Abstract • Objective: Two randomized, six-week, double-blind, parallel group, clinical trials were independently conducted to compare the extrinsic stain removal efficacy of a novel whitening therapeutic dentifrice containing 0.454% stannous fluoride and sodium hexa- metaphosphate in a formulation with high cleaning silica, relative to a positive control whitening dentifrice. • Methodology: Generally healthy adults, 56 for study 1 and 60 for study 2, with visible extrinsic tooth stain were enrolled in the studies. At the baseline visit, stain was assessed on the facial surfaces of the eight central and lateral incisors using the modified Lobene Stain Index. Oral soft and hard tissue examinations were also conducted. In each study, subjects were randomized to either the stannous fluoride + sodium hexametaphosphate toothpaste (Crest ® Pro-Health ® ) or the positive control toothpaste (Colgate ® Total ® Plus Whitening) to use twice per day for six weeks. Stain and safety were reassessed at weeks three and six. • Results: Fifty-two and 58 subjects completed studies 1 and 2, respectively. In each study, there were no statistically significant differences in Lobene composite stain scores between the two treatment groups across all three visits. Both groups showed statistically significant reductions in Lobene composite stain scores at week three (p < 0.0001) and week six (p < 0.0001) relative to baseline. The percent of Lobene composite scores with a greater than 0.5 unit reduction from baseline at week six was 86% for study 1 and 97% for study 2 for the stannous fluoride + sodium hexametaphosphate dentifrice group. • Conclusion: Collectively, these two stain removal clinical trials demonstrate the statistically significant extrinsic stain removal efficacy for the stannous fluoride + sodium hexametaphosphate dentifrice relative to baseline. There were no statistically significant differences between the stannous fluoride + sodium hexametaphosphate dentifrice and positive control treatment group. (J Clin Dent 18:7–11, 2007) Extrinsic Stain Removal Efficacy of a Stannous Fluoride Dentifrice with Sodium Hexametaphosphate Tao He, DDS, PhD Robert Baker, MS Robert D. Bartizek, MS Aaron R. Biesbrock, DMD, PhD Procter & Gamble Health Care Research Center Mason, OH, USA Eros Chaves, DMD Geza Terézhalmy, DDS, MA Hill Top Research Inc. University of Texas Health Science Center West Palm Beach, FL, USA San Antonio, TX, USA 7 Introduction As patient demand for tooth whitening treatments has in- creased, so has the need for oral care products to sustain the whitening effect. The use of dentifrices formulated with agents to control extrinsic stain is one common approach. Various ingre- dients have been used in dentifrices for this purpose, including peroxide, abrasives, and chemical agents. 1 Peroxide is a well- established bleaching agent in delivery systems with barriers to promote contact time, but its effectiveness in dentifrices and other barrier-free forms is limited due to brief contact time with the tooth surface and formulation challenges. 2,3 Abrasives are insoluble ingredients (e.g., silica), commonly used to remove surface stain by physical action. 1 Chemical agents (e.g., pyro- phosphates) help maintain whitening due to their strong affinity for tooth minerals. As they are adsorbed to mineral sites, they help desorb pellicle proteins containing stain. 4 In 2001, sodium hexametaphosphate was introduced in a denti- frice. 4 This chemical whitening agent is in the same class of “cal- cium phosphate surface active builders” as pyrophosphate, a tradi- tional ingredient used to inhibit surface stain and calculus. Sodium hexametaphosphate is a longer-chain variant, with 10–12 repeating pyrophosphate subunits, so it has a greater affinity for, and reten- tion on the tooth surface compared to pyrophosphate. 4 The polymer chains interact with the stain-trapped pellicle films to lift stain ma- terial in the pellicle and prevent the adsorption of new chromogens. Numerous clinical and technical studies demonstrate the stain removal and prevention properties of sodium hexametaphos- phate in dentifrice and chewing gum forms. 5-11 Gerlach and col- leagues reported a 29% reduction in composite stain relative to a negative control after six-weeks’ use of a dentifrice containing 7% sodium hexametaphosphate. 5 Other randomized controlled clinical trials have shown significant stain removal and preven- tion when subjects used a dentifrice containing sodium hexa- metaphosphate. 6,7 Reports in the literature also provide evidence of the agent’s ability to lift and repel surface stains when deliv- ered in chewing gums. 8-11 Most recently, sodium hexametaphosphate has been integrated into a high cleaning silica-based dentifrice with 0.454% stabi- lized stannous fluoride. 12 This antibacterial fluoride provides a unique range of therapeutic benefits relative to other fluoride salts, including protecting against caries, plaque, gingivitis, and dentinal sensitivity. Its use has historically been limited, however, due in part to its potential for extrinsic stain formation. 13 The objective of these two six-week studies was to assess the stain removal benefit delivered in this novel sodium hexa- metaphosphate + stannous fluoride dentifrice in subjects with pre-existing natural extrinsic stain. The studies included a positive control whitening dentifrice, which has been shown to significantly reduce extrinsic stain in multiple clinical trials. 14-16