Williams 2007
| Methods | Country: USA and Australia Setting: 9 research centres (8 USA, 1 Aus) Aim: To test the safety of long‐term (12m) use of varenicline in smokers trying to quit Study Design: Double‐blind placebo‐controlled RCT Dates conducted: October 2003 ‐ March 2005 |
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| Participants | 377 adult smokers, aged 18 ‐ 75, smoking at least 10 CPD. 49.9% men, 88.6% white, av CPD at baseline 23, mean FTND 5.5 in treatment group, 6.05 in control group. Allocated to varenicline (251) or placebo (126) Exclusion criteria: Standard pharmacotherapy trial criteria, + no use of NRT, antidepressants, antipsychotics, naltrexone during study period. | |
| Interventions | 1. Varenicline 1mg x 2/day, titrated for first wk 2. Placebo inactive tablets, same regimen All participants received S‐H booklet Clearing the Air. Brief counselling (≤ 10 mins) at each visit TQD was 1st day of wk 1 visit (7 ‐ 10 days post‐randomisation) Treatment period was 52 wks. Weekly visits throughout wks 1 ‐ 8, then every 4 wks to wk 52, + wk 53 assessment Blood and urine samples taken at screening, baseline, wks 2, 12, 24, 36, 52 (or early termination) Complete physical exam at baseline, wks 24 and 52; BP, pulse and weight measured at all visits, ECG at screening, baseline, wks 2, 24 and 52 (or early termination) | |
| Outcomes | Primary outcome: Safety of smokers treated continuously with varenicline over 52 wks, measured at wk 53 by level and tolerability of adverse events and incidence of SAEs Secondary outcome: 7‐day CO‐verified PPA at all clinic visits (expired CO ≤ 10 ppm) Other outcomes: Weight change; changes in vital signs Attrition was 46.2% in varenicline group, 53.2% in control group by end of study | |
| Treatment type | Medication: VARENICLINE | |
| Notes | This was a safety study, with cessation rates collected as a secondary outcome The trial was funded and conducted by Pfizer Inc In the first version of this review, this trial appeared as Reeves 2006 (unpublished data) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation 2:1 varenicline to placebo. No detailed information reported |
| Allocation concealment (selection bias) | Unclear risk | No information reported |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | No information reported |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Missing CO and/or visit taken as smokers |
| Selective reporting (reporting bias) | Low risk | Primary outcome was safety, so minimal cessation data |
| Other bias | Unclear risk | None noted |