Personalized dosing of nicotine replacement therapy versus standard dosing for the treatment of individuals with tobacco dependence: study protocol for a randomized placebo-controlled trial

Abstract

Background: Medications for smoking cessation are currently only effective in helping a minority of smokers quit. Drug development is slow and expensive; as such, there is much interest in optimizing the effectiveness of existing treatments and medications. Current standard doses of nicotine replacement therapy are not effective for many smokers, and in many cases, the amount of nicotine provided is much less than when a smoker is smoking their usual number of cigarettes. The proposed study will test if titrating the dose of the nicotine patch (up to 84 mg) will improve quitting success compared to those receiving a 21-mg nicotine patch with increasing doses of placebo patch.

Methods: This is a multicenter, pragmatic, two-arm, placebo-controlled, block randomized controlled trial. We will recruit participants who smoke at least 10 cigarettes daily and are interested in making a quit attempt. After 2 weeks of usual treatment with a 21-mg patch, participants who fail to quit smoking (target n = 400) will be randomized to receive escalating doses of a nicotine patch vs matching placebo patches for an additional 10 weeks or up to a maximum dose of 84 mg per day. Those who stop smoking during the first 2 weeks of usual treatment will continue with 21 mg patch treatment for 10 weeks and will form an additional comparison arm. In addition to the medication, participants will receive brief behavioral counseling at each study visit. The primary outcome will be biochemically confirmed continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9 to 12).

Discussion: Research evidence supporting the effectiveness of personalized doses of nicotine replacement therapy could change current practice in a variety of healthcare settings. Given the evidence that quitting smoking at any age diminishes the risk of tobacco-related morbidity and mortality, even small increases in absolute quit rates can have a substantial population-level impact on reducing smoking-related disease, mortality rates, and associated healthcare costs.

Trial registration: ClinicalTrials.gov, NCT03000387 . Registered on 22 December 2016.

Keywords: Dose titration; Nicotine patches; Nicotine replacement therapy; Placebo patches; Smoking cessation.

Fig. 1

Flow diagram of proposed study

Fig. 2

Schedule of enrolment interventions and assessments. ¹Decrease by 7 mg/week—the duration of taper will depend on the dose at week 12; ²Blood for genetics sub-study may be drawn at any week; ³Sitting systolic/diastolic BP, pulse, respiratory rate, and body temperature were measured; ⁴Demographics, readiness, and importance to stop smoking, smoking behaviors; ⁵Urine anabasine (tobacco-specific biomarker) at week 13 (EoT) and urine cotinine at weeks 26 and 52. List of abbreviations: 7-day PPA = 7-day point prevalence abstinence; AUDIT = Alcohol Use Disorders Identification Test; CO = carbon monoxide; CPD = cigarettes per day; DASS 21 = Depression, Anxiety and Stress Scale; DAST-10 = Drug Abuse Screening Test; EoT = end of treatment visit; FTND = Fagerström Test for Nicotine Dependence; IP = in person; mCEQ = cigarette evaluation questionnaire; MNWS = Minnesota Nicotine Withdrawal Scale – validated measure of tobacco withdrawal during cessation treatment; Opt = optional; PHQ-9 = Patient Health Questionnaire—validated self-completed measure of depressive symptoms mapped on to DSM-IV criteria; QSU-brief = 10-item Questionnaire of Smoking Urges; SF-36 = 36-Item Short-Form Health Survey; T = telephone; tNRT = transdermal nicotine replacement therapy