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. 2017 Mar 31;2017(3):CD008676. doi: 10.1002/14651858.CD008676.pub2

Anauate‐Netto 2014.

Study characteristics
Methods Trial design: parallel (3 arms ‐ 2 arms relevant to this review)
Location: dental clinics at University Bandeirante of Sao Paulo, Sao Paulo, Brazil
Number of centres: 1
Study duration: the recruitment period is not stated. Study duration and duration of rinsing was 4 weeks
Participants Participants: healthy adults
Inclusion criteria: at least 20 teeth, no clinical signs of periodontal disease, aged between 18 and 55 years, normal saliva secretion rate
Exclusion criteria: smokers, pregnancy, taking oral topical or systemic medication
Baseline gingivitis: (Papillary Bleeding Score) overall (3 groups) mean 1. Gp A: mean 1.1 (SD 0.5); Gp B: mean 1.0 (SD 0.5); Gp C: mean 0.9 (SD 0.4)
Age at baseline (years): overall: 40. Gp A: mean 41.6 (SD 13.4); Gp B: mean 39.4 (SD 9.8); Gp C: mean 39 (SD 11.7)
Gender: overall: male 24 (40%), female 36 (60%). Gp A: male 7 (35%), female 13 (65%); Gp B: male 8 (40%), female 12 (60%); Gp C: male 9 (45%), female 11 (55%)
Number randomised: 60 (Gp A: 20; Gp B: 20; Gp C: 20)
Number evaluated: 60 (Gp A: 20; Gp B: 20; Gp C: 20)
Interventions Comparison: CHX rinse versus propolis rinse* versus placebo rinse
Gp A (n = 20): CHX 0.12%, 15 mL, twice daily, duration not specified, 4 weeks
*Gp B (n = 20): alcohol‐free, 2% typified propolis (plus mint flavour, polioxyethelers, sorbitol, blue colour and water), 15 mL, twice daily, duration not specified, 4 weeks. We excluded this arm from the risk of bias and analysis
Gp C (n = 20): placebo (same ingredients as Gp B without the propolis), 15 mL, twice daily, duration not specified, 4 weeks
Prophylaxis at baseline: not reported
OHI: none given. Subjects followed their usual oral hygiene procedures
Non‐supervised rinsing
Timing of mouthrinsing in relation to toothbrushing: quote: "Rinsing was performed in the morning and before bedtime after ordinary oral hygiene procedures"
Outcomes Gingivitis (gingivial inflammation: Papillary Bleeding Score, gingival bleeding: PBS ≥ 2); adverse reactions; assessed at 4 weeks
Funding Quote: "This study was supported by a grant from FAPESP (Fundacao de amparo a pesquisado estado de Sao Paulo) protocol no. 2007/53047‐3"
Notes Sample size calculation: quote: "It was not possible to conduct a sample size and power analysis... because of lack of randomized clinical trials of propolis on gingivitis"
Adverse effects: Gp A (CHX): 23 reports (burning sensation, taste alteration, yellow teeth, breath alteration, tongue burning, mucosal irritation, bitter taste); Gp B (propolis): 7 reports (breath alteration, burning sensation, taste alteration, yellow teeth, bitter taste); Gp C (placebo): 9 reports (taste alteration)
Non‐smokers
Declarations/conflicts of interest: none stated
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "a computer‐generated list of random numbers was used"
Comment: adequate method of random sequence generation
Allocation concealment (selection bias) Low risk Quote: "Rinses were prepared in dark‐bottles, which were consecutively numbered according to the randomization schedule... Study coordinator, examiners, and participants were unaware of group allocation. The group identity was generated and kept in Florianopolis, SC, Brazil while the study was conducted in Sao Paulo, SP, Brazil"
Comment: remote/central randomisation should have ensured that the random sequence was implemented as it was generated, without any manipulation
Blinding of participants and personnel (performance bias)
All outcomes High risk Quote: "double‐blind placebo‐controlled" and "rinses
were prepared in dark‐bottles." The placebo mouthrinse matched the propolis mouthrinse without the active ingredient
Comment: the level of adverse reactions in the CHX group (n = 23) was higher than in the propolis (n = 7) and placebo groups (n = 9) may have meant that participants could have worked out which group they were in and this could have affected their oral health behaviours and hence the outcome.The direction of this potential bias is not clear
Blinding of outcome assessment (detection bias)
All outcomes High risk Quote: "double‐blind". The incidence of adverse reactions in the CHX group (n = 23) was higher than in the propolis (n = 7) and placebo groups (n = 9)
Comment: the authors do not report precisely who was blinded, but even if this includes the outcome assessors the higher level of adverse effects including tooth staining in the CHX group could have allowed the outcome assessors to work out which individuals were in the CHX group and could have affected the outcome assessment. The direction of this potential bias is not clear
Incomplete outcome data (attrition bias)
All outcomes Low risk All randomised participants were included in the analyses
Selective reporting (reporting bias) High risk All outcomes stated in the methods section are reported in the results section. Adverse effects including 'yellow teeth' are reported aggregated as the total number of participants affected by group. Insufficient information on tooth staining is reported for us to use the data in a meta‐analysis
Other bias Low risk Quote: "PBS measurements were performed by an experienced examiner (AAA). Intra‐examiner reliability exercises revealed a Kappa test score of 0.85, indicating adequate reproducibility of PBS measurements"
Comment: the potential for differential diagnostic activity was minimised.
Groups were balanced at baseline (NS differences) for age, gender and race. The groups appear balanced for PBS at baseline