The dental outreach teams, consisting of dentists and dental 
assistants, bring along hand instruments and portable dental equipment to the residential 
homes and provide on-site dental examination, oral health education, prevention, scaling and 
simple dental restorations (Lo et al., 2004). The services of the outreach dental teams follow a 
general protocol, and are coordinated and monitored by the government Department of 
Health. 
 
 
In a recent systematic review by Gluzman and co-workers (2013), eight preventive 
agents for preventing dental root caries in older adults were identified. In the conclusion, they 
recommended that the best choice for primary prevention of root caries was annual 
application of 38% SDF solution while that for secondary prevention of root caries, i.e. 
arresting active lesions, was professional application of 5% NaF varnish every 3 months.  
 
In a randomized clinical trial with 3-year follow-up conducted among 306 elders 
living in 21 residential homes in Hong Kong (Tan et al., 2010), it was found that compared to 
the controls who only received regular oral hygiene instructions, annual topical application of 
38% SDF solution could reduce development of new root caries by 71%. The same study also 
found that application of 5% NaF varnish every 3 months could prevent root caries as well 
but the prevented fractions were lower than that of SDF solution. It was also found that 
presence of visible plaque on root surface was a significant risk factor for dental caries, 
highlighting the need for good plaque control (Tan & Lo, 2014). 
 
Povidone iodine is a newer antiseptic agent for dental use with clinical evidence 
showing that it is able to inhibit the activities of acidogenic bacteria including (Evans et al., 
2015). In a controlled clinical trial on 30 children with severe early childhood caries, it was 
found that application of 10% povidone iodine every 3 months significantly reduced the 
amount of Streptococcus mutans and caries development over the 12-month study period 
(Simratvir et al., 2010). Whether the caries prevention effect of fluoride varnish can be 
enhanced by regular use of an effective anti-plaque agent such as povidone iodine needs to be 
assessed by conducting randomized clinical trials.  
 

 
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2. 
Objectives of the study 
 
1. 
The primary objective is to compare the effectiveness and cost-effectiveness of 4-
monthly application of 10% povidone iodine solution followed by 5% NaF varnish with 
those of annual application of 38% SDF solution, used as a positive control, in 
preventing new dental root caries in elders who live in residential homes or attend long-
term care facilities.. 
 
2. 
The secondary objective is to compare the effectiveness and cost-effectiveness of the 
above two methods in arresting active root surface caries among these elders. 
 
 
 
Null hypotheses to be tested: 
 
1. In this non-inferiority randomised controlled trial, the primary hypothesis to be tested is 
that 4-monthly application of 10% povidone iodine solution and 5% sodium fluoride 
varnish is at least not appreciably worse than a 38% SDF solution in preventing new 
dental root caries development over a 24-month period. The primary outcome measure is 
the development of new root surface caries lesions in the teeth of the elders. 
 
2. The secondary hypothesis to be tested is that 4-monthly application of 10% povidone 
iodine solution and 5% sodium fluoride varnish is at least not appreciably worse than a 
38% SDF solution in arresting active root caries over a 24-month period. The secondary 
outcome measure is the conversion of active (soft/demineralized) root surface caries 
lesions to inactive (hard/remineralized) lesions. 

 
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3.  Methods and Materials 
 
3.1. Study population 
 
The study population of this proposed clinical trial is adults aged 60 years and above 
living in residential care homes or attending long-term care facilities in Hong Kong. The 
subject inclusion criteria are: 
1. have at least 6 teeth which are not indicated for extraction, and 
2. have basic self-care ability. 
 
Adults with one or more of the following conditions will be excluded: 
1. have serious debilitating health/medical conditions, and 
2. have cognitive problems or major problems in communication. 
 
About 10 residential care homes or long-term care institutions served by NGO dental 
outreach teams in various districts with different background, such as private or publicly 
funded homes, will be selected by the PI in consultation with the NGOs. All elders living in 
the selected residential homes will be invited to attend a free dental examination. Elders 
fulfilling the inclusion criteria will be invited to participate in this study and informed written 
consent will be obtained before commencement of the study. Dental treatments other than the 
study interventions will be provided by dentists from the NGOs which serve the residential 
homes. 
 
 
3.2. Sample size 
 
This non-inferiority trial aims to compare the caries preventive effect of applications 
of 38% SDF solution and that of combined 10% povidone iodine solution and 5% NaF 
varnish. A non-inferiority margin of 0.8 surface for the difference in the mean number of new 
caries surfaces over the 24-month study period is considered not clinically significant. The 
estimated sample size is based on the lower limit of the 2-sided 95% confidence interval for 
the difference set above the non-inferiority margin and the statistical power of the study being 
set at 90% (β=0.10). The estimated standard deviation is 2.0, based on the results of a 
previous clinical trial conducted in Hong Kong (Tan et al., 2010). Using the statistical power 
analyses software, G*Power (version 3.1.7; Franz Faul, Universität Kiel, Kiel, Germany), the 
total required number of elders in each group is calculated to be 133. Allowing for a drop-out 
rate of 20% in this 24-month study, an initial sample size of 166 subjects in each group or a 
total of 332 subjects is needed. 
 
With a total sample size of 332 subjects and an estimated mean number of one 
untreated early/shallow root caries lesions per subject (Department of Health, 2013), there 
will be 332 root caries lesions in total or 166 lesions in each study group for caries arrest 
treatment. With this sample size, there is approximately 85% power that an absolute 15% 
difference in dental caries arrest rates between two groups can be shown to be statistically 
significant at the 5% level using Chi-square test when the overall success rate of the caries 
arrest treatment is around 80%. 
 
 

 
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3.3. The baseline and follow-up examinations 
 
 
The baseline and follow-up examinations after 12 and 24 months will be carried out in 
the residential home by a single trained examiner. A portable dental chair, an intra-oral LED 
light, disposable dental mirrors and CPI probes will be used in the examination.  
 
 
For each tooth that is not indicated for extraction, status of its crown and its root will be 
assessed and recorded separately. Caries diagnosis is based on visual and tactile inspection. 
No radiograph will be taken. Plaque and food debris that obscures visual inspection of the 
tooth surfaces will be removed. Four surfaces (mesial distal, buccal and lingual) per tooth 
will be examined and the status will be recorded using the following codes which basically 
follow the criteria recommended by the International Caries Detection and Assessment 
System (ICDAS II) Coordinating Committee (2009). 
 
 
The oral hygiene status of the subject will be assessed and recorded by using the Visible 
Plaque Index (Ainamo & Bay, 1975). The presence or absence of visible plaque will be 
recorded on four surfaces (mesial, distal, buccal and lingual) per tooth. 
 
 
The gingival status of the subject will be assessed and recorded using by the Gingival 
Bleeding Index (Ainamo & Bay, 1975). The presence or absence of bleeding within 10 
seconds after running a probe across the gingival margin will be recorded on four surfaces 
(mesial, distal, buccal and lingual) per tooth. 
 
 
Other information that will be recorded included whether the subject normally wears a 
removable partial denture or not, and the subject’s general health status and medications that 
affect saliva flow rate.  
 
 
The same examiner will carry out all the baseline and follow-up examinations without 
knowing the study group assignment of the subjects. It has been shown that good intra-
examiner reproducibility can be achieved after training (Tan et al., 2010) and a random 
sample of 10% of the subjects will be re-examined during each examination to monitor intra-
examiner reproducibility. 
 
 
At the examinations, the subjects will be asked to report on their oral hygiene practices, 
use of fluoridated toothpaste and other topical fluoride agents, and use of dental services 
during the study period. 
 
 
3.4. Interventions 
 
Oral health education talk and instructions on how to keep good oral hygiene will be 
provided at baseline and every year to all the elders in the selected residential homes. 
Standard fluoride toothpaste with 1000-1500 ppm fluoride will be provided free to all the 
elders in the selected residential homes over the 24-month study period. 
 
After the baseline examination, subjects satisfying the inclusion criteria of the study 
will be stratified into two groups according to the number of natural teeth in their mouth, 
those with 12 or fewer teeth and those with 13 or more teeth. The subjects will then be 
assigned to one of the two study groups by a research assistant using a block randomization 
method with a block size of 6. The stratified randomization procedure will help to ensure that 

 
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the numbers of teeth involved in the two study groups are balanced. The group assignment of 
the study subjects will be concealed and placed in a sealed envelope, and will not be made 
known to the examiner who evaluate the study outcomes.  
 
The interventions for the two study groups will be provided by other dentists and are 
described below:  
 
Group 1 – plaque on the root surfaces of all teeth in the subject’s mouth will be removed by a 
small brush and a 38% SDF solution (Saforide, Toyo Chemical, Japan ) will be 
applied onto the root surfaces using a microbrush/applicator. This will be repeated 
every year. 
 
Group 2 – plaque on the root surfaces of all teeth in the subject’s mouth will be removed by a 
small brush and a 10% povidone iodine solution (Betadine, Mundipharma, 
Switzerland) will be applied, then followed by application of a 5% sodium 
fluoride varnish (Duraflor, Medicom, Canada) using a microbrush/applicator. This 
will be repeated every 4 months. 
 
 
3.5. Statistical analysis 
 
The collected data will be entered into a computer and analyzed using the software 
SPSS for Windows version 20. T-test and Chi-square test will be used, as appropriate, to 
assess the differences in the distribution of age, gender, denture wearing, number of 
remaining teeth, number of active caries lesions, oral hygiene practice and status, and 
gingival status at baseline between the two study groups.  
 
The number of root surfaces with new caries found at each follow-up examination 
will be calculated. Two-sample t-test test will be used to find out if there are statistically 
significant differences between the two study groups in the number of tooth surfaces that 
have developed new dental caries. Both intention-to-treat and per protocol analysis will be 
performed to compare the effectiveness and efficacy of the two study preventive methods.  
 
Two-level, tooth surface and subject, survival analysis will be used to assess the rates 
of arrest of active root surface caries in the two study groups (Wong et al. 2005).  The 
statistical significance level for all tests will be set at 5%. 
 
 
 

 
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4. 
References 
 
1. 
Ainamo J, Bay I (1975). Problems and proposals for recording gingivitis and plaque. 
Internationl Dental Journal 25:229-35. 
 
2. 
Chalmers JM, Hodge C, Fuss JM, Spencer AJ, Carter KD (2002). The prevalence and 
experience of oral diseases in Adelaide nursing home residents. Australian Dental 
Journal 47:123-130. 
 
3.  
Department of Health (2013). Oral Health Survey 2011. Hong Kong: Government 
Printer. 
 
4. 
Evans A, Leishman SJ, Walsh LJ, Seow WK (2015). Inhibitory effects of antiseptic 
mouthrinses on Streptococcus mutans, Streptococcus sanguinis and Lactobacillus 
acidophilus. Austrian Dental Journal 60:247-54. 
 
5. 
Gluzman  R, Katz RV, Frey BJ, McGowan Richard (2013). Prevention of root caries: a 
literature review of primary and secondary preventive agents. Special Care Dentistry 
33:133-140. 
 
6. 
ICDAS 
Coordinating 
Committee 
(2009). 
Criteria 
manual. 
URL: 
www.icdasfoundation.dk/ 
 
7. 
Lo ECM, Luo Y, Dyson JE (2004). Outreach dental service for persons with special 
needs in Hong Kong. Special Care Dentistry 24:80-85. 
 
8. 
Simratvir M, Singh N, Chopra S, Thomas AM (2010). Efficacy of 10% povidone iodine 
in children affected with early childhood caries: an in vivo study. Journal of Clinical 
Pediatric Dentistry 34:233-238. 
 
9. 
Tan HP, Lo ECM, Dyson JE, Luo Y, Corbet EF (2010).  A randomized trial on root 
caries prevention in elders.  Journal of Dental Research 89:1086-1090. 
 
10. Tan HP, Lo ECM (2014). Risk factors for root surface caries in institutionalized elders. 
Community Dentistry and Oral Epidemiology 42:435-440. 
 
11. 
Wong MCM, Lam KF, Lo ECM (2005). Bayesian analysis of clustered interval-
censored data.  Journal of Dental Research 84:817-821.