Double-blind, randomised, placebo-controlled trial of nicotine replacement therapy in pregnancy

ISRCTN	ISRCTN07249128
DOI	https://doi.org/10.1186/ISRCTN07249128
Protocol serial number	HTA 06/07/01
Sponsor	University of Nottingham (UK)
Funder	Health Technology Assessment Programme

Submission date: 03/05/2005
Registration date: 21/06/2005
Last edited: 12/05/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Women are highly motivated to stop smoking in pregnancy. Nicotine replacement therapy (NRT) is a medically-approved way to take nicotine by means other than tobacco, to help the patient stop smoking. The aim of this study is to assess the effectiveness and cost effectiveness of nicotine replacement therapy during pregnancy, and to find out whether it has any effect on children’s behaviour and cognitive development at two years of age.

Who can participate?
Women who are between 12 and 24 weeks pregnant and who smoke at least five cigarettes daily

What does the study involve?
Participants are randomly allocated to receive an eight-week course of NRT patches or placebo (dummy) patches. Participants also receive individual behavioural support. Four weeks after their quit dates, women who are not smoking are issued with a second four-week supply of patches.

What are the possible benefits and risks of participating?
If NRT is demonstrated to be effective and safe in pregnancy, more pregnant smokers will use NRT whilst they are pregnant. This will increase the number of women who successfully stop smoking during pregnancy and will improve women's health. Reducing smoking during pregnancy will, in turn, lower the incidence of miscarriage, stillbirth and low birth weight. Smoking in pregnancy is also associated with childhood illness including an increased risk of asthma, sudden infant death syndrome and learning problems, so reducing smoking is likely to decrease the frequency of these problems. Finally, it is recognised that teenagers are more likely to initiate smoking if their parents smoke. Consequently, reducing smoking in pregnancy is likely to cause longer term reductions in smoking by young people.

Where is the study run from?
University of Nottingham (UK)

When is the study starting and how long is it expected to run for?
February 2006 to November 2012

Who is funding the study?
Health Technology Assessment Programme (UK)

Who is the main contact?
Sue Cooper
sue.cooper@nottingham.ac.uk

Contact information

Ms Sue Cooper
Scientific

SNAP Trial Office
University of Nottingham
Academic Division of Obstetrics & Gynaecology
City Hospital Maternity Unit
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Phone	+44 (0)115 823 1898
Email	sue.cooper@nottingham.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Double-blind, randomised, placebo-controlled trial of nicotine replacement therapy in pregnancy (SNAP)
Study acronym	SNAP
Study objectives	1. To compare at delivery: the effectiveness and cost effectiveness for achieving biochemically-validated smoking cessation of nicotine replacement therapy and placebo patches in pregnancy 2. To compare at two years after delivery: the effects of maternal nicotine replacement therapy and placebo patch use in pregnancy on behaviour and cognitive development in children More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/060701 Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0017/51290/PRO-06-07-01.pdf
Ethics approval(s)	Oxfordshire REC A ethics committee, ID number 04/Q1604/85
Health condition(s) or problem(s) studied	Pregnancy/Childbirth
Intervention	Treatment group: Pregnant women will receive an eight week course of 15 mg/16 hour NRT transdermal patches. Although many studies have used longer courses, there is no evidence that these are more effective. Patches will be issued in conjunction with individual behavioural support which is an effective smoking cessation intervention in pregnancy. Four weeks after their quit dates, women who are not smoking will be issued with a second four week supply of patches. Control group: Women in the control arm of the trial will receive an identical placebo NRT patch and the same behavioural support as those in the treatment group. In both control and intervention groups, participants will be blind to their group allocation.
Intervention type	Other
Primary outcome measure(s)	Self-reported, prolonged and total abstinence from smoking or the use of any non-pharmacological nicotine containing substances between a quit date set within two weeks of randomisation and immediately prior to childbirth. Prolonged abstinence cannot be comprehensively validated, but if participants report prolonged abstinence and are abstinent at both time points below, they will be considered to have a positive primary outcome: 1. Self reported smoking cessation for at least 24 hours before follow-up at one month after quit date, validated by exhaled Carbon Monoxide measurement 2. Self reported smoking cessation for at least 24 hours before hospital admission for childbirth, validated by exhaled Carbon Monoxide or salivary cotinine measurement
Key secondary outcome measure(s)	1. Smoking: 1.1. Self reported, prolonged abstinence from smoking between quit date and one month 1.2. Self reported, prolonged abstinence from smoking between quit date and 6 months after delivery 1.3. Self reported smoking cessation for previous 7 day period at 6 months after delivery (point prevalence) 1.4. Self reported, prolonged abstinence from smoking between quit date and 2 years after delivery 1.5. Self reported smoking cessation for previous 7 day period at 2 years after delivery (point prevalence) 2. Foetal loss and morbidity: 2.1. Foetal death and stillbirth 2.2. Neonatal death (i.e. from birth to 28 days) 2.3. Post-neonatal death (29 days to 2 years) 2.4. Individualised birth weight Z score (i.e. birth weight adjust for gestational age, maternal height, maternal weight at booking and ethnic group) 2.5. Apgar score 2.6. Cord blood pH 2.7. Gestational age at birth 2.8. Intraventricular haemorrhage 2.9. Neonatal enterocolitis 2.10. Neonatal convulsions 2.11. Congenital abnormality 3. Maternal morbidity and mortality: 3.1. Maternal mortality 3.2. Mode of delivery 3.3. Proteinuria 3.4. Hypertension in pregnancy 4. Early childhood outcomes: 4.1. Behaviour and development at 2 years 4.2. Disability at 2 years 4.3. Respiratory symptoms at 2 years 5. Health economic data: 5.1. Duration of maternal hospital admission for childbirth 5.2. Duration of any admission (of baby) to special care 5.3. Health status at 6 months (EQ5D)
Completion date	30/11/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	1050
Key inclusion criteria	1. Eligible women are women between 12 and 24 weeks pregnant 2. Report smoking at least ten cigarettes daily before pregnancy 3. Still currently smoke at least five cigarettes daily 4. An exhaled Carbon Monoxide (CO) reading above 8 ppm
Key exclusion criteria	Women with the following contraindications to the use of NRT will be excluded: 1. Severe cardiovascular disease 2. Unstable angina 3. Cardiac arrhythmias 4. Recent cerebrovascular accident or Transient Ischaemic Attack (TIA) 5. Chronic generalised skin disorders or known sensitivity to nicotine patches 6. Chemical dependence/alcohol addiction problems 7. Women who cannot give informed consent and those with known major foetal anomalies will also be excluded Intra-Uterine Growth Restriction (IUGR) is not an exclusion criterion.
Date of first enrolment	01/02/2006
Date of final enrolment	30/11/2012

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University of Nottingham

Nottingham
NG5 1PB
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/03/2012		Yes	No
Results article	results	01/06/2014		Yes	No
Results article	results	01/08/2014		Yes	No
Results article	follow-up results	01/09/2014		Yes	No
Protocol article	protocol	03/01/2007		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

12/05/2016: Plain English summary added.

11/05/2009: the overall trial end date has been changed from 31/01/2012 to 30/11/2012.