Tobacco Dependence
Conditions
Keywords
Varenicline, Nicotine Patch, Quit Smoking, Tobacco, Cigarettes
Brief summary
This research will determine whether two highly promising modifications to varenicline treatment (i.e. use of a nicotine patch adjuvant and extended 24-week duration) produce superior smoking outcomes when they are either used together or alone. Despite their promise, the proposed modifications have never been experimentally evaluated relative to standard varenicline pharmacotherapy. Thus, this innovative research will produce novel evidence regarding how best to help smokers quit, and thereby address the leading cause of preventable mortality and morbidity related to cardiovascular and pulmonary diseases.
Detailed description
Building on our recent NHLBI-funded publication in JAMA (see references below) that described the modest effectiveness of varenicline pharmacotherapy, this study will use a 2 X 2 factorial design to evaluate two different medication use strategies on their ability to markedly enhance varenicline effectiveness in a large cohort of current smokers. Smokers (N=1000) will be randomly assigned to one of two levels for each of two factors: 1) an Adjuvant factor (varenicline + placebo patch versus varenicline + nicotine patch), and 2) a Duration factor (12 versus 24 weeks of active medication). Thus, this factorial design yields a standard varenicline treatment (12 weeks of active varenicline and 12 weeks of placebo varenicline + 24 weeks of placebo patch), and 3 enhanced treatments: 1) 12 weeks of active varenicline and 12 weeks of placebo varenicline + 24 weeks of active patch, 2) 24-weeks of active varenicline + 24 weeks of placebo patch, and 3) 24 weeks of active varenicline + 24 weeks of active patch. Both treatment modifications, longer duration therapy and use of a nicotine replacement therapy (NRT) adjuvant, have produced some quite promising effects. However, in both cases these modifications have been little researched, their effects are not consistently positive, and they have not been implemented in a potentially optimal manner. We will implement each modification in an innovative manner designed to enhance its effectiveness. In addition, all participants will be given counseling that supports adherent medication use and that is readily translatable to healthcare settings. The scientific rigor of this work will be enhanced by the use of placebo medication, a large sample, and a factorial design. The latter will allow us to test both the main and interaction effects of the experimental factors. We will also be able to compare each enhanced treatment with standard 12-week varenicline-only therapy to determine whether any of these medication use strategies significantly enhances treatment effectiveness.
Interventions
DRUGVarenicline
0.5mg and 1.0 mg pills used. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.)
DRUGNicotine patch
14 mg and 7 mg nicotine patches used. See arms for specific durations.
OTHERPlacebo Patch
Placebo patches matched in appearance to the Active 14 mg and 7 mg nicotine patches used in the Nicotine patch intervention. See arms for specific durations.
OTHERPlacebo Pill
Placebo pills matched in appearance to the Active Varenicline pills in the Varenicline intervention. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.)
Sponsors
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Active and placebo medications are identical in appearance. Medication labeling and the dispensing protocol are designed to prevent participants and care providers from knowing if the medication is active or placebo.
Intervention model description
Double Blinded Placebo Controlled Factorial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Participants must: plan to stay in the area for the next 12 months, ability to read and write in English, smoke on average ≥5 cigarettes per day over the last 6 months, be ≥18 years old, desire to quit smoking but not be engaged currently in cessation treatment, report no use of pipe tobacco, cigars, snuff, e-cigarettes or chew in the last 30 days, have reliable phone access, willing and able to use both nicotine patch and varenicline, access to transportation to come to our clinic and, if female, not be pregnant and be using an acceptable birth control method/ method to prevent pregnancy. Smoking will be biochemically confirmed via a carbon monoxide (CO) breath test at the orientation session visit. Potential participants must have a CO test result of ≥5ppm for eligibility to participate.
Exclusion criteria
Current treatment for schizophrenia or a psychotic disorder; suicidal ideation in the past 12 months; history of suicidal attempts within the last 10 years; on dialysis or being told you have severe kidney disease; hospitalization for a stroke, heart attack, congestive heart failure or uncontrolled diabetes mellitus within the past year; history of seizure within the last year; currently taking Wellbutrin, Zyban, or Buproprion (Contrave is a weight-loss drug that has Wellbutrin in it) for reasons other than to quit smoking or taking to help quit smoking and not willing to stop for duration of the study; currently using any form of nicotine replacement (e.g., nicotine patch, nicotine gum, nicotine lozenge) or using Chantix or varenicline and not willing to stop for duration of the study; had a reaction to the nicotine patch that prevented them from continuing to use it; or currently participating in another smoking cessation study. Pregnancy: Even though we screen out participants who are pregnant, plan to become pregnant, nursing, or are unwilling to take steps to avoid pregnancy, there is a chance that a participant eligible at consent could become pregnant later. She would then be considered part of a vulnerable group. Given the longitudinal nature of the research, a participant who becomes pregnant after enrolling will be given the choice of whether to 1) continue in the study (for counseling and other assessments) and agree to immediately stop taking study meds for the remaining duration of the study and return any unused medications, OR 2) withdraw. No further medications will be given to this study participant while in the study. Incarcerated Individuals: Incarcerated individuals will not be enrolled in this study. However, given the longitudinal nature of the research, participants could be incarcerated for periods during their participation. If study staff learn that a participant is incarcerated at a time point before or at their Week 8 phone call, the participant will be withdrawn from the study. If study staff learn that a participant is incarcerated subsequent to Week 8, the participant will not be withdrawn unless that incarceration will take them beyond the study period. In that case, staff will not contact the participant while incarcerated and will not provide any treatment (counseling or medication) nor conduct any assessments during the period of incarceration. Services and assessments will be re-initiated if the participant is released at a later study time point.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 52-Week Point-Prevalence Abstinence | Assessed 52 weeks after quit date | Biochemically-confirmed self-reported total abstinence from any cigarette use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 23-Week Point-Prevalence Abstinence | Assessed 23 weeks after quit date | Biochemically confirmed self-reported total abstinence from any cigarette use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm. |
| 52-Week Prolonged Abstinence | Assessed 52 weeks after quit date | Biochemically confirmed self-reported total abstinence from any cigarette use (even a single puff) from week 2 post-quit through week 52 post-quit, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm. |
| 23-Week Prolonged Abstinence | Assessed 23 weeks after quit date | Biochemically confirmed self-reported total abstinence from any cigarette use (even a single puff) from week 2 post-quit through week 23 post-quit, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred via community outreach (e.g., social networking sites, radio, TV, newspaper). Interested respondents were called and screened for initial eligibility; those eligible attended a group orientation session that entailed: final eligibility assessment, written informed consent, baseline assessments, biochemical confirmation of smoking status, and randomization. Study visits were in Madison and Milwaukee, WI. First participant enrolled on 11/11/17; study completed on 7/9/20.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline + Patch Standard Duration Standard Condition Varenicline: 0.5 mg pill QD on Days -7 to -5; 0.5 mg pill BID Days -4 to -1; 1 mg pill BID Days 1 to Week 11; Placebo Pill weeks 12-23 BID
Standard Condition Nicotine Patches:
Patches (Nicotine): 14 mg Patches for 2 weeks prequit and then 10 weeks post-quit, then 7 mg patches for Weeks 11 and 12; Placebo patches weeks 13-24
Varenicline: 0.5mg and 1.0 mg pills used. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.)
Nicotine patch: 14 mg and 7 mg nicotine patches used. See arms for specific durations.
Placebo Patch: Placebo patches matched in appearance to the Active 14 mg and 7 mg nicotine patches used in the Nicotine patch intervention. See arms for specific durations.
Placebo Pill: Placebo pills matched in appearance to the Active Varenicline pills in the Varenicline intervention. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.) | 314 |
| Varenicline Only Standard Duration Standard Condition Varenicline: 0.5 mg pill QD on Days -7 to -5; 0.5 mg pill BID Days -4 to -1; 1 mg pill BID Days 1 to Week 11; Placebo Pill weeks 12-23 BID
Standard Condition Placebo Patches:
Placebo patches for 2 weeks prequit and for weeks 1-24 post-quit
Varenicline: 0.5mg and 1.0 mg pills used. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.)
Placebo Patch: Placebo patches matched in appearance to the Active 14 mg and 7 mg nicotine patches used in the Nicotine patch intervention. See arms for specific durations.
Placebo Pill: Placebo pills matched in appearance to the Active Varenicline pills in the Varenicline intervention. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.) | 315 |
| Varenicline + Patch Extended Duration Extended Condition Varenicline: 0.5 mg pill QD on Days -7 to -5, 0.5 mg pill BID Days -4 to -1, and 1 mg pill BID Days 1 to Week 22
Extended Condition Nicotine Patches:
14 mg Patches for 2 weeks prequit and then weeks 1-22 post-quit, then 7 mg patches for Weeks 23 and 24 post-quit.
Varenicline: 0.5mg and 1.0 mg pills used. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.)
Nicotine patch: 14 mg and 7 mg nicotine patches used. See arms for specific durations. | 311 |
| Varenicline Only Extended Duration Extended Condition Varenicline: 0.5 mg pill QD on Days -7 to -5, 0.5 mg pill BID Days -4 to -1, and 1 mg pill BID Days 1 to Week 22
Extended Condition Placebo Patches:
Placebo patches for 2 weeks prequit and for weeks 1-24 post-quit
Varenicline: 0.5mg and 1.0 mg pills used. See arms for specific durations. (Active and placebo varenicline pills provided at no cost through an independent research agreement with Pfizer.)
Placebo Patch: Placebo patches matched in appearance to the Active 14 mg and 7 mg nicotine patches used in the Nicotine patch intervention. See arms for specific durations. | 311 |
| Total | 1,251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 77 | 79 | 79 | 49 |
| Overall Study | Withdrawal by Subject | 28 | 34 | 34 | 21 |
Baseline characteristics
| Characteristic | Varenicline + Patch Standard Duration | Total | Varenicline Only Extended Duration | Varenicline + Patch Extended Duration | Varenicline Only Standard Duration |
|---|---|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 12.4 | 49.1 years STANDARD_DEVIATION 11.9 | 49.9 years STANDARD_DEVIATION 11.5 | 48.9 years STANDARD_DEVIATION 12.3 | 48.6 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 41 Participants | 5 Participants | 12 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 285 Participants | 1164 Participants | 297 Participants | 285 Participants | 297 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 46 Participants | 9 Participants | 14 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 14 Participants | 2 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 8 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 71 Participants | 287 Participants | 78 Participants | 68 Participants | 70 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 27 Participants | 7 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 45 Participants | 7 Participants | 14 Participants | 12 Participants |
| Race (NIH/OMB) White | 221 Participants | 867 Participants | 214 Participants | 213 Participants | 219 Participants |
| Region of Enrollment United States | 314 participants | 1251 participants | 311 participants | 311 participants | 315 participants |
| Sex: Female, Male Female | 171 Participants | 675 Participants | 167 Participants | 166 Participants | 171 Participants |
| Sex: Female, Male Male | 143 Participants | 576 Participants | 144 Participants | 145 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 314 | 0 / 315 | 0 / 311 | 0 / 311 |
| other Total, other adverse events | 194 / 305 | 164 / 300 | 159 / 295 | 160 / 307 |
| serious Total, serious adverse events | 0 / 314 | 1 / 315 | 0 / 311 | 1 / 311 |
Outcome results
Primary
52-Week Point-Prevalence Abstinence
Biochemically-confirmed self-reported total abstinence from any cigarette use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm.
Time frame: Assessed 52 weeks after quit date
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline + Patch Standard Duration | 52-Week Point-Prevalence Abstinence | 74 Participants |
| Varenicline Only Standard Duration | 52-Week Point-Prevalence Abstinence | 79 Participants |
| Varenicline + Patch Extended Duration | 52-Week Point-Prevalence Abstinence | 78 Participants |
| Varenicline Only Extended Duration | 52-Week Point-Prevalence Abstinence | 76 Participants |
p-value: 0.6695% CI: [0.6, 1.3]Regression, Logistic
p-value: 0.8595% CI: [0.7, 1.4]Regression, Logistic
p-value: 195% CI: [0.7, 1.4]Regression, Logistic
Secondary
23-Week Point-Prevalence Abstinence
Biochemically confirmed self-reported total abstinence from any cigarette use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm.
Time frame: Assessed 23 weeks after quit date
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline + Patch Standard Duration | 23-Week Point-Prevalence Abstinence | 74 Participants |
| Varenicline Only Standard Duration | 23-Week Point-Prevalence Abstinence | 66 Participants |
| Varenicline + Patch Extended Duration | 23-Week Point-Prevalence Abstinence | 82 Participants |
| Varenicline Only Extended Duration | 23-Week Point-Prevalence Abstinence | 70 Participants |
p-value: 0.4495% CI: [0.8, 1.7]Regression, Logistic
p-value: 0.6195% CI: [0.8, 1.6]Regression, Logistic
p-value: 0.1295% CI: [0.9, 2]Regression, Logistic
Secondary
23-Week Prolonged Abstinence
Biochemically confirmed self-reported total abstinence from any cigarette use (even a single puff) from week 2 post-quit through week 23 post-quit, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm.
Time frame: Assessed 23 weeks after quit date
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline + Patch Standard Duration | 23-Week Prolonged Abstinence | 66 Participants |
| Varenicline Only Standard Duration | 23-Week Prolonged Abstinence | 72 Participants |
| Varenicline + Patch Extended Duration | 23-Week Prolonged Abstinence | 73 Participants |
| Varenicline Only Extended Duration | 23-Week Prolonged Abstinence | 65 Participants |
p-value: 0.6595% CI: [0.6, 1.3]Regression, Logistic
p-value: 0.695% CI: [0.6, 1.3]Regression, Logistic
p-value: 0.8695% CI: [0.7, 1.5]Regression, Logistic
Secondary
52-Week Prolonged Abstinence
Biochemically confirmed self-reported total abstinence from any cigarette use (even a single puff) from week 2 post-quit through week 52 post-quit, confirmed with an exhaled carbon monoxide reading of less than or equal to 5 ppm.
Time frame: Assessed 52 weeks after quit date
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline + Patch Standard Duration | 52-Week Prolonged Abstinence | 47 Participants |
| Varenicline Only Standard Duration | 52-Week Prolonged Abstinence | 55 Participants |
| Varenicline + Patch Extended Duration | 52-Week Prolonged Abstinence | 57 Participants |
| Varenicline Only Extended Duration | 52-Week Prolonged Abstinence | 46 Participants |
p-value: 0.4395% CI: [0.5, 1.3]Regression, Logistic
p-value: 0.3795% CI: [0.5, 1.3]Regression, Logistic
p-value: 0.8195% CI: [0.7, 1.6]Regression, Logistic