Clinical trial NCT04045964
Conditions: Environmental Tobacco Smoke Smoking Cessation
Sponsor: The University of Texas Health Science Center, Houston
Start date: 2017-10-29; Completion date: 2018-06-28
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to explore the potential for directly targeting smoking cessation, regardless of motivation level, in a subsample of neonatal intensive care unit (NICU) parents with the ultimate goal of reducing secondhand smoke (SHS) in their homes.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: nicotine replacement therapy (NRT) intervention 2: motivational advice intervention 3: Quitline referral
Intervention descriptions: intervention 1: Participants were provided with either 2 weeks of 14-mg or 21-mg transdermal nicotine patches for every smoker in the home intervention 2: Received two in-hospital motivational advice sessions by a research associate (RA). The RA adapted session content from a previous tobacco-smoke exposure protocol intervention 3: Quitline participants received information about tobacco-smoke exposure reduction and a referral to a tobacco Quitline.

Protocol documents:
Prot_SAP_000.pdf: 
IRB NUMBER: HSC-MS-11-0641 
IRB APPROVAL DATE: 09/27/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baby’s Breath II Substudy: Nicotine Patch as an Adjunctive Intervention to Reduce 
Secondhand Smoke Among NICU families 
 
NCT04045964 
 
Version Date: 09/27/2017 
 
 


IRB NUMBER: HSC-MS-11-0641 
IRB APPROVAL DATE: 09/27/2017 
 
Baby’s Breath II Substudy: Nicotine Patch as an Adjunctive Intervention 
to Reduce Secondhand Smoke Among NICU families 
 
 
Aim: In line with our current project aimed to reduce secondhand smoke (SHS) exposure in NICU 
infants’ homes, the aim of the substudy is to evaluate the feasibility and potential efficacy of adding 
nicotine replacement therapy (NRT) in the form of transdermal patches to a motivational intervention 
targeting NICU families who have a smoker in the home. The majority of smoking cessation research is 
conducted with motivated quitters who state a desire to quit. However, a few studies have found that 
providing NRT to unmotivated smokers who are not currently planning to quit was associated with 
positive smoking outcomes [1, 2]. Thus, we would like to explore the potential for directly targeting 
smoking cessation regardless of motivation level in a subsample of NICU parents with the ultimate goal 
of reducing SHS in their homes. 
Hypotheses: (1) Providing NRT as part of a comprehensive secondhand smoke program to NICU families 
will be acceptable and feasible; (2) NRT as part of a comprehensive secondhand smoke intervention will 
increase smoking cessation rates and decrease SHS exposure in homes of NICU families as compared to 
education and referral to a smoking cessation quitline. 
Methods 
Overview. A two group, randomized, controlled substudy (N = 32) will be conducted with parents who 
are smokers and have a high risk, NICU infant. Similar to the parent study, primary caregivers will be 
recruited in the NICU and offered to enroll in the SHS sub-study, including randomization to either 
motivational interviewing and NRT (nicotine patch) or SHS education and referral to a smoking cessation 
quitline. Two follow-up assessments will be conducted 2 weeks and 1 month post-intervention. 
Participants and procedures will largely be the same as the parent study. Altered procedures are noted 
below. 
Participants. Inclusion and Exclusion criteria from the parent study will be retained in this substudy with 
additional criteria related to the provision of NRT noted in red. The nicotine patch is available over-the- 
counter and has been used by the general public with minimal problems. Only extreme disease 
conditions, which should be relatively rare in our population of new, young, parents will be excluded. 
Inclusion Criteria: Eligible mothers of any age or ethnic background must: (1) have an infant that is at 
least 1 week prior to the estimated date of hospital discharge in the NICU at Children’s Memorial 
Hermann Hospital (CMHH; ensuring time for the intervention); (2) report that she or her partner smokes 
at least 5 cigarettes per day, on average, within the 2 months preceding the screening visit; (3) agree to 
attend intervention sessions; (4) live within 50 miles of our center; and (5) have access to a telephone. 
Exclusion Criteria: Mothers will be ineligible for study participation based on the following criteria: (1) 
severe cognitive, and/or psychiatric impairment, per judgment of NICU and research staff, that 
precludes cooperation with study protocol; (2) inability to read, write, and speak English; (3) inability or 
unwillingness to provide signed consent for participation; and (4) inability or unwillingness to meet 
study requirements for data collection and intervention purposes. 
Additional exclusions: 


IRB NUMBER: HSC-MS-11-0641 
IRB APPROVAL DATE: 09/27/2017 
 
• 
Within the month immediately preceding the screening visit, use of any form of tobacco or nicotine 
products other than cigarettes (e.g., e-cigarettes, chewing tobacco, etc.) on 3 or more days within a 
week if the individual refuses to refrain from such tobacco use during the course of the study. 
• 
Current use of NRT or enrollment (or plans to enroll) in another smoking cessation program in the 
next 3 months 
• 
Uncontrolled hypertension (SBP greater than 180 or DBP greater than 110). 
• 
History of severe cardiovascular (stroke, heart attack), kidney (e.g. chronic or acute kidney failure) or 
liver disease, or other unstable disease in the last 3 months. 
• 
History of hypersensitivity or allergic reaction to NRT or similar chemical classes or any component of 
these formulations (including allergy to latex). 
 
Measures. The baseline measures approved for the parent protocol will remain the same. Post 
treatment outcomes also will be largely the same, with a few additions, and will be collected at 2 weeks 
and 1 month post intervention. 
Feasibility/acceptability outcomes. Participants will be asked to report on whether or not any patches 
were used, and if any were used, questions will be asked regarding the # of patches used and 
acceptability and satisfaction with the patch. 
Smoking outcomes will consist of 7-day point prevalence, number of cigarettes smoked per day, number 
of 24 hour quit attempts, and longest sustained abstinence from cigarettes. Similar to the parent study, 
the Timeline Follow-Back [3], a retrospective structured interview, will be used to obtain continuous 
data of actual cigarette consumption in the 30 days prior to study enrollment and will also be used at 
the post intervention timepoints to collect continuous data from the time of intake to the last 
assessment. Parental Exhaled Carbon Monoxide concentration in parts per million will be measured by 
trained personnel using the EC-50 (Vitalograph, Inc., Lenexa, KS), to indicate recent exposure to tobacco 
smoke in parts per million (ppm). These monitors are small, hand-held, battery-operated devices with 
disposable mouthpieces.  Two such instruments purchased for the parent study are currently available 
for use. 
Secondhand smoke outcome measures will include reports of home and car smoking bans and the TLFB 
for secondhand smoke identical to the parent study. 
Intervention. The motivational intervention will be similar to the first two sessions of the parent study 
intervention protocol delivered in the NICU, with additional content related to smoking cessation. In 
addition, parents will be provided with 2 weeks of 21-mg nicotine patches for each smoker (or 14 mg if 
smoking less than 10 cigarettes per day per standard medication instructions 
http://reference.medscape.com/drug/nicoderm-cq-nicotrol-nicotine-transdermal-999319). 
Control. The control condition will receive identical educational materials to the control group in the 
parent study and will also receive a referral to the Texas Tobacco Quitline which provides counseling and 
2 weeks of free nicotine patches after enrollment. 
Sample size estimation 
The primary outcome for this feasibility and preliminary efficacy study is use of the nicotine patch. We 
estimate that 66.7% intervention and 33.3% control participants will use at least one patch during the 


IRB NUMBER: HSC-MS-11-0641 
IRB APPROVAL DATE: 09/27/2017 
 
study period. A sample size of 32 will provide 80% power to detect this effect at the .05 probability 
level. 
Data Analysis 
The general data analytic strategy will be similar to the parent study, using Frequentist and Bayesian 
analyses. Bayesian analyses primarily will be employed to determine the probability of benefit of NRT 
provided directly to smoking parents in the NICU + the behavioral SHS intervention, relative to health 
education and quitline referral. 
Adverse Experiences Associated with Nicotine Replacement Therapy (NRT): All of the commercially 
available forms of nicotine replacement therapy (NRT), i.e. gum, transdermal patch, nasal spray, inhaler, 
lozenge and sublingual tablet, are effective as part of a strategy to promote smoking cessation, 
enhancing long-term abstinence rates as much as 50 to 70%18. Recent reports indicate that 
recommended changes to NRT product labeling by the FDA include a removal of the warning that 
consumers should not use an NRT product if they are still smoking, chewing tobacco, using snuff or any 
other product that contains nicotine—including another NRT. The  FDA suggests to consumers, “There 
are no significant safety concerns associated with using more than one over-the-counter (OTC) NRT at 
the same time, or using an OTC NRT at the same time as another nicotine-containing product—including 
a cigarette” (http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm345087.htm). 
 
In general, the patch is tolerated well by those who use it. The most frequent side effects reported by 
those using the patch tend to be mild and include: nausea, redness at the patch site and/or minor 
swelling, dizziness, difficulty sleeping, rapid heart rate, abnormal dreams, increased blood pressure, 
headaches, rash and/or itching. A review of adverse effects based on 63 trials of 21 mg NRT did not find 
evidence of harm from major adverse cardiovascular events, with a slight increased risk for well-known 
lower-severity events, such as palpitations and arrhythmia [4]. Additionally, a review of safety in 
patients with cardiovascular disease found no evidence of an increased risk of cardiac events [5]. 
Breastfeeding mothers who smoke will not be excluded as the nicotine patch is likely less detrimental 
than smoking cigarettes due to the numerous additional toxins in cigarettes (e.g., carbon monoxide, 
formaldehyde, benzene) [6]. The American Academy of Pediatrics has stated that breastfeeding and 
parental smoking are less detrimental to child health than bottle-feeding and parental smoking, and 
therefore recommend that all mothers breastfeed, regardless of smoking status [7]. Further, data 
suggest that cotinine levels are lower with NRT relative to smoking cigarettes [8]. 
Protection Against Risks: NRT formulations, including the nicotine patch, are FDA approved medications 
for smoking cessation. Our trained research assistants will screen participants for contraindications of 
the nicotine patch and we will monitor participants for adverse reactions while they are on medication. 
Questions regarding safety will be referred to our study physician, Dr. Winston Liaw (recently hired 
Family Medicine faculty member previously on the faculty at Virginia Commonwealth University). 
Potential participants with medical exclusions will be encouraged to see their physicians and obtain 
documented clearance for participation in the study and use of NRT. 
The typical side effects are not usually serious in nature and often abate within a few days to weeks 
after starting medication or once the medication is withdrawn. Adverse effects will be assessed at each 


IRB NUMBER: HSC-MS-11-0641 
IRB APPROVAL DATE: 09/27/2017 
 
of the post-baseline visits. The PI and research staff will monitor participants’ complaints of adverse 
events and, when necessary, adjust the dosage or discontinue medication in consultation with Dr. Liaw. 
Potential Benefits of the Proposed Research to Human Subjects and Others: 
NRT is an evidence-based treatment for nicotine dependence and has been associated with reductions 
in smoking, even among unmotivated smokers. We believe that the proposed research will provide 
preliminary feasibility and efficacy data in support of NRT to increase smoking cessation and reduce SHS 
exposure and health consequences among NICU patients. Participants may benefit directly through 
reduction of the health risks posed by smoking as well as SHS exposure in their children.  Other 
members of participant households may experience similar benefits. The risks posed by SHS in children 
are substantial and well documented, and effective interventions to reduce such exposure in high risk 
infants could result in significant decreases in adverse health effects and associated costs. If successful, 
the proposed intervention could be replicated in other settings that would benefit from evidence-based 
measures to improve the health status of infants and their caregivers. We believe these long-term 
benefits outweigh the risks involved in using NRT and participating in counseling. 
 
 
Role of the Principal Investigator 
 
The Principal Investigator will be responsible for knowing the policies of the local IRB (the University of 
Texas Health Science Center at Houston Committee for the Protection of Human Subjects [CPHS]). The 
PI will adhere to CPHS policies and maintain accurate documentation of CPHS correspondence and 
reports. The PI is responsible for documentation and handling of all possible study-related adverse 
events. These include staff training, manual-driven processes, and periodic audit of data 
collection/entry. 
Data Safeguarding and Checking 
 
Drs. Stotts (PI) and Northrup (Project Director/co-I) will closely monitor the data to ensure participants 
in the study are protected and to ensure their interests are not made secondary to the interests of the 
scientific investigation.  Once a month all key personnel will meet in-person to review study progress 
and address any impediments. Specifically, this team of conscientious investigators will perform the 
following activities:  (a) review the research protocol and plans for data and safety monitoring; (b) 
review major modifications to the study proposed by the team prior to implementation; (c) evaluate 
study progress, including data quality, participant recruitment rates, retention rates, outcome and 
adverse experience data, and risk-versus-benefit profile; (d) communicate information and 
recommendations to appropriate persons at the UTHSC-H IRB regarding the assessment of issues or 
problems and effective resolutions; (e) make recommendations regarding discontinuation of treatment 
for an individual patient based on adverse experiences; (f) make recommendations to terminate the trial 
because of safety concerns; (g) protect the confidentiality of the trial data and the results of monitoring. 
IRB and Adverse Events Reporting. 
 
Adverse Events (AE) will be recorded by study staff as they occur, reported to the PI and CPHS within 24 
hours if determined to be serious. Serious AEs will also be reported immediately (verbally within 24 
hours) to co-investigators, and to the sponsor agency. A written report will follow as soon as possible 
but within no more than three days. The written report will be in the format required by the local IRB 


IRB NUMBER: HSC-MS-11-0641 
IRB APPROVAL DATE: 09/27/2017 
 
and will contain information regarding the date of the SAE, description of the SAE, severity rating (Grade 
1 to 4), assessment of cause, whether the SAE indicates an increased risk for current or future subjects, 
and whether changes to the informed consent form are necessary. 
 
 
References 
1. 
Jardin, B.F., et al., Evaluating the effect of access to free medication to quit smoking: a clinical 
trial testing the role of motivation. Nicotine and Tobacco Research, 2014. 16(7): p. 992-999. 
2. 
Carpenter, M.J., et al., Nicotine therapy sampling to induce quit attempts among smokers 
unmotivated to quit: a randomized clinical trial. Archives of Internal Medicine, 2011. 171(21): p. 
1901-1907. 
3. 
Sobell, L.C., et al., Reliability of alcohol abusers' self-reports of drinking behavior. Behav Res 
Ther, 1979. 17(2): p. 157-60. 
4. 
Mills, E.J., et al., Cardiovascular events associated with smoking cessation pharmacotherapies: a 
network meta-analysis. Circulation, 2013: p. CIRCULATIONAHA. 113.003961. 
5. 
Benowitz, N.L. and S.G. Gourlay, Cardiovascular toxicity of nicotine: implications for nicotine 
replacement therapy. Journal of the American College of Cardiology, 1997. 29(7): p. 1422-1431. 
6. 
Dorea, J.G., Maternal smoking and infant feeding: breastfeeding is better and safer. Maternal 
and Child Health Journal, 2007. 11(3): p. 287-291. 
7. 
AAP-AmericanAcademyofPediatricsCommitteeonDrugs, Transfer of drugs and other chemicals 
into human milk. Pediatrics, 2001. 108: p. 776-789. 
8. 
Bowker, K.A., et al., Comparison of cotinine levels in pregnant women while smoking and when 
using nicotine replacement therapy. Nicotine and Tobacco Research, 2014. 16(6): p. 895-898.