Title: Open-label randomised controlled trial of nicotine replacement therapy (NRT) for preloading, lapse recovery and smoking reduction: impact on smoking in pregnancy
Funder: Department of Health and Social Care

Abstract: BACKGROUND_x000D_ Smoking in pregnancy is harmful to babies and mothers and increases risks of serious complications like miscarriage and stillbirth. It also results in smaller infants being born earlier which can seriously affect their health and development. _x000D_ _x000D_ For healthy babies and mothers, stopping smoking is crucial and the sooner in pregnancy this is achieved the better. Despite trying hard, many women can’t stop or only do so for short periods before smoking again. Although babies are healthiest when pregnant women stop smoking completely, there is strong evidence that if pregnant women cut down their smoking, babies are heavier and healthier than if they had smoked as usual. _x000D_ _x000D_ Nicotine makes cigarettes addictive. Nicotine replacement therapy (NRT) provides nicotine without the many poisons contained in cigarette smoke and, used with advice and tips for quitting, helps pregnant women stop smoking. The NHS tells pregnant women not to smoke ‘even a puff’ but studies suggest that sometimes allowing women to smoke and use NRT together helps with stopping. This study will carefully test whether or not relaxing the ‘not a puff’ rule in 3 different ways helps pregnant women to quit and improves babies’ health._x000D_ _x000D_ AIMS_x000D_ The research will test 3 uses of NRT: _x000D_ _x000D_ Preloading - using patches for a short time when still smoking but preparing to stop. People who ‘preload’ smoke fewer cigarettes and find quitting easier. _x000D_ _x000D_ NRT in ‘slip ups – People trying to stop often ‘slip up’ and smoke occasional cigarettes. Pregnant women who ‘slip up’ are generally advised against using NRT but we will give women very specific advice that they should keep on with NRT during short ‘slip ups’ because doing this may help them carry on quitting and stop smoking for good. _x000D_ _x000D_ Using NRT to cut down – We will ask women who, after a month trying can’t stop smoking, to use NRT to smoke less. When non-pregnant people use NRT like this some end up quitting – even though they didn’t aim to do this and so, using NRT in this way could help pregnant women stop smoking too; if not, breathing in less poisonous cigarette smoke should make babies healthier._x000D_ _x000D_ Interviews with pregnant women who smoke suggest that they are very supportive of these uses of NRT, which women believe could lead to better engagement with and support from stop smoking services._x000D_ _x000D_ _x000D_ METHODS_x000D_ We will recruit 1430 heavier-smoking women from outpatient antenatal settings to a randomised study in which they have equal chance of joining either ‘test’ or ‘control’ groups; both will be offered NHS stop smoking support._x000D_ _x000D_ The test group will also receive advice and help about:_x000D_ 1 An offer of NRT patches to use for up to 4 weeks before a quit date on which they start quitting _x000D_ _x000D_ _x000D_ 2 When quitting, carrying on with NRT during any brief ‘slip-ups’ which involve smoking of occasional cigarettes _x000D_ _x000D_ And, for women who, after one month of trying, can’t stop _x000D_ _x000D_ 3 An offer of patches or fast-acting NRT to help cut down the number of cigarettes smoked_x000D_ _x000D_ We will ask women about smoking later on in their pregnancy and, from hospital notes, will collect information about babies’ birthweight and health. We will also collect information about the costs to the NHS._x000D_ _x000D_ This study could provide new ways for helping pregnant women to stop smoking and, for the first time, for helping women who can’t stop completely, improving their health and their babies’ health.

Lay abstract: DESIGN: Multi-centre, parallel group, open-label RCT _x000D_ _x000D_ PARTICIPANTS: Women of < 25 weeks’ gestation and who smoke > 5 daily cigarettes (> 10 before pregnancy) with exhaled CO readings of > 4ppm_x000D_ _x000D_ SETTING: Hospital antenatal care _x000D_ _x000D_ INCLUSION CRITERIA: As above, agree to set a quit date, accept referral to stop smoking services and willing to use NRT. EXCLUSION: Already in a smoking cessation study, using e-cigarette, contra-indications to NRT._x000D_ _x000D_ CONTROL: Usual care _x000D_ _x000D_ INTERVENTION: NRT used in up to three different ways: _x000D_ _x000D_ i) NRT Preloading – using NRT before a quit date (QD) whilst still smoking instead of starting NRT and attempting abstinence together from a QD onwards._x000D_ _x000D_ ii) Standardised advice to continue NRT during brief smoking lapses occuring after a QD when women use NRT and attempt abstinence_x000D_ _x000D_ And, for women who are still smoking one month after joining the study _x000D_ _x000D_ iii) NRT to reduce smoking and induce cessation_x000D_ _x000D_ PRIMARY OUTCOME: Biochemically-validated, prolonged smoking cessation reported between a quit date and 36 weeks’ gestation with minimal smoking reported at intervening points, consistent with ‘Russell Standard’. _x000D_ _x000D_ SECONDARY OUTCOMES: Birthweight; reported abstinence at 4 weeks post-randomisation and 36 weeks’ gestation; validated 7-day abstinence & exhaled CO at 36 weeks; 50% reduction in daily cigarettes smoked (reported / CO-validated); low birth weight; premature birth; gestation at birth; other birth and neonatal outcomes and use of NHS cessation support._x000D_ _x000D_ SAMPLE SIZE: With a 10% quit rate in the control group and a 5% significance level, a study of 1430 participants (715 per arm) will have 90% power to detect a 6% difference (odds ratio 1.7) in validated cessation rates between the treatment groups. _x000D_ _x000D_ STATISTICS: Trial analysis and reporting will be in accordance with CONSORT guidelines. The primary analysis will use the intention-to-treat population assuming those lost to follow up as smoking. Analysis will use a mixed-effect logistic regression model with a random effect for recruiting site. We will present absolute and relative measures of effect between groups with 95% confidence intervals. Secondary outcomes will be analysed using regression models appropriate to outcome variables._x000D_ _x000D_ ECONOMICS: We will monitor key intervention costs drivers such as, amount of NRT used, time for delivery of support and use of NHS cessation support. We will use an established economic model to conduct an incremental cost-effectiveness analysis with an ‘end-of-pregnancy’ horizon generating ‘cost per quitter’ outcomes and a cost-utility analysis generating incremental costs per QALY with both maternal and infant end of pregnancy and lifetime-horizons. _x000D_ _x000D_ TIMETABLE: Months 1-6: Set-up (site selection, approvals, CRF/database/website development and app revisions); Months 4-8: Site training / initiation; Months 7-15: In-trial pilot, recruit 385 women in 26 centres; Months 16-36: Recruit 1,045 women in 26 centres; End Month 45: last follow-up; Month 44-48: analysis, reporting and dissemination._x000D_ _x000D_ EXPERTISE: Health psychology, economics, smoking cessation, trial design & management, statistics, qualitative research, app development, lay opinion and midwifery. _x000D_ _x000D_ IMPACT: Positive findings could provide new options for using NRT effectively to stop and reduce smoking in pregnancy, protecting infants born to women who cannot stop.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;RESPIRATORY;STROKE