The ORCA-VI (Ongoing Research of Cytisine for Addiction) randomized clinical trial aimed to evaluate the efficacy and safety of cytisinicline, a plant-based alkaloid, in helping adults who vape nicotine to quit. The study involved 160 participants who were randomized to receive either cytisinicline (3 mg, 3 times daily) or a placebo for 12 weeks, with follow-up for 16 weeks. The primary outcome was biochemically verified continuous e-cigarette abstinence during the last 4 weeks of treatment (weeks 9-12), and secondary outcomes included abstinence through 4 weeks post-treatment (weeks 9-16). Key findings include: - Cytisinicline significantly increased the odds of achieving continuous e-cigarette abstinence compared to placebo (odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). - The treatment was well tolerated, with only 3.8% of participants discontinuing due to adverse events. - Secondary outcomes showed similar trends but were not statistically significant. - No significant differences in efficacy were observed across subgroups defined by demographic characteristics, vaping patterns, or smoking history. The study concluded that cytisinicline, combined with behavioral support, is a promising pharmacotherapy for helping adults quit vaping nicotine, offering a potential new treatment option. However, larger trials with longer follow-up are needed to confirm these findings.The ORCA-VI (Ongoing Research of Cytisine for Addiction) randomized clinical trial aimed to evaluate the efficacy and safety of cytisinicline, a plant-based alkaloid, in helping adults who vape nicotine to quit. The study involved 160 participants who were randomized to receive either cytisinicline (3 mg, 3 times daily) or a placebo for 12 weeks, with follow-up for 16 weeks. The primary outcome was biochemically verified continuous e-cigarette abstinence during the last 4 weeks of treatment (weeks 9-12), and secondary outcomes included abstinence through 4 weeks post-treatment (weeks 9-16). Key findings include: - Cytisinicline significantly increased the odds of achieving continuous e-cigarette abstinence compared to placebo (odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). - The treatment was well tolerated, with only 3.8% of participants discontinuing due to adverse events. - Secondary outcomes showed similar trends but were not statistically significant. - No significant differences in efficacy were observed across subgroups defined by demographic characteristics, vaping patterns, or smoking history. The study concluded that cytisinicline, combined with behavioral support, is a promising pharmacotherapy for helping adults quit vaping nicotine, offering a potential new treatment option. However, larger trials with longer follow-up are needed to confirm these findings.