Van Leeuwen 2017.

Methods	Trial design: parallel (6 groups) Location: Department of Periodontology of the Academic Centre for Dentistry, Amsterdam, the Netherlands Number of centres: 1 Study Duration: recruitment November 2009 to November 2010. Participants followed‐up at 12 months
Participants	Participants: "Participants were students recruited from different universities and colleges in and around Amsterdam by e‐mail and flyers" Inclusion criteria: ≥ 18 years of age, have a minimum of 5 evaluable teeth per quadrant, and have moderate to advanced gingivitis (≥ 40% bleeding on marginal probing (BOMP)) (Lie 1998; Van der Weijden 1994) Exclusion criteria: open caries, pockets of 4 mm to 5 mm in combination with gingival recession or pockets of ≥ 6 mm, as assessed according to the Dutch Periodontal Screening Index (DPSI) scores 3+ and 4 (Mantilla Gómez 2001; Van der Velden 2009), orthodontic appliances or removable (partial) dentures, a history of allergic reactions to erythrosine and/or any of the mouthrinse components, pregnancy, systemic disease or any adverse medical history or long‐term medication that might interfere with the response variables. No restriction with respect to smoking status was applied Age at baseline (mean years): Control I: 21.1 (SD 2.66); Control II: 21.4 (SD 2.99); OHI: 21.2 (SD 2.91); PP: 21.6 (3.36); OA + CHX: 21.9 (SD 3.17); COMBI: 20.6 (SD 2.19) Gender: male/female: Control I: 13/27; Control II: 11/33; OHI: 10/33; PP: 7/35; OA + CHX: 6/34; COMBI 6/32 Number randomised: 267 (Control I: 44, Control II: 45, OHI: 44, PP: 45, OA + CHX: 44, COMBI: 45) Number evaluated: 247 (Control I: 40, Control II: 44, OHI: 43, PP: 42, OA + CHX: 40, COMBI: 38)
Interventions	"All participants performed a similar basic oral hygiene regimen of brushing twice daily for 2 minutes with a fluoride‐containing dentifrice for the full duration of the study. At day 0 participants were instructed to brush according to the details provided in a written oral hygiene instruction leaflet describing the Bass method technique (Bass 1954a; Bass 1954b)" Control I and Control II: the participants in control groups I and II were instructed to adhere to this basic oral hygiene regimen only. To minimize the potential Hawthorne effect (Adair 1984), the clinical parameters of Control I were assessed at day 0, baseline (3 weeks later) and 12 months later. The clinical parameters of all other groups were assessed at day 0, baseline, 4, 7, 10 and 12 months OHI Group: the oral hygiene instruction group (OHI) received the same interventions as those in the control groups. Additionally they received professional individual oral hygiene instruction (at day 0) PP Group: the professional prophylaxis group (PP) received a professional oral prophylaxis from an experienced dental hygienist at day 0. This group is not further included in this review OA + CHX Group: "During the treatment phase from day 0 until baseline, the oxygenating‐agent (OA) and chlorhexidine (CHX) group (OA + CHX) were instructed to rinse with a combination of the OA Bocasan (Oral‐B Laboratories, Boston, MA, USA) and CHX 0.20% (Corsodyl; GlaxoSmithKline, Zeist, the Netherlands) twice daily for 3 weeks in addition to the basic oral hygiene." This group is not included further in this review COMBI Group: "In addition to the basic oral hygiene regimen, participants in the COMBI group received all 3 supplementary preventive interventions: OHI, PP and OA + CHX." This group is not included further in this review Prophylaxis provided: only for those in the PP Group. "Subjects were not allowed to use any other dental products or interdental cleaning aids during the study and/or to undergo a dental prophylaxis during routine dental check‐ups" Member of dental team delivering intervention: hygienist Frequency of intervention: 3‐week treatment phase, intervention administered once Intensity of intervention (length of time): not reported Setting: Department of Periodontology of the Academic Centre for Dentistry, Amsterdam Disease level: not reported ‐ students in Amsterdam
Outcomes	Baseline, 4 months, 7 months, 10 months, 12 months: ‐ staining was assessed (NLHH) at 4 sites per tooth, according to the Grundemann Modification of the Stain Index (GMSI), on a scale of 0 to 3 (Gründemann 2000) ‐ gingival health was assessed at 6 sites (mesio‐buccal, mid‐buccal, disto‐buccal, mesio‐lingual, mid‐lingual and disto‐lingual) around the selected quadrants by scoring BOMP on a scale of 0 to 2 (Lie 1998; Van der Weijden 1994) ‐ dental plaque was also assessed at 6 sites after disclosing with Mira‐2‐Ton (Hager & Werken GmbH & Co KG, Duisburg, Germany), and scores were based on the modified Quigley and Hein (Quigley 1962) plaque index (QHPI) with a scale of 0 to 5 12 months only: "Upon completion of the clinical assessments, all participants were asked to complete a questionnaire designed to evaluate their attitudes towards the assigned intervention.The participants answered the questions by placing a vertical mark on a 10‐cm‐long uncalibrated line (the visual analogue scale, VAS); the left of this line represented the 'negative' extreme, whereas the right represented the 'positive' extreme. As such, a mean score of 5 would represent an 'average' score, being neither positive nor negative"
Notes	Funding: The Netherlands Organisation for Health Research and Development Sample size calculation: "The sample size of 40 participants per group was calculated a priori (PS: Power and Sample Size program) (Dupont 1990) based on a pooled standard deviation (r) of 0.23 (as taken from the gingivitis scores in a previous 6‐month mouthrinse study by Paraskevas et al (Paraskevas 2005) and a detectable difference (d) of 0.18 (between groups) with an a = 0.05 to obtain 80% power" Adverse effects: not reported Declarations/conflicts of interest: "ACTA Dental Research BV received financial support from The Netherlands Organization for Health Research and Development (ZonMW). The authors designed, performed and analysed the study project without any interference from other parties. Van der Weijden, Rosema and Slot have formerly received either external advisor fees, lecturer fees or research grants from companies that produce mouthwash products. Among these were Colgate, Dentaid, GABA, Johnson & Johnson Lactona, Oral‐B, Philips, Procter & Gamble, Sara Lee, Sunstar, and Unilever. All authors declare that they have no conflicts of interest"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization for group and quadrant selection was performed (by CB) using true random numbers generated by sampling and processing a source of entropy outside the computer. The source was atmospheric noise, which was sampled and fed into a computer without any buffering mechanisms in the operating system (www.random.org). The study co‐ordinator assigned the participants to their randomly chosen group"
Allocation concealment (selection bias)	Low risk	Quote: "Allocation was concealed by using sequentially numbered, opaque, sealed envelopes (SNOSE‐method) (Schulz 2002)"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "The participants were not informed about the group allocation" Comment: personnel delivering oral hygiene instruction intervention would be aware of which group participant was in. Blinding of participants was not possible; it is unclear the influence this would have on the risk of bias for this domain
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quotes: "The examiners were blinded to treatment randomization, and the records of earlier examinations were not available at the time of re‐examination" and "The examiners were blinded with respect to treatment allocation"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: all participants lost to follow‐up accounted for including reason (e.g. "used another dentifrice," "absent without notice," etc.)
Selective reporting (reporting bias)	Low risk	All outcomes in methods section were reported
Other bias	Low risk	No apparent other bias