Nicotine Dependence, Smoking, Smoking Cessation
Conditions
Keywords
Smoking Cessation, Smoking, Nicotine
Brief summary
The overall purpose of this research is two-fold. First, the two smoking cessation medication treatments with the strongest evidence of effectiveness have never been directly compared. This research will determine how these two treatments compare in effectiveness in a head-to-head trial, and which types of smokers benefit most from each. Second, much of the data on smoking and health come from studies from many years ago. Today's smokers differ from earlier smokers in many ways that could influence the impact of smoking on health (e.g., weight, sex, diet, socio-economic status); the proposed work will determine how smoking cessation affects cardiovascular and pulmonary health in today's smokers.
Detailed description
The proposed study will recruit and treat a large sample of contemporary smokers and former smokers at an age of increasing health risk, to achieve the following over-arching aims that are important to the NHLBI mission: * Specific Aim 1: Produce important new data on how to treat smoking optimally by conducting an open label comparative effectiveness trial (CET) that for the first time directly contrasts the two smoking cessation pharmacotherapies with the strongest extant evidence of efficacy: combination NRT and varenicline. * Specific Aim 2: Determine the impact of smoking cessation on biomarkers and health risk factors, especially those relevant to CVD, in today's smokers, which will elucidate the mechanisms via which cessation benefits health. * Specific Aim 3: Identify which individuals are at greatest risk for exacerbation of biomarkers or risk factor status due to continued smoking, and who will benefit most from cessation. This will help identify individuals who are most in need of cessation intervention. While all smokers need to quit, this evidence could ultimately be used to help focus treatment and motivate smokers and clinicians to intervene more intensively with patients at greatest risk. Two secondary aims are to use the results of Primary Aim 1 to develop a treatment assignment algorithm for the optimal treatment of today's smokers and to use the results from Primary Aim 2 to determine the relation of health biomarkers to clinically meaningful disease outcomes such as CVD events. We will re-recruit as many smoking and non smoking participants from our past longitudinal cohort study(Wisconsin Smokers' Health study; NCT01122238) in 2004. We will then recruit additional smokers to participate in the comparative effectiveness trial and join the longitudinal cohort.. All participants who enroll will complete questionnaires about their demographics, smoking history, withdrawal symptoms, affect, alcohol use, stressors, medication usage and diet. They will also complete a structured clinical interview to assess mental health. They will provide blood samples for testing of various markers of cardiovascular disease and risk as well as for genetics testing. They will all have carotid ultrasounds, pulmonary function tests, arterial tonometry assessments, and 12-lead ECGs. Participants in Madison will also have a treadmill stress test. Participants will wear a pedometer for 1 week and record the daily number of steps. Participants will provide permission for staff to review their medical charts to assess smoking-relevant diagnoses and treatment. These assessments will occur at baseline and again 3 years later. A smaller subset of these assessments will also be conducted 1 year after enrollment. Participants will also complete brief phone assessments at 6-month intervals up to the 3-year visit. Interested and eligible smoking participants from the original cohort study and all newly recruited participants will enroll in a new smoking cessation intervention study. Participants in the cessation treatment study will be randomly assigned to receive the nicotine patch, nicotine patch + nicotine lozenge or varenicline. If the participant from the original cohort study is not eligible to use all study medications but is otherwise eligible for cessation treatment, s/he will be assigned to a non-randomized treatment arm and will receive nicotine patch (if appropriate). All cessation participants will receive 6 individual counseling sessions.
Interventions
DRUGNicotine Patch
Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.
DRUGVarenicline
Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.
DRUGNicotine lozenge
Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
We are only recruiting by invitation only (to members of our past cohort). We will open up enrollment to the public in the Madison, WI and Milwaukee WI areas at the end of 2012. Inclusion Criteria: a. To be eligible for the Comparative effectiveness trial, participants must: * smoke 5 or more cigarettes per day, * desire to quit smoking but not be currently engaged in cessation treatment, * be medically eligible to use either combination NRT or varenicline, * have reliable phone access, * if female, must not be pregnant and must be willing to use an acceptable birth control method.
Exclusion criteria
1. There are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks | Assessed 26 weeks after the target quit day. | Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of \<10 ppm.. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days to Relapse | Assessed from the target quit day through 26 weeks. | The number of days to relapse is defined as the number of days from the target quit day until the first of seven consecutive days of smoking. |
| Number of Participants With Initial Cessation in the First 7 Days Post-quit | Assessed for the first seven days after the target quit date. | Defined as at least 1 day of abstinence during the first 7 days after the target quit day. |
| The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT). | Assessed at Baseline and Year 3 | Change in carotid intima-media thickness (CIMT) from Baseline to Year 3 as a function of smoking status (abstinent versus smoking) at Year 3. Change is calculated as Baseline CIMT score minus Year 3 CIMT score. CIMT score is thickness of the carotid intima-media in millimeters (mm). Lower CIMT values indicate a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Effectiveness of Nicotine Patch Only Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects. | 241 |
| Effectiveness of Combination NRT Nicotine lozenge: Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects.
Nicotine Patch: Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects. | 421 |
| Effectiveness of Varenicline [Chantix] Varenicline: Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised. | 424 |
| Total | 1,086 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 15 | 13 | 35 |
Baseline characteristics
| Characteristic | Effectiveness of Nicotine Patch Only | Total | Effectiveness of Varenicline [Chantix] | Effectiveness of Combination NRT |
|---|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 10.9 | 48.1 years STANDARD_DEVIATION 11.6 | 48.5 years STANDARD_DEVIATION 11.8 | 47.1 years STANDARD_DEVIATION 11.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 72 Participants | 309 Participants | 120 Participants | 117 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 22 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 18 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) White | 158 Participants | 728 Participants | 283 Participants | 287 Participants |
| Region of Enrollment United States | 241 participants | 1086 participants | 424 participants | 421 participants |
| Sex: Female, Male Female | 125 Participants | 566 Participants | 222 Participants | 219 Participants |
| Sex: Female, Male Male | 116 Participants | 520 Participants | 202 Participants | 202 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 241 | 6 / 421 | 5 / 424 |
| other Total, other adverse events | 164 / 241 | 281 / 421 | 353 / 424 |
| serious Total, serious adverse events | 0 / 241 | 0 / 421 | 1 / 424 |
Outcome results
Primary
Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks
Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day, confirmed with an exhaled carbon monoxide reading of \<10 ppm..
Time frame: Assessed 26 weeks after the target quit day.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Effectiveness of Nicotine Patch Only | Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks | 63 Participants |
| Effectiveness of Combination NRT | Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks | 124 Participants |
| Effectiveness of Varenicline [Chantix] | Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks | 108 Participants |
Comparison: Combination NRT will be compared statististically versus Nicotine patch only (the reference or control group).p-value: 0.362395% CI: [0.8, 1.7]Regression, Logistic
Comparison: Varenicline will be compared statististically versus Nicotine patch only (the reference or control group).p-value: 0.194795% CI: [0.6, 1.2]Regression, Logistic
Secondary
Number of Days to Relapse
The number of days to relapse is defined as the number of days from the target quit day until the first of seven consecutive days of smoking.
Time frame: Assessed from the target quit day through 26 weeks.
Population: Participants who did not relapse were censored in the survival analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Effectiveness of Nicotine Patch Only | Number of Days to Relapse | 29.3 Days | Standard Deviation 42.4 |
| Effectiveness of Combination NRT | Number of Days to Relapse | 37.4 Days | Standard Deviation 46.5 |
| Effectiveness of Varenicline [Chantix] | Number of Days to Relapse | 31.7 Days | Standard Deviation 46.7 |
p-value: 0.361395% CI: [0.756, 1.107]Regression, Cox
p-value: 0.550395% CI: [0.779, 1.142]Regression, Cox
Secondary
Number of Participants With Initial Cessation in the First 7 Days Post-quit
Defined as at least 1 day of abstinence during the first 7 days after the target quit day.
Time frame: Assessed for the first seven days after the target quit date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Effectiveness of Nicotine Patch Only | Number of Participants With Initial Cessation in the First 7 Days Post-quit | 176 Participants |
| Effectiveness of Combination NRT | Number of Participants With Initial Cessation in the First 7 Days Post-quit | 339 Participants |
| Effectiveness of Varenicline [Chantix] | Number of Participants With Initial Cessation in the First 7 Days Post-quit | 289 Participants |
p-value: 0.0395% CI: [1.1, 2.2]Regression, Logistic
p-value: 0.1995% CI: [0.6, 1.1]Regression, Logistic
Secondary
The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT).
Change in carotid intima-media thickness (CIMT) from Baseline to Year 3 as a function of smoking status (abstinent versus smoking) at Year 3. Change is calculated as Baseline CIMT score minus Year 3 CIMT score. CIMT score is thickness of the carotid intima-media in millimeters (mm). Lower CIMT values indicate a better outcome.
Time frame: Assessed at Baseline and Year 3
Population: Includes only participants who completed both Baseline and Year 3 CIMT measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Effectiveness of Nicotine Patch Only | The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT). | -0.0682 millimeters (mm) | Standard Deviation 0.0689 |
| Effectiveness of Combination NRT | The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT). | -0.0620 millimeters (mm) | Standard Deviation 0.0755 |
p-value: 0.3282t-test, 2 sided