Efficacy and Safety of Cytisine in Combination with a Community Pharmacists’ Counselling for Smoking Cessation in Thailand: A Randomized Double-Blinded Placebo-Controlled Trial

Abstract

Background: Cytisine is a prospective pharmacological alternative for community pharmacy smoking cessation services. However, it has not yet been licensed because of a lack of efficacy and safety information in Thailand. Objective: The aim of this study was to evaluate the efficacy of cytisine in combination with community pharmacists’ counselling on smoking cessation in a community pharmacy in ThailandDesign. Setting, participants, and interventions: A double-blinded randomized placebo-controlled trials was carried out. Participants aged >18 years old who smoked >10 tobaccos/day were randomly assigned to receive cytisine or placebo and five sessions of counselling by a community pharmacist. The primary outcome was a continuous abstinence rate (CAR) at week 48. The CAR was also measured at weeks 2, 4, 12, and 24. Adverse events were monitored. Results: A total of 132 participants were included, with 67 receiving cytisine and 65 receiving a placebo. Approximately 95% of participants were male. The CARs were determined to be 14.93% and 6.15% for cytisine and placebo, respectively, at week 48. The relative risk (RR) was 2.41 (95% confidence interval (CI); 0.80–7.35, p = 0.102). The RRs for CAR at weeks 2, 4, 12, and 24 were 2.43, 2.91, 2.50, and 1.78, respectively. Only the RRs for weeks 2, 4, and 12 were statistically significant. Common and non-serious gastrointestinal and neurological adverse events were observed. Conclusion: Cytisine, when combined with community pharmacists’ counselling, did not statistically improve the CAR at week 48, although it did improve the CAR at weeks 2, 4, and 12. Adverse events of cytisine were common and non-serious (registration number: TCTR20180312001).

Evaluation of the effectiveness of cytisine for the treatment of smoking cessation: A systematic review and meta‐analysis

“…Eight RCTs [10–13, 15, 17, 19, 20] compared cytisine to placebo at the standard dose covering 5922 patients, 2996 of whom took cytisine, delivering a RR of 2.25, 95% CI = 1.42–3.56 (Figure 4: Forest plot of comparison: 1, cytisine versus placebo; outcome, 1.1 smoking cessation rate at longest follow‐up, with a high level of heterogeneity ( I 2 = 88%). Following sensitivity analysis, we pooled the findings of only five RCTs [11–13, 19, 20] covering 2134 patients, 1099 of whom took cytisine, delivering an RR of 3.46, 95% CI = 2.45–4.89 (Figure 5: Forest plot of comparison: 1, cytisine versus placebo, sensitivity analysis of outcome, 1.1) with a level of heterogeneity not relevant ( I 2 = 18%). Also following the sensitivity analysis, by removing from the analysis the trials classified as having a high risk of bias [14, 15], the effect estimates were unchanged (RR = 2.86; 95% CI = 1.73–4.73) and decreased the I 2 value to 9%.…”

“…Similarly, the analysis remained robust in other summary statistics, delivering an OR of 2.62 (95% CI = 1.52-4.49; I 2 = 27%). These trials reported smoking cessation at the longest follow-up: at 24 weeks [11], 48 weeks [20],…”

“…In this particular outcome, we pooled the findings of six RCTs [10,11,13,15,17,19,20] covering 5624 participants, delivering a RR (95% CI = 1.41-5.17) with an I 2 value of 93%. Removing the trials rated at high risk of bias [19,20] from the analysis, the effect estimates are unchanged (RR = 1.87, 95% CI = 1.11-3.14; I 2 = 90%).…”

“…Seven newly conducted RCTs [15][16][17][18][19][20][21] were identified that were not considered in any of the preceding rereviews [2,23,24,27]. Eleven trials [28][29][30][31][32][33][34][35][36][37] were excluded.…”

“…Figure 7 (cytisine versus placebo, outcome: 1.3, subgroup: income level of study population). The remaining trials[10,12,13,17,19,20] made in upper-/middle-high-income countries (MHICs) deliver a RR of 2.45 (95% CI = 1.48-4.06), with a high level of heterogeneity (I 2 = 81%).Removing the trials rated at high risk of bias from the analysis of the LMICs delivered an RR of 2.38 (95% CI = 0.33-17.34) and increased the I 2 value to 75%. In contrast, removing the trial rated at high risk of bias from the subgroup analysis in MHICs yields an RR of 1.91 (95% CI = 1.40-2.61), with a decrease in the level of heterogeneity (I 2 = 28%).…”