title: Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed.
  
  
  METHODS
  This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect.
  
  
  CONCLUSIONS
  This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN33031001. Registered 27 April 2012.
authors: Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, OX2 6GG Oxford, UK. nicola.lindson-hawley@phc.ox.ac.uk.
authors: Nicola
authors: N
authors: Lindson-Hawley
authors: Tim
authors: T
authors: Coleman
authors: Graeme
authors: G
authors: Docherty
authors: Peter
authors: P
authors: Hajek
authors: Sarah
authors: S
authors: Lewis
authors: Deborah
authors: D
authors: Lycett
authors: Andy
authors: A
authors: McEwen
authors: Hayden
authors: H
authors: McRobbie
authors: Marcus R
authors: MR
authors: Munafò
authors: Steve
authors: S
authors: Parrott
authors: Paul
authors: P
authors: Aveyard
mesh_terms: D002985:Clinical Protocols; D005500:Follow-Up Studies; D006801:Humans; D017063:Outcome Assessment, Health Care; D018401:Sample Size; D016540:Smoking Cessation / Q000379:methods*; D061485:Tobacco Use Cessation Devices