Official Title: “Assessment of the Effectiveness of Nicotine Replacement Therapies (Nicotine Patches Delivering Nicotine 16 h/24 h) in 400 Pregnant Smokers. Randomized, Placebo-Controlled, Multicenter, National Study. The SNIPP.”

There are no established evidences as to the effectiveness in smoking pregnant women of nicotine patches in increasing birth weight, smoking abstinence during pregnancy and concerning the safety their for the fetus/newborn. Moreover, recent studies have shown that the metabolism of nicotine is speeded up in pregnant women suggesting that dose adaptation may be necessary in this population. The main aim of this study is to assess the effectiveness of nicotine patch comparatively to a placebo patch in pregnant women on birth weight and maternal smoking abstinence. The main secondary objective is the assessment of safety of these treatments for the fetus/newborn and for the mother.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2011

Smoking during pregnancy is one of the main causes of low birth weight and several disorders during pregnancy involving the mother, the fetus/newborn or both. Only one previous study assessed the efficacy of 16 hours nicotine patch proposed for 3 months in pregnant women for smoking cessation. This study seemed to be underpowered and the compliance was very poor.

However, some benefit on birth weight was observed.

The aim of the present study is to demonstrate whether nicotine replacement therapy with 16 h nicotine patch every day increases or not birth weight and abstinence during pregnancy in smoking women. Secondarily, it is aimed to provide descriptive information about the safety of nicotine patches in pregnant women.

This is a double blind, randomized, placebo controlled study. With 200 pregnant women in each arm it will have sufficient power to conclude about differences in birth weight and maternal abstinence between nicotine and placebo.

Women are recruited by health care professionals and directed to the obstetrical departments having previously been agreed to participate in the study.

After a grace period of one month without pharmacological treatment, the pregnant women are randomized into the placebo (N=200) or the nicotine group (N=200). Treatment duration is from randomization till delivery meaning a maximum length of drug/placebo exposure of 6 month during pregnancy. No treatment is started earlier than 3 months' pregnancy. Women may optionally continue their treatment for at least up to 2 months after birth.

At the inclusion visit when the women are smoking, saliva cotinine is collected and determined. The first dose of nicotine is adapted according to the saliva cotinine when smoking to obtain approximately 100 % substitution. A second saliva cotinine determination is realized 2 weeks later and at the next visit nicotine's daily dose is determined according to this second saliva cotinine results for the whole duration of pregnancy. This dose-adaptation is necessary to avoid as far as possible under- and overdosing of nicotine.

The women undergo monthly visits as it is usual and recommended in France. They are followed as well as their newborn up to 2 months after birth.

During the visits standard obstetrical information along with smoking related information and the routinely realized echography data are recorded and birth characteristics collected.

In a subgroup of pregnant women having given their written informed consent and undergoing an amniocentesis for medical reasons, nicotine and cotinine in amniotic fluid will be determined.

In a subgroup of pregnant women having given their written informed consent and breast feeding their baby during the 2 months period after birth, nicotine and cotinine in maternal milk are determined.

There are 2 main outcome comparisons between the nicotine patch and the placebo patch groups:

birth weight and maternal continuous, complete abstinence during pregnancy

Intervention(s) in this Clinical Trial

• Drug: nicotine versus placebo
  • The main aim of this study is to assess the effectiveness of nicotine patch comparatively to a placebo patch in pregnant women on birth weight and maternal smoking abstinence. The main secondary objective is the assessment of safety of these treatments for the fetus/newborn and for the mother.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: A
  • The main aim of this study is to assess the effectiveness of nicotine patch comparatively to a placebo patch in pregnant women on birth weight and maternal smoking abstinence. The main secondary objective is the assessment of safety of these treatments for the fetus/newborn and for the mother.
• Experimental: B
  • The main aim of this study is to assess the effectiveness of nicotine patch comparatively to a placebo patch in pregnant women on birth weight and maternal smoking abstinence. The main secondary objective is the assessment of safety of these treatments for the fetus/newborn and for the mother.

Primary Measures

• Continuous and complete smoking abstinence of the pregnant women from the first administration of nicotine/placebo patch until delivery.
  • Time Frame: from the first administration of nicotine/placebo patch until delivery
    Safety Issue?: No

Secondary Measures

• All adverse events occurring during pregnancy
  • Time Frame: during pregnancy
    Safety Issue?: Yes
• Point prevalence (7-days) smoking abstinence
  • Time Frame: 7-days smoking abstinence
    Safety Issue?: No
• Vital signs of the mother and her body weight
  • Time Frame: during pregnancy
    Safety Issue?: Yes
• Echography results of the foetus
  • Time Frame: during the pregnancy
    Safety Issue?: Yes
• Birth characteristics of the newborn (Apgar, head circumference, height)
  • Time Frame: at the delivery
    Safety Issue?: Yes
• Compliance with treatment
  • Time Frame: during the study
    Safety Issue?: Yes

Inclusion Criteria:

• smoking pregnant woman unable to quit smoking during the first 3 months of pregnancy
• smoking ≥ 5 cigaret/day despite standard medical advice and cognitive-behavioral counselling
• aged ≥ 18 years
• health insured
• motivated to stop smoking; motivation score ≥ 5 on a scale ranging from 0 to 10
• amenorrhea of 9 to 20 weeks
• having signed the written informed consent

Exclusion Criteria:

• non-pregnant women
• men

Pregnant woman:

• who does not agree to use a nicotine or placebo patch
• with presence of chronic psychiatric comorbidity treated continuously by antidepressant, neuroleptic or anxiolytic
• with skin disorder contraindicating the use of a transdermal patch
• with known hypersensitivity to transdermal patch or to one of its constituents
• using other nicotine containing pharmaceutical products (gum, lozenge, inhaler, sublingual tablets)
• using other forms of tobacco than cigaret (cigaret, pipe or any form of smokeless tobacco)

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

Ivan BERLIN, MD,PhD Principal Investigator Assistance Publique - Hôpitaux de Paris  

Overall Contact: Ivan BERLIN, MD,PhD +33(0) 1 42 16 16 78 ivan.berlin@psl.aphp.fr

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00507975

Study ID Number: P060604

ClinicalTrials.gov Identifier: NCT00507975

Health Authority: France: Ministry of Health