Randomization and trial interventions
Depression, Anxiety, CRF
ADVERSE EVENTS, CRF
Eligible subjects were randomly assigned to either varenicline or placebo in a 1:1 ratio by using a computer-generated, 5-block randomization scheme. Varenicline (0.5 mg tablet) and matched placebo tablets were supplied by Pfizer and randomized by the hospital pharmacy. Participants assigned to varenicline were titrated to full dose by the time of their TQD (0.5 mg/day for 2–3 days, 0.5 mg twice daily for 4–5 days; then 1 mg twice daily for 11 weeks). All subjects in both treatment groups received the same vaping cessation counseling throughout the whole duration of the study. One-on-one counseling was provided at each visit for a total of 10 min by clinical psychologists with experience in nicotine dependence and vaping behaviors. Subjects returned blister cards at each programmed visit and a dosage record was registered.At screening, subjects who reported vaping daily and an intention to quit vaping were assessed for eligibility. Before leaving they were instructed to reduce the average daily vape use by at least 50% before making an appointment to attend the baseline visit (V1).At the baseline visit (V1), eligibility criteria were reassessed and subjects were randomized (1:1) to either varenicline plus vaping cessation counseling or placebo plus vaping cessation counseling. The list for treatment randomization was generated using SAS software (SAS Institute). The size of the blocks was a variable of 5, and the sequence of blocks was randomized and blinded. The following data were recorded at V1: sociodemographic characteristics, medical history, smoking and vaping history (including EC type, e-liquid flavor, and nicotine concentration), and motivation (and reasons) for quitting vaping, vaping/nicotine consumption (assessed by modified Nicotine Use Inventory, mNUI), exhaled carbon monoxide (eCO) levels, blood pressure, heart rate, weight/body mass index (BMI), questionnaires’ scores (Penn State Electronic Cigarette Dependence Index (PSECDI)); Beck Depression Inventory-II (BDI-II)); Beck Anxiety Inventory (BAI)); Minnesota Nicotine Withdrawal Scale (MNWS)), level of motivation to quit vaping (assessed by visual analog score (VAS)), and adverse events. Participants received their first vaping cessation counseling session and were instructed to set a target quit date (TQD) that was within the next 10 days. Prior to check-out, subjects were given a full week’s supply of the assigned treatment (either varenicline or placebo, depending on the treatment arm). Study drugs were dispensed in accordance with the plan (Additional file After V1, subjects were invited to return to the clinic on a weekly basis for the following 12 weeks (V2-V10), except for visits 4, 6, and 8 (telephone contact). At each visit, subjects underwent vaping cessation counseling. Modified NUI, eCO levels, blood pressure, heart rate, weight/BMI (only at Week-12 visit), MNWS (only at week-1, 2, 4, 6, 8, 12 visit), and adverse events were recorded in the CRF at each study visit. At week-4 (V5), week-6 (V7), week-8 (V9), and week-12 (V10), saliva samples were collected for cotinine assessment. Study drugs were dispensed before check-out in accordance with the plan (Additional file The study was continued in the non-treatment follow-up phase after completion of the treatment phase, consisting of a clinic visit at week-24 (V11). Modified NUI, eCO levels, blood pressure, heart rate, weight/BMI, and MNWS were recorded in the CRF at this study visit. Collection of saliva samples was repeated.Saliva samples were collected for cotinine measurement in those who stated they had not vaped and with an eCO ≤ 7 ppm (just to confirm no combustible cigarette use). Participants were asked to chew a small cotton roll (TR0N00RU2, Dentalica, Milano, Italy) for 60 s. Cotton rolls were placed into polypropylene tubes and stored at − 20 °C until use. Cotinine concentrations in saliva samples were analyzed in duplicate by gas chromatography [