Clinical trial NCT02859142
Conditions: Smoking Cessation Alcohol Drinking
Keywords: Varenicline
Sponsor: University of Chicago
Start date: 2018-03-29; Completion date: 2020-10-15
Enrollment: 122 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to learn if the combination of a study drug and patch is more effective in helping heavy drinkers stop smoking than just the patch alone The study drug, varenicline, has been approved by the Food and Drug Administration (FDA) to help people stop smoking, but it is not known if the addition of varenicline to standard smoking cessation treatment with nicotine patches will help people stop smoking who are regular, frequent drinkers. This study is being done because cigarette smoking is the number one preventable cause of death and disease in the United States.

Detailed description:
This study will conduct a real-world clinic-based smoking cessation trial examining the augmentation strategy of Chantix (Varenicline Tartrate), nicotine patch, and behavioral counseling versus standard treatment of patch plus behavioral counseling only in heavy drinkers who smoke (HDS). While Chantix is approved for smoking cessation, it is not routinely given in practice for HDS patients

In this study, there will be 4 total in-person study visits over the trial (pre-quit, quit date, week 2 and week 12), ending 12 weeks after the quit date. Biochemical verification from breath tests for CO, as well as vital signs and weight, will be measured at each visit along with survey responses measuring smoking urge and withdrawal, negative affect, neurocognition, and alcohol and smoking behaviors. These will also be used at a 26-week follow-up by telephone with biochemical verification for CO in those reporting being smoke-free.

Screening and Randomization Participants will respond to advertisements and will undergo a brief phone screening to determine initial eligibility requirements. Qualified candidates will be invited into the lab to conduct a short screening and study information session at the Clinical Addictions Research Laboratory at the University of Chicago. At screening, participants will sign an informed consent document. Next, demographics, smoking, alcohol and substance use patterns, health history, medications, vital signs, a urine test (for pregnancy and/or drug toxicology) and a blood test will be obtained.

Eligible participants will be randomized into one of two treatment groups: Standard Treatment (w/ placebo) will proceed with the study receiving nicotine patches and brief counseling sessions; Augmented Treatment will proceed with the same nicotine patches and brief counseling sessions, but will also receive standard dosing of Chantix (Varenicline tartrate).

Nicotine Patches Nicotine patches will be utilized starting at study quit date, and proceed according to package insert directions (10+ cigs/day smokers will begin with 21mg patches for six weeks, followed by 14mg patches for four weeks, and finally 7mg patches for two weeks. Those smoking fewer than 10 cigarettes/day will follow the same process starting at the 14mg patch level.

Chantix (Varenicline Tartrate) Those receiving Augmented Treatment will receive varenicline. They will undergo an up-titration week prior to the quit date, 12 weeks of target dosing, and a down-titration week. As per Pfizer recommendations, up-titration will be 0.5mg tablets once daily for 3 days followed by twice daily for four days leading to the quit date on day 8. The sequence will reverse for a down-titration week on week 13.

Placebo for Varenicline Those receiving standard treatment will also receive placebo medication that will be identical in appearance to and follow the same distribution protocol as varenicline.

Smoking Cessation Behavioral Sessions:

Participants will attend one-on-one behavioral counseling sessions with a trained Masters or PhD. Level therapist at each study visit. Behavioral sessions will involve teaching behavioral skills to assist with smoking cessation, preventing relapse, and coping with physical or emotional changes associated with cravings. At each study visit, subjective measures (i.e. brief self-report surveys about

Follow-Up Interview (Week 26) At Study Week 26, participants will complete a follow-up telephone interview, completing similar subjective measures as those completed during study visits. Participants reporting being smoke-free during this interview will arrange for biochemical verification of this status via expired CO testing either by arranging for a time to stop into one of the study sites or by arranging for study staff to meet with them in their home or workplace.

Arms: arm 1: Participants receive 12 weeks of Chantix along with standard smoking cessation treatment of nicotine patches and behavioral counseling visits.

* Chantix (Varenicline) and NicodermCQ (Nicotine Patches): Administered according to package insert directions
* Behavioral Counseling Sessions: Participants will attend one-on-one behavioral counseling sessions with a trained therapist at each of 4 study visits (pre-quit, quit date, week 2, and week 12). Behavioral sessions will involve teaching behavioral skills to assist with smoking cessation, preventing relapse, and coping with physical or emotional changes associated with cravings. arm 2: Participants receive 12 weeks of standard smoking cessation treatment of nicotine patches and behavioral counseling visits in addition to placebo pills identical in appearance to varenicline

* Placebo pills (identical to varenicline)
* NicodermCQ (Nicotine Patches): Administered according to package insert directions
* Behavioral Counseling Sessions: Participants will attend one-on-one behavioral counseling sessions with a trained therapist at each of 4 study visits (pre-quit, quit date, week 2, and week 12). Behavioral sessions will involve teaching behavioral skills to assist with smoking cessation, preventing relapse, and coping with physical or emotional changes associated with cravings.
Interventions: intervention 1: Chantix intervention 2: Behavioral Counseling Sessions intervention 3: NicodermCQ intervention 4: Placebo
Intervention descriptions: intervention 1: Chantix given alongside standard smoking cessation treatment, and administered per manufacturer's instructions \[0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then one 1.0 mg tablet twice per day\] intervention 2: One-to-one behavioral counseling sessions with a trained therapist intervention 3: Nicotine patches provided over 12 week participation intervention 4: Identical in appearance to varenicline \[0.5 mg once per day for Days 1 to 3, 0.5 mg twice per day for Days 4 to 7, then one 1.0 mg tablet twice per day\]

Protocol documents:
Prot_SAP_000.pdf: 
NCT02859142 
 
Study protocol w/ SAP 
 
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NCT#: NCT02859142  
Unique Protocol ID: 15-1615 
Official Title: Varenicline Augmentation of Patch Outcomes in Heavy Drinkers' Smoking Cessation 
 
Document date: 8/13/2021 
 
 
 
Study Protocol with SAP 
 
Design overview 
The study was a randomized, double-blinded, placebo-controlled treatment trial evaluating 
varenicline combined with nicotine patch and counseling compared with placebo plus nicotine patch 
and counseling on smoking cessation and drinking behavior in HDS. The study was fully approved by the 
University of Chicago Institutional Review Board. 
Participants were enrolled between February 2018-February 2020. The majority of study visits 
(88%) took place at the Clinical Addictions Research Laboratory – East facility at the University of 
Chicago and 12% of visits were conducted at the Respiratory Health Association of Chicago. Participants 
were recruited via advertisements on social media, public transit and community outreach to local 
organizations. Candidates completed a brief phone interview and those deemed eligible were invited to 
an in-person screening visit. Eligibility criteria included age 18-85 years, seeking treatment for smoking 
cessation, smoking >5 and < 30 cigarettes daily, English fluency, ≥8th grade education, stable residence, 
and no history of adverse reactions to varenicline or nicotine patch. Candidates were also required to 
meet hazardous drinking levels consistent with the National Institute on Alcohol and Alcoholism (NIAAA) 
guidelines [>14/7 drinks weekly for men/women and ≥1 heavy drinking days (>5/4 drinks per occasion 
for men/women) per month for the past year] (National Institute on Alcohol Abuse and Alcoholism 
(NIAAA), 2005).  Desire to change drinking was not a requirement for enrollment. Individuals with any 
major medical or psychiatric contraindications, including uncontrolled hypertension, history of seizures, 
liver enzymes outside of the normal range, current suicidal ideation, and severe alcohol withdrawal 


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symptoms when stopping drinking, determined by the study physician to be at significant risk for 
adverse interactions with study medications or measures were deemed ineligible and were not 
included. Also for women, current pregnancy or breastfeeding, plans to become pregnant in the next 
three months, or not using effective birth control were reasons for non-inclusion.   
At the screening visit, candidates completed surveys on demographics, medical history, 
smoking, mood, and substance use history. They also completed a Fagerström Test for Cigarette 
Dependence (Fagerström, 2012), the Structured Clinical Interview for DSM-IV, nonpatient version (First 
et al., 1995), the Columbia Suicide Severity Rating Scale (CSSRS; Posner et al., 2011), the Alcohol Use 
Disorder Identification Test (AUDIT; Babor et al., 2001), and a Timeline Follow-back Interview of past 
month (28-day) daily cigarette and alcohol use. Upon arrival, candidates were required to have a breath 
alcohol concentration of 0.00 g/dl, a score < 10 on the Clinical Institute Withdrawal Assessment for 
Alcohol (CIWA-Ar; Sullivan et al., 1989), and test negative for all drugs of abuse (except cannabis). 
Individuals deemed eligible at in-person screening were accepted into the study and worked with the 
research assistant to schedule their 4 study visits with their target smoking quit date on the second 
study visit. 
Randomization and interventions 
Randomization to varenicline or placebo was stratified by sex and smoking level (light, <10 
cigs/day vs heavy, ≥10 cigs/day). Pfizer, Inc. supplied both the varenicline and matching placebo pills. 
Participants and research staff were blind to treatment assignments throughout the study.  Study 
participation began with the randomization visit occurring one week prior to the scheduled quit date.  
Subsequent study visits occurred on quit day (week 0), week 2, and week 12 (end of treatment).  The 
follow-up assessment took place at week 26.  Medication was started one week before the target quit 
date. The titration for varenicline followed the standard dosing regimen: 0.5 mg once daily for 3 days, 
0.5 twice daily for 4 days, and 1 mg twice daily for the remainder of the 12 weeks of treatment. After 


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Week 12, participants were given the option for a down-titration dosing schedule of 0.5 mg twice daily 
for 4 days and then 0.5 mg once daily for 3 days. Participants assigned to placebo received identical-
appearing tablets with the same dosing instructions. Dose reductions were allowed and participants 
who discontinued medication could continue attending counseling and research sessions and continue 
receiving nicotine patches. All participants initiated nicotine patch on quit day and continued daily at 
dosing levels recommended by the manufacturer for 10 weeks (i.e. lighter smokers: 14 mg daily for first 
6 weeks then 7 mg daily for 4 weeks; heavier smokers: 21 mg daily for the first 6 weeks, then 14 mg 
daily for 2 weeks, and then 7 mg daily for 2 weeks). Medication and patch compliance was monitored 
through a combination of pill and patch counts returned at each study visit and self-reported daily log 
entries of pill and patch use that participants completed at home and returned to each study visit. 
At the first two study visits, participants met with a trained smoking cessation facilitator and 
received semistructured, individual counseling sessions adapted from Courage to Quit, an evidence-
based smoking cessation intervention developed by the principal investigator (A.K.; Asvat et al., 2014). 
At the randomization visit, the 30-45 minute counseling session supported medication adherence and 
discussed preparing for quit day, which was set to occur on the same day as completing the varenicline 
up-titration. At the quit day visit, the 15-20 minute counseling session addressed techniques for coping 
with smoking urges and nicotine withdrawal symptoms.  
Participants received $60 in compensation at the end of treatment and $40 for the follow-up at 
week 26. Individuals who indicated past-week smoking abstinence at follow-up attended an in person 
visit for biochemical verification and were eligible for an additional $20-$50 in compensation from a 
random drawing. 
Assessments 
 
At each of the four study visits, participants completed breath tests for CO and alcohol, vital sign 
readings, and body weight measurements, as well as the following interviews: CIWA-Ar, CSSRS, and 


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Timeline Follow-back for daily cigarette and alcohol use since the prior visit. Participants also returned 
any unused pills and patches and a completed calendar log of daily pill and patch use. The Brief 
Questionnaire of Smoking Urges (Cox et al., 2001) and Minnesota Nicotine Withdrawal Scale-Revised 
(Hughes, 2017) were also administered at each visit. In addition, participants completed a 16-item 
assessment of varenicline and nicotine patch adverse effects during the week prior to their visit and, if 
present, rated their experiences as mild, moderate, or severe. 
Statistical analysis 
 
Demographic and baseline characteristics were compared between groups using Student’s t 
test, chi-square test, or Fisher’s exact test of independence as appropriate. The primary outcome was 
continuous cigarette abstinence during weeks 9-12 of treatment as confirmed by a breath CO reading of 
≤ 10 ppm at the week 12 visit. A logistic regression model adjusting for baseline cigarettes per smoking 
day analyzed this outcome, as well as the 7-day point prevalence of smoking abstinence at week 26.  
Self-reported continuous smoking abstinence throughout 12 weeks of active treatment were compared 
by a Cox Hazard model adjusting baseline cigarettes per smoking day. For these analyses, all randomized 
participants (i.e. those who received at least one medication dose as the first dose was taken under 
observation during the first study visit) were included, with drop-outs conservatively classified as 
relapsed to smoking. Due to local mandatory quarantine restrictions imposed as a result of the COVID-
19 pandemic, thirteen participants (varenicline, n=9; placebo, n=4) were unable to complete their week 
12 visit in-person and thus, their smoking statuses could not be biochemically verified. Of these 
participants, nine (varenicline, n=7; placebo, n=2) self-reported smoking abstinence during weeks 9-12 
and were treated as abstinent in analyses of smoking outcomes. 
For the drinking outcomes among those who did not drop out of the study, Generalized 
Estimating Equation models were used to compare changes from baseline in drinks per week and 
weekly heavy drinking days between medication condition during the 12-week treatment period. For 


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baseline drinks per week, 3 subjects were identified as outliers (>3 SD above the mean) and as a result, 
their data were normalized to 3 SD of the sample mean prior to analysis. At week 26, Changes from 
baseline drinks per week and weekly heavy drinking days were compared by t-tests. 
Sample size calculations were based on data obtained from several studies examining 
varenicline on smoking and drinking outcomes and our past community-based smoking cessation 
intervention study (King et al., 2012).  Varenicline’s effect was obtained from prior research on quit rates 
(44%; Burke et al., 2016; Jorenby et al., 2006) and as the placebo group was receiving an active 
treatment, we expected slightly higher quit rates compared to those obtained in earlier varenicline 
clinical trials (18%). Therefore, we deemed 61 subjects per group to be sufficient to detect a significant 
difference between groups with 80% power and at a 0.05 level of significance.  
 
References: 
Asvat Y, Cao D, Africk JJ, Matthews A, King A (2014) Feasibility and effectiveness of a community-based 
smoking cessation intervention in a racially diverse, urban smoker cohort. Am J Public Health 104. 
Babor TF, De La Fuente JR, Saunders JB, Grant M (2001) Substance Abuse Disorders Identification Test: 
Guidelines for use in Primary Health Care. Geneva, Switzerland. 
Burke M V., Hays JT, Ebbert JO (2016) Varenicline for smoking cessation: A narrative review of efficacy, 
adverse effects, use in at-risk populations, and adherence. Patient Prefer Adherence 10:435–441. 
Cox LS, Tiffany ST, Christen AG (2001) Evaluation of the brief questionnaire of smoking urges (QSU-brief) 
in laboratory and clinical settings. Nicotine Tob Res 3:7–16. 
Fagerstrom K (2012) Determinants of Tobacco Use and Renaming the FTND to the Fagerstrom Test for 
Cigarette Dependence. Nicotine Tob Res 14:75–78. 
First M, Spitzer R, Gibbon M, Williams J (1995) Structured Clinical Interview for DSM-IV Axis 1 Disorders, 
Research Version, Patient Edition (SCID-I/P). New York, NY, Biometrics Research, New York State 
Psychiatric Institute. 
Hughes JR (2017) Background on the Minnesota Tobacco Withdrawal Scale - Revised (MTWS-R). 
Available at: http://contentmanager.med.uvm.edu/docs/background/behavior-and-health-
documents/background.pdf?sfvrsn=2 Accessed April 7, 2021. 
Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR, 
Varenicline Phase 3 Study Group (2006) Efficacy of Varenicline, an α4β2 Nicotinic Acetylcholine 
Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking 
Cessation&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt; JAMA 296:56. 
King AC, Cao D, O’Malley SS, Kranzler HR, Cai X, Dewit H, Matthews AK, Stachoviak RJ (2012) Effects of 
naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and 
women. J Clin Psychopharmacol 32:630–636. 
National Institute on Alcohol Abuse and Alcoholism (NIAAA) (2005) Helping patients who drink too 
much: a clinician’s guide, National Institute on Alcohol and Alcoholism. Bethesda, MD. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova K V., Oquendo MA, Currier GW, Melvin GA, Greenhill 


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L, Shen S, Mann JJ (2011) The Columbia-suicide severity rating scale: Initial validity and internal 
consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 
168:1266–1277. 
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM (1989) Assessment of alcohol withdrawal: 
the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 
84:1353–7.