Effects on abstinence of nicotine patch treatment before quitting smoking: parallel, two arm, pragmatic randomised trial

The Preloading Investigators

Research output: Contribution to journalArticle (Academic Journal)


To examine the effectiveness of a nicotine patch worn
for four weeks before a quit attempt.
Randomised controlled open label trial.
Primary care and smoking cessation clinics in
England, 2012-15.
1792 adults who were daily smokers with tobacco
dependence. 899 were allocated to the preloading
arm and 893 to the control arm.
Participants were randomised 1:1, using concealed
randomly permuted blocks stratified by centre, to
either standard smoking cessation pharmacotherapy
and behavioural support or the same treatment
supplemented by four weeks of 21 mg nicotine patch
use before quitting: “preloading.”
Main outcome measures
The primary outcome was biochemically confirmed
prolonged abstinence at six months. Secondary
outcomes were prolonged abstinence at four weeks
and 12 months.
Biochemically validated abstinence at six months
was achieved by 157/899 (17.5%) participants in the
preloading arm and 129/893 (14.4%) in the control
arm: difference 3.0% (95% confidence interval −0.4%
to 6.4%), odds ratio 1.25 (95% confidence interval
0.97 to 1.62), P=0.08 in the primary analysis. There
was an imbalance between arms in the frequency
of varenicline use as post-cessation treatment, and
planned adjustment for this gave an odds ratio for
the effect of preloading of 1.34 (95% confidence
interval 1.03 to 1.73), P=0.03: difference 3.8% (0.4%
to 7.2%). At four weeks, the difference in prolonged
abstinence unadjusted for varenicline use was odds
ratio 1.21 (1.00 to 1.48), difference 4.3% (0.0% to
8.7%), P=0.05, and adjusted for varenicline use was
1.32 (1.08 to 1.62) P=0.007. At 12 months the odds
ratio was 1.28 (0.97 to 1.69), difference 2.7% (−0.4%
to 5.8%), P=0.09 unadjusted for varenicline use and
after adjustment was 1.36 (1.02 to 1.80) P=0.04.
5.9% of participants discontinued preloading owing
to intolerance. Gastrointestinal symptoms—chiefly
nausea—occurred in 4.0% (2.2% to 5.9%) more
people in the preloading arm than control arm. Eight
serious adverse events occurred in the preloading arm
and eight in the control arm (odds ratio 0.99, 0.36 to
Evidence was insufficient to confidently show that
nicotine preloading increases subsequent smoking
abstinence. The beneficial effect seems to have
been masked by a concurrent reduction in the use of
varenicline in people using nicotine preloading, and
future studies should explore ways to mitigate this
unintended effect.
Original languageEnglish
Pages (from-to)1
Number of pages11
Publication statusPublished - 30 Apr 2018

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