Tonstad 2006
| Methods | Country: USA (6 centres) and 'international' (18 centres, across Canada, Czech Republic, Denmark, Norway, Sweden, UK*) Setting: 24 research centres Aim: To test the efficacy and safety of extended varenicline treatment for preventing relapse in adults who have quit smoking on open‐label varenicline Dates conducted: April 2003 ‐ February 2004 (initial recruitment phase) Study Design: Double‐blind placebo‐controlled RCT. Analysis: Power calculation (80%, alpha = 0.05); ITT denominators and logistic regression analysis for binary data, and Kaplan‐Meier curve for time to first lapse |
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| Participants | 1210 successful quitters (62.8% of initial cohort) following a 12‐wk open‐label course of varenicline for smoking cessation, randomised to varenicline (603) or placebo (607) for a further 12 wks. 49% men, 97% white, mean age 45, BMI < 15 or > 38 or weight < 45.5 kg, mean CPD 21, mean FTND score 5.4 Exclusion criteria: Standard pharmacotherapy trial criteria, + use of marijuana or tobacco products other than cigarettes within last month; use of NRT, bupropion, clonidine, nortriptyline within last month | |
| Interventions | 1. Varenicline 1 mg x 2/day for 11 wks after 1 wk titrated dosage 2. Placebo tablets, same regimen All participants also received brief counselling (≤ 10 mins) at each clinic visit throughout treatment phase (wks 13 ‐ 24). Treatment phase clinic visits were at wks 13, 14, 16, 20 and 24 Follow‐up phase: 5 visits and 4 phone calls from wks 25 ‐ 52 | |
| Outcomes | Primary outcome: Relapse prevention: maintenance of CO‐validated CAR at 24 wks Secondary outcome: CO‐validated CAR at wk 52; 7‐day PPA at wks 24 and 52. 2 deaths removed from varenicline denominator at 52 wks Other outcomes: weight change, withdrawal symptoms (using MNWS), time to first lapse, adverse events Validation was by expired CO ≤ 10 ppm Dropouts and losses to follow‐up were included in the analyses as continuing smokers (ITT analysis) Attrition was 12% during treatment phase, and 10% of treatment completers lost during follow‐up phase | |
| Treatment type | Medication: VARENICLINE | |
| Notes | * additional information supplied by author The trial was funded by Pfizer Inc | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "computer‐generated randomization sequence (stratified by center with a block size of 4)" |
| Allocation concealment (selection bias) | Low risk | "a single, centralised [system]" |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "double‐blind treatment phase"; "participant blinding was maintained during this [non‐treatment follow‐up] phase" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Missing COs were considered abstinent if other criteria OK; at wk 52 all criteria had to be met |
| Selective reporting (reporting bias) | Low risk | All expected and predicted outcomes covered |
| Other bias | Unclear risk | None noted |