Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes: The ORCA-V1 Randomized Clinical Trial

Abstract

Importance: The prevalence of e-cigarette use among US adults, especially young adults, is rising. Many would like to quit vaping nicotine but are unable to do so. Cytisinicline, a plant-based alkaloid, targets nicotinic acetylcholine receptors, reduces nicotine dependence, and helps adults to stop smoking cigarettes. Cytisinicline may also help e-cigarette users to quit vaping.

Objective: To determine the efficacy and safety of cytisinicline vs placebo to produce abstinence from e-cigarette use in adults seeking to quit vaping nicotine.

Design, setting, and participants: This double-blind placebo-controlled randomized clinical trial compared 12 weeks of treatment with cytisinicline vs placebo, with follow-up to 16 weeks. It was conducted from July 2022 to February 2023 across 5 US clinical trial sites. A total of 160 adults who vaped nicotine daily, sought to quit, and did not currently smoke cigarettes were enrolled, and 131 (81.9%) completed the trial.

Intervention: Participants were randomized (2:1) to cytisinicline, 3 mg, taken 3 times daily (n = 107) or placebo (n = 53) for 12 weeks. All participants received weekly behavioral support.

Main outcomes and measures: Biochemically verified continuous e-cigarette abstinence during the last 4 weeks of treatment (weeks 9-12; primary outcome) and through 4 weeks posttreatment (weeks 9-16; secondary outcome). Missing outcomes were counted as nonabstinence.

Results: Of 160 randomized participants (mean [SD] age, 33.6 [11.1] years; 83 [51.9%] female), 115 (71.9%) formerly smoked (≥100 lifetime cigarettes). Continuous e-cigarette abstinence in cytisinicline and placebo groups occurred in 34 of 107 participants (31.8%) vs 8 of 53 participants (15.1%) (odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04) at end of treatment (weeks 9-12) and in 25 of 107 participants (23.4%) vs 7 of 53 participants (13.2%) during weeks 9 to 16 (odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). There was no evidence, based on nonsignificant interactions, that cytisinicline efficacy differed in subgroups defined by demographic characteristics, vaping pattern, e-cigarette dependence, or smoking history. Cytisinicline was well tolerated, with 4 participants (3.8%) discontinuing cytisinicline due to an adverse event.

Conclusions and relevance: In this randomized clinical trial, cytisinicline for 12 weeks, with behavioral support, demonstrated efficacy for cessation of e-cigarette use at end of treatment and was well tolerated by adults, offering a potential pharmacotherapy option for treating nicotine e-cigarette use in adults who seek to quit vaping. These results need confirmation in a larger trial with longer follow-up.

Trial registration: ClinicalTrials.gov Identifier: NCT05431387.

Figure 1.. CONSORT Diagram

Figure 2.. Other Measures of Treatment Effectiveness During and After Treatment

A, At each week, participants reported whether they had used an e-cigarette in the past 7 days (or since the last visit at week 16). A participant was classified as abstinent for that week if no e-cigarette use was reported and was biochemically confirmed. Missing assessments were classified as nonabstinent to include all randomized. The prevalence probabilities and exact 95% CIs (error bars) were estimated at each week. B, Saliva cotinine samples were collected at each week during treatment and at 16-week follow-up. The figure compares the saliva cotinine values of 157 participants randomized to cytisinicline (n = 105) or placebo (n = 52). Circles represent mean values at each week. Diamonds represent median values. Numbers below the x-axis indicate the number of participants in each randomized group who contributed data for analysis at each visit. The cotinine assay has a lower limit of detection of 1 ng/mL, and the figure illustrates that after randomization, materially more participants in the cytisinicline group had assay results below the limit of detection.