Nakamura 2007
| Methods | Country: Japan Setting: 19 study sites Aim: To test efficacy, safety and tolerability of 3 doses of varenicline over 12 wks Dates conducted: not stated Study Design: Double‐blind, placebo‐controlled, parallel group RCT Analysis: Power calculation (90%, alpha = 0.05) for 0.5 or 1.0 mg vs placebo; ITT denominators; also logistic regression (step‐down) with dose and study centre as categorical variables |
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| Participants | 619 healthy Japanese adult volunteers, aged 20 ‐ 75, smoking ≥ 10 CPD. Allocated to varenicline 0.25 mg x 2/day (153), 0.5 mg x 2/day (156), 1.0 mg x 2/day (156) or placebo x 2/day (154). 1 participant withdrew before treatment, and is excluded from ITT denominator. 1 RTA death removed from varenicline group at 52 wks Participants stratified by level of nicotine dependence, measured by Tobacco Dependence Screener scale (≥ 5) and by FTND. 515 (83.3%) classified as nicotine dependent Demographic data only supplied for nicotine‐dependent group (515/618): 75% men, mean age 39.8, mean CPD 24, mean FTND score 5.6 Exclusion criteria: Standard pharmacotherapy trial criteria, + use of NRT within last 30 days, use of pipe tobacco, snuff, chewing tobacco, cigars within last 30 days and throughout trial | |
| Interventions | 1. Varenicline 0.25 mg x 2/day 2. Varenicline 0.50 mg x 2/day 3. Varenicline 1.00 mg x 2/day 4. Placebo tablet x 2/day Treatment period 12 wks, 1st wk titrated dosage. All participants received a smoking cessation booklet Clearing the Air at baseline, + brief counselling (≤ 10 mins) at each clinic visit. Weekly visits throughout treatment phase, plus a 5‐min phone call at TQD and +3 days post‐TQD In follow‐up phase, clinic visits at wks 13, 16, 24, 36, 44 and 52, plus brief phone calls at wks 20, 28, 32, 40 and 48 | |
| Outcomes | Primary outcome: CO‐validated CAR at 9 ‐ 12 wks Secondary outcomes: CO‐validated CAR at 9 ‐ 24 wks and 9 ‐ 52 wks; 7‐day PPA at wks 2, 12, 24 and 52 Validation was by expired CO ≤ 10 ppm Other outcomes: Withdrawal symptoms (using MNWS, QSU‐brief and mCEQ), adverse events Dropouts and losses to follow‐up were included in the analyses as continuing smokers (ITT analysis) Attrition in treatment phase was 6.4%, losses to follow‐up 11.4% of treatment completers (excluding 1 death) | |
| Treatment type | Medication: VARENICLINE | |
| Notes | Trial was funded by Pfizer Inc New for 2008 update | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "computer‐generated list of random numbers" |
| Allocation concealment (selection bias) | Low risk | "randomized to 1 of the 4 treatment groups in a 1:1:1:1 ratio using a central procedure" |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "double‐blinding of subjects and investigators was maintained throughout the study". |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No comment on level or handling of missing data |
| Selective reporting (reporting bias) | High risk | CARs for all participants reported, but demographics, withdrawal and craving measures, and PPA for nicotine‐dependent group only |
| Other bias | Unclear risk | None noted |