Clinical trial NCT00507975: Study of Nicotine Patch in Pregnancy (SNIPP)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Smoking
Keywords: Smoking
pregnancy
newborn
birth weight
nicotine patch
birth
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2007-07-27
Enrollment: 404
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Continuous and complete smoking abstinence of the pregnant women from the first administration of nicotine/placebo patch until delivery.
timeFrame: from the first administration of nicotine/placebo patch until delivery
Secondary outcomes:
measure: All adverse events occurring during pregnancy
timeFrame: during pregnancy
measure: Point prevalence (7-days) smoking abstinence
timeFrame: 7-days smoking abstinence
measure: Vital signs of the mother and her body weight
timeFrame: during pregnancy
measure: Echography results of the foetus
timeFrame: during the pregnancy
measure: Birth characteristics of the newborn (Apgar, head circumference, height)
timeFrame: at the delivery
measure: Compliance with treatment
timeFrame: during the study
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpétrière, Unité de Recherche Clinique
city: Paris
country: France
facility: Hopital La Pitie Salpetriere
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Ivan BERLIN, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wisborg K, Henriksen TB, Jespersen LB, Secher NJ. Nicotine patches for pregnant smokers: a randomized controlled study. Obstet Gynecol. 2000 Dec;96(6):967-71. doi: 10.1016/s0029-7844(00)01071-1.
citation: Benowitz N, Dempsey D. Pharmacotherapy for smoking cessation during pregnancy. Nicotine Tob Res. 2004 Apr;6 Suppl 2:S189-202. doi: 10.1080/14622200410001669169. No abstract available.
citation: Berlin I, Singleton EG, Heishman SJ. Cross validation of the prognostic and diagnostic utility of tobacco craving in a general and a pregnant sample of treatment-seeking smokers. Drug Alcohol Depend. 2015 Sep 1;154:174-83. doi: 10.1016/j.drugalcdep.2015.06.034. Epub 2015 Jun 29.
citation: Berlin I, Grange G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014 Mar 11;348:g1622. doi: 10.1136/bmj.g1622.