Incentive programmes for smoking cessation: cluster randomized trial in workplaces in Thailand.

OBJECTIVE: To compare several monetary incentive programmes for promoting smoking abstinence among employees who smoke at workplaces in a middle income country. DESIGN: Parallel group, open label, assessor blinded, cluster randomized controlled trial. SETTING: Large industrial workplaces in metropolitan Bangkok, Thailand. PARTICIPANTS: Employees who smoked cigarettes and planned to quit within six months recruited from 101 worksite clusters (84 different companies). INTERVENTIONS: Worksites were digitally cluster randomized by an independent investigator to usual care or usual care plus one of eight types of incentive programmes. Usual care consisted of one time group counseling and cessation support through a 28 day text messaging programme. The incentive programmes depended on abstinence at three months and varied on three intervention components: refundable deposits, assignment to a teammate, and bonus size ($20 (£15; €17) or $40). MAIN OUTCOME MEASURES: The primary outcome was biochemically verified seven day point prevalence smoking abstinence at 12 months. Secondary outcomes were programme acceptance at enrollment and smoking abstinence at three months (end of intervention) and at six months. All randomized participants who had complete baseline information were included in intention-to-treat analyses; participants with missing outcomes were coded as continuing smokers. RESULTS: Between April 2015 and August 2016, the trial enrolled 4190 participants. Eighteen were omitted because of missing baseline covariates and death before the primary endpoint, therefore 4172 participants were included in the intention-to-treat analyses. Programme acceptance was relatively high across all groups: 58.7% (2451/4172) overall and 61.3% (271/442) in the usual care group. Abstinence rates at 12 months did not differ among deposit programmes (336/2253, 14.9%) and non-deposit programmes (280/1919, 14.6%; adjusted difference 0.8 points, 95% confidence interval -2.7 to 4.3, P=0.65), but were somewhat lower for team based programmes (176/1348, 13.1%) than individual based programmes (440/2824, 15.6%; -3.2 points, -6.6 to -0.2, P=0.07), and higher for $40 bonus programmes (322/1954, 16.5%) than programmes with no bonus (148/1198, 12.4%; 5.9 points, 2.1 to 9.7, P=0.002). The $40 individual bonus was the most efficacious randomization group at all endpoints. Intervention components did not strongly interact with each other. CONCLUSIONS: Acceptance of monetary incentive programmes for promoting smoking abstinence was high across all groups. The $40 individual bonus programmes increased long term smoking abstinence compared with usual care, although several other incentive designs did not, such as team based programmes and deposit programmes. Incentive design in workplace wellness programmes might influence their effectiveness at reducing smoking rates in low resource settings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02421224).

A randomized, placebo-controlled trial to assess the safety and acceptability of use of carraguard vaginal gel by heterosexual couples in Thailand.

OBJECTIVES: To determine the safety and acceptability of use of Carraguard, a carrageenan-derived candidate microbicide gel, during sexual intercourse in women and men. STUDY DESIGN: We conducted a 6-month randomized, placebo-controlled trial among sexually active, couples at relatively lower risk for HIV infection in northern Thailand. METHODS: Women inserted 1 applicator of study gel vaginally every time the couple had sex. Safety was assessed by symptom report and genital examination of both partners and by changes in vaginal flora. Acceptability was assessed by participant interview. RESULTS: Overall, 55 couples were randomized, 28 to Carraguard use and 27 to the methyl-cellulose placebo gel group. Retention and study gel use were similarly high in both study groups; use of gel without condoms was reported in more than 95% of vaginal sex acts. The 2 study groups were similar in the proportions of women and men with symptoms or with genital findings without epithelial disruption, of men with findings with epithelial disruption, and of women with abnormal genital flora, whereas more women in the placebo group had findings with epithelial disruption. Women and men in both groups reported that the gel and applicator were acceptable. CONCLUSIONS: Carraguard can safely be used an average of 2 to 3 times per week during sex and is acceptable to Thai women and men.

No increase in cervicovaginal proinflammatory cytokines after Carraguard use in a placebo-controlled randomized clinical trial.

BACKGROUND: Assessment of cervicovaginal cytokine levels may be helpful to evaluate subclinical epithelial inflammation during safety evaluations of candidate microbicides. METHODS: Fifty-five HIV-seronegative Thai women were enrolled in a safety trial of the candidate microbicide Carraguard and were randomized to use Carraguard or placebo gel before vaginal sex. Cervicovaginal lavages were collected at baseline and after 1 month of gel use; levels of interleukin (IL)-1beta, IL-6, IL-8, and secretory leukocyte protease inhibitor (SLPI) were measured using microwell plate-based enzyme immunoassays. Median levels were compared between the baseline and 1-month follow-up visits using paired t tests; the median change between groups was compared using Wilcoxon rank sum tests. Women were examined for the presence of genital findings; the association between genital findings and cytokine levels was studied. RESULTS: No increase in levels of proinflammatory cytokines after use of Carraguard gel or placebo gel was observed during the study. The median change from the baseline to 1 month of follow-up was not significantly different between Carraguard and placebo groups (IL-1beta: -0.3 pg/mL vs. -3.93 pg/mL; P = 0.4, IL-6: -0.3 pg/mL vs. 0 pg/mL; P = 0.3, IL-8: -40.1 pg/mL vs. -53.2 pg/mL; P = 0.8, and SLPI: -26.5 pg/mL vs. 12.6 pg/mL; P = 0.07). Genital findings with intact epithelium were found in 16 (29%) women; these women tended to have somewhat higher IL-6 levels than those with normal epithelium (14.9 pg/mL vs. 8.8 pg/mL; P = 0.08). CONCLUSION: We found no increase in proinflammatory cytokines after Carraguard and placebo gel use, suggesting that neither gel causes inflammation. Further studies to assess the role of cytokines in microbicide safety studies are warranted.

Safety and acceptability of the candidate microbicide Carraguard in Thai Women: findings from a Phase II Clinical Trial.

OBJECTIVE: To determine the safety and acceptability of vaginal application of Carraguard, a carrageenan-derived candidate microbicide gel. DESIGN: A randomized, placebo-controlled, triple-blinded clinical trial was conducted in Chiang Rai, northern Thailand. METHODS: Women were asked to insert one applicator of study gel vaginally at least three times per week (with or without sex) and to use gel with condoms every time they had sex. Safety was assessed by visual inspection of the vagina and cervix, changes in vaginal flora and self-reported symptoms at day 14, month 1 and then monthly for up to 1 year. Acceptability was assessed through reported use of the gel, return of used and unused applicators, and quarterly interviews. RESULTS: One hundred sixty-five women were randomized: 83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use was similarly high in both groups throughout the trial with an average of four applicators per week. Carraguard use was not associated with abnormal genital clinical findings, abnormal vaginal flora, Pap smear abnormalities or other abnormal clinical signs or symptoms. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. Participants in both groups reported high acceptability. CONCLUSIONS: Carraguard can safely be used an average of four times per week with or without sex and is acceptable to Thai women. A Phase III efficacy trial of Carraguard is warranted and is currently ongoing in South Africa.