Pulmonary Disease, Chronic Obstructive, Smoking, Tobacco Use Disorder
Conditions
Keywords
smoking cessation, tobacco use cessation products, nicotine
Brief summary
Long-term NRT has not been studied in patients with COPD, and smokers in the United States with COPD are still asked to choose between immediate quitting or continued smoking. The purpose of this study is to see if guided maintenance therapy (GMT), using long-term NRT, might prove to be a reasonable alternative to the standard approach of asking patients to quit immediately. The investigators believe that GMT with long-term NRT will reduce overall exposure to cigarette smoke, reduce harm related to smoking, and ultimately lead to greater quit rates. In this study, 398 smokers with COPD will be randomly assigned to either receive: 1) traditional smoking cessation (SC) or 2) long-term, guided maintenance therapy with NRT (GMT). The SC intervention will be based on a standard approach to smoking cessation, including smoking cessation counseling supplemented with combination NRT (a nicotine patch plus the patient's choice of gum or lozenge) if they are willing to make a quit attempt. The GMT intervention will consist of counseling, focused on medication adherence and smoking reduction, plus 52 weeks of combination NRT. After 3, 6 and 12 months of treatment, we will compare the two treatments based on their effects on smoking cessation, number of cigarettes smoked, exposure to carbon monoxide and smoking-related carcinogens, COPD symptoms, breathing function, and smoking-related hospitalizations or death. The investigators will also analyze the data in such a way that will be able to identify which patients are most likely to benefit from treatment. This analysis will allow patients to estimate their chances of success based on their own personal characteristics and which treatment they choose. The investigators study addresses research priorities identified in recent smoking cessation guidelines and builds upon the input of our Patient Advisory Panel and our Stakeholder Advisory Committee. This study reflects the interests expressed by smokers in prior surveys and addresses the limited reach and effectiveness of traditional approaches to smoking cessation. If our GMT approach is effective, our study could change the recommendations provided in clinical practice guidelines and change the way that insurance companies pay for smoking cessation treatment. GMT could provide an alternative for millions of smokers with COPD who are not currently benefiting from traditional approaches to smoking cessation
Detailed description
BACKGROUND Smokers with chronic obstructive pulmonary disease (COPD) recognize the dangers of continued smoking and would like to quit, but for most of them the idea of going 'cold turkey' is too intimidating. Many of these smokers would like to cut back on the amount that they smoke as part of a longer term path to quitting. Long-term nicotine replacement therapy (NRT) might allow them to do this. Long-term NRT is safe; it can reduce the rewarding effects of cigarettes, reduce the amount that people smoke, and increase quit rates. Long-term NRT has not, however, been studied in patients with COPD, and smokers in the United States with COPD are still asked to choose between immediate quitting or continued smoking. The purpose of this study is to evaluate the relative benefits of a third option: guided maintenance therapy with long-term NRT. We believe that long-term NRT could reduce overall exposure to cigarette smoke, reduce harm related to smoking, and ultimately lead to greater quit rates. OBJECTIVES 1. Compare the benefits of traditional smoking cessation (SC) versus guided maintenance therapy (GMT) with NRT for smokers with COPD. 2. Estimate rates of smoking cessation and other patient-desired outcomes based on patient-specific characteristics and treatment choice (SC or GMT). METHODS In this study, we will randomize 398 smokers with COPD to one of two treatment arms: 1) traditional smoking cessation (SC) or 2) long-term, guided maintenance therapy with NRT (GMT). Participants in the SC arm will receive a standard approach to smoking cessation, including smoking cessation counseling supplemented with combination NRT (nicotine patch plus choice of gum or lozenge) if they are willing to make a quit attempt. Participants in the GMT arm will receive counseling focused on medication adherence and smoking reduction plus 52 weeks of combined NRT. Outcomes will be measured at 3, 6 and 12 months post-randomization and will assess rates of smoking cessation, number of cigarettes smoked, exposure to carbon monoxide and smoking-related carcinogens, and clinical outcomes including respiratory symptoms, respiratory function, and smoking-related hospitalizations or death. In addition to directly comparing outcomes in the two treatment arms, our novel classification and regression tree analysis will allow us to identify subgroups of patients most likely to benefit from treatment and will allow patients to estimate their projected outcomes given their personal history and their choice of therapy. PATIENT OUTCOMES (PROJECTED) This study will show how long-term NRT compares to a traditional smoking cessation program in helping smokers quit, reduce cigarette exposure, lower exposure to carcinogens, and reduce risk for death and hospitalizations. If our hypothesis is correct, this program could dramatically alter treatment choices for the millions of smokers in the United States with COPD that have been frustrated in their attempts to quit.
Interventions
OTHERStandard Smoking Cessation
Participants in the standard smoking cessation (SC) arm will receive a standard approach to smoking cessation, including smoking cessation counseling supplemented with 10 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) if they are willing to make a quit attempt.
OTHERExtended Nicotine Replacement Therapy
Participants in the guided maintenance therapy (GMT) arm will receive counseling focused on medication adherence and smoking reduction plus up to 52 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) regardless of their interest in quitting.
DRUGNicotine replacement therapy
Sponsors
Patient-Centered Outcomes Research Institute
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Physician-diagnosed COPD * Smoke 5 or more cigarettes/day * Smoke cigarettes on 25 or more of the last 30 days * Speak either English or Spanish * Willing to take nicotine replacement therapy for up to 1 year and participate in study procedures
Exclusion criteria
* Reside in a facility that does not allow smoking * Don't have an address and telephone * Unstable cardiac condition (e.g. unstable angina or myocardial infarction in the past 30 days) * Pregnant or breastfeeding * Terminal illness with less than 12 month life expectancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Abstinence (Point Prevalent) | Month 12 | 7-day point prevalent abstinence at 12 months, confirmed by exhaled CO \<=10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quit Attempts | Month 3, Month 6, Month 12 | Number of self-reported quit attempts over one year. At Month 3 and Month 6, participants reported the number of quit attempts in the last 3 months. At Month 12, participants reported the number of quit attempts in the last 6 months. |
| Average Cigarettes Per Day | Month 3, Month 6, Month 12 | Average number of cigarettes per day over one year. Participants were asked at Month 3, Month 6, and Month 12 During the past 7 days, on those days that you smoked, what was the average number of cigarettes or little cigars smoked per day? |
| Carbon Monoxide Exposure | Month 3, Month 6, Month 12 | Carbon monoxide (CO) exposure over 12 months. At Month 3, Month 6, and Month 12, participants completed an expired carbon monoxide laboratory test, which measured CO in parts per million. |
| Carcinogen Exposure | Month 3, Month 6, Month 12 | Creatinine-adjusted NNAL (4-(methylnitrosamino)-1-(3)pyridyl-1-butanol)) exposure over 12 months. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and NNAL. |
| Respiratory Function | Month 12 | Change in respiratory function, as measured by spirometry (FEV1), at 12 months post-randomization. |
| Respiratory Symptoms | Month 3, Month 6, Month 12 | Respiratory symptoms as measured by the COPD Assessment Test (CAT) respiratory questionnaire. Participants completed this 8-item assessment at Month 3, Month 6, and Month 12. Scores range from 0 to 40, with higher levels indicating higher impact of COPD on well-being and daily life. |
| Respiratory-related Hospital Visits | Month 3, Month 6, Month 12 | Number of respiratory-related hospital admissions and emergency room visits. Participants were asked how many times they had visited the ED or were admitted to the hospital for respiratory-related problems at Month 3, Month 6, and Month 12 |
| Sustained Abstinence | Month 6 through Month 12 | 6 month sustained abstinence as measured by self-report at 6 and 12 months and confirmed by CO at 6 and 12 months. Participants who were confirmed as non-smokers by carbon monoxide (CO) at both Month 6 and Month 12 were considered to have 6-month sustained abstinence. |
| 7-day Abstinence | Month 3, Month 6, Month 12 | Self-reported and biochemically verified 7-day abstinence. Participants were asked at Month 3, Month 6, and Month 12, Have you smoked any cigarettes or little cigars, even a puff, in the past 7 days? They also completed an exhaled carbon monoxide lab test at Month 3, 6 and 12. Biochemical verification= exhaled CO \<=10 ppm. Month 12 biochemically verified abstinence is the primary outcome, and is not reported in this table. |
| Cotinine | Month 3, Month 6, Month 12 | Cotinine over 12 months, adjusted for creatinine. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and cotinine. |
| Average Cigarettes Per Day (Continued Smokers Only) | Month 3, Month 6, Month 12 | Average number of cigarettes per day over one year, among continued smokers. All participants were asked During the past 7 days, on those days that you smoked, what was the average number of cigarettes smoked per day? at Month 3, Month 6, and Month 12. This analysis looks at the number of cigarettes per day among participants who were still smoking. |
| Carbon Monoxide Exposure (Continued Smokers Only) | Month 3, Month 6, Month 12 | Carbon monoxide (CO) exposure over 12 months. At Month 3, Month 6, and Month 12, participants completed an expired carbon monoxide laboratory test, which measured CO in parts per million. This analysis looks at CO among those continuing to smoke. |
| Carcinogen Exposure (Continued Smokers Only) | Month 3, Month 6, Month 12 | Creatinine-adjusted NNAL (4-(methylnitrosamino)-1-(3)pyridyl-1-butanol)) exposure over 12 months. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and NNAL. This analysis looks at NNAL among continuing smokers only. |
| Cotinine (Continued Smokers Only) | Month 3, Month 6, Month 12 | Cotinine over 12 months, adjusted for creatinine. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and cotinine. This analysis looks at NNAL among continuing smokers only. |
| Cardiac-related Hospital Visits | Month 3, Month 6, Month 12 | Number of cardiac-related hospital admissions and emergency room visits. Participants were asked how many times they had visited the ED or were admitted to the hospital for cardiac-related problems at Month 3, Month 6, and Month 12. |
Countries
United States
Participant flow
Pre-assignment details
667 Screened for Eligibility 153 Did not meet inclusion criteria 116 Refused to participate 398 Randomized
Participants by arm
| Arm | Count |
|---|---|
| Standard Smoking Cessation Participants in the standard smoking cessation (SC) arm will receive a standard approach to smoking cessation, including smoking cessation counseling supplemented with 10 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) if they are willing to make a quit attempt. | 198 |
| Extended Nicotine Replacement Therapy Participants in the guided maintenance therapy (GMT) arm will receive counseling focused on medication adherence and smoking reduction plus up to 52 weeks of combination nicotine replacement therapy (NRT) (nicotine patch plus choice of gum or lozenge) regardless of their interest in quitting. | 200 |
| Total | 398 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 3 |
Baseline characteristics
| Characteristic | Standard Smoking Cessation | Extended Nicotine Replacement Therapy | Total |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 8.66 | 55.7 years STANDARD_DEVIATION 9.88 | 55.9 years STANDARD_DEVIATION 9.29 |
| Carbon Monoxide Exposure | 22.2 parts per million STANDARD_DEVIATION 13.12 | 22.7 parts per million STANDARD_DEVIATION 14.48 | 22.5 parts per million STANDARD_DEVIATION 13.81 |
| Carcinogen Exposure (Creatinine Adjusted NNAL) | 451.3 pg/mg STANDARD_DEVIATION 422.74 | 507.4 pg/mg STANDARD_DEVIATION 764.95 | 475.0 pg/mg STANDARD_DEVIATION 604.41 |
| Cigarettes Smoked per Day | 22.1 cigarettes per day STANDARD_DEVIATION 11.87 | 24.0 cigarettes per day STANDARD_DEVIATION 12.58 | 23.0 cigarettes per day STANDARD_DEVIATION 12.26 |
| Cotinine | 2395.8 ng/mg of creatinine STANDARD_DEVIATION 2184.8 | 2447.2 ng/mg of creatinine STANDARD_DEVIATION 2433.58 | 2421.6 ng/mg of creatinine STANDARD_DEVIATION 2310.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 190 Participants | 195 Participants | 385 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of cardiac-related hospital admissions and ED visits in the past 12 months 0 Visits | 178 Participants | 171 Participants | 349 Participants |
| Number of cardiac-related hospital admissions and ED visits in the past 12 months 1 Visit | 7 Participants | 17 Participants | 24 Participants |
| Number of cardiac-related hospital admissions and ED visits in the past 12 months 2 or more Visits | 13 Participants | 12 Participants | 25 Participants |
| Number of Quit Attempts in the Past 12 Months | 2.2 number of quit attempts STANDARD_DEVIATION 5.09 | 1.9 number of quit attempts STANDARD_DEVIATION 4.29 | 2.1 number of quit attempts STANDARD_DEVIATION 4.7 |
| Number of respiratory-related hospital admissions and ED visits in the past 12 months 0 Visits | 122 Participants | 134 Participants | 256 Participants |
| Number of respiratory-related hospital admissions and ED visits in the past 12 months 1 Visit | 30 Participants | 36 Participants | 66 Participants |
| Number of respiratory-related hospital admissions and ED visits in the past 12 months 2 or more Visits | 46 Participants | 30 Participants | 76 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 35 Participants | 82 Participants |
| Race (NIH/OMB) More than one race | 35 Participants | 42 Participants | 77 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 113 Participants | 123 Participants | 236 Participants |
| Region of Enrollment United States | 198 participants | 200 participants | 398 participants |
| Respiratory Function | 57.3 % of predicted STANDARD_DEVIATION 18.61 | 56.7 % of predicted STANDARD_DEVIATION 21.03 | 57.0 % of predicted STANDARD_DEVIATION 19.84 |
| Respiratory Symptoms | 21.1 units on a scale STANDARD_DEVIATION 8.82 | 22.9 units on a scale STANDARD_DEVIATION 8.32 | 22.0 units on a scale STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 111 Participants | 127 Participants | 238 Participants |
| Sex: Female, Male Male | 87 Participants | 73 Participants | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 198 | 3 / 200 |
| other Total, other adverse events | 97 / 198 | 163 / 200 |
| serious Total, serious adverse events | 9 / 198 | 8 / 200 |
Outcome results
Primary
Smoking Abstinence (Point Prevalent)
7-day point prevalent abstinence at 12 months, confirmed by exhaled CO \<=10
Time frame: Month 12
Population: n=4 deceased participants were excluded from analysis. Missing values were counted as smokers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Smoking Cessation | Smoking Abstinence (Point Prevalent) | 23 Participants |
| Extended Nicotine Replacement Therapy | Smoking Abstinence (Point Prevalent) | 24 Participants |
p-value: 0.88Chi-squared
Secondary
7-day Abstinence
Self-reported and biochemically verified 7-day abstinence. Participants were asked at Month 3, Month 6, and Month 12, Have you smoked any cigarettes or little cigars, even a puff, in the past 7 days? They also completed an exhaled carbon monoxide lab test at Month 3, 6 and 12. Biochemical verification= exhaled CO \<=10 ppm. Month 12 biochemically verified abstinence is the primary outcome, and is not reported in this table.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants were excluded from analysis. Missing responses were coded as smokers.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Smoking Cessation | 7-day Abstinence | Month 3, biochemically verified | 25 Participants |
| Standard Smoking Cessation | 7-day Abstinence | Month 6, biochemically verified | 25 Participants |
| Standard Smoking Cessation | 7-day Abstinence | Month 6, self-report | 28 Participants |
| Standard Smoking Cessation | 7-day Abstinence | Month 12, self-report | 25 Participants |
| Standard Smoking Cessation | 7-day Abstinence | Month 3, self-report | 27 Participants |
| Extended Nicotine Replacement Therapy | 7-day Abstinence | Month 12, self-report | 28 Participants |
| Extended Nicotine Replacement Therapy | 7-day Abstinence | Month 3, self-report | 16 Participants |
| Extended Nicotine Replacement Therapy | 7-day Abstinence | Month 3, biochemically verified | 14 Participants |
| Extended Nicotine Replacement Therapy | 7-day Abstinence | Month 6, self-report | 20 Participants |
| Extended Nicotine Replacement Therapy | 7-day Abstinence | Month 6, biochemically verified | 19 Participants |
Comparison: Month 3 self-reported abstinencep-value: 0.08Chi-squared
Comparison: Month 3 biochemically verified abstinencep-value: 0.06Chi-squared
Comparison: Month 6, self-reported abstinencep-value: 0.22Chi-squared
Comparison: Month 6, biochemically verified abstinencep-value: 0.34Chi-squared
Comparison: Month 12, self-reported abstinencep-value: 0.66Chi-squared
Secondary
Average Cigarettes Per Day
Average number of cigarettes per day over one year. Participants were asked at Month 3, Month 6, and Month 12 During the past 7 days, on those days that you smoked, what was the average number of cigarettes or little cigars smoked per day?
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Average Cigarettes Per Day | Month 3 | 7.9 cigarettes per day | Standard Deviation 8.64 |
| Standard Smoking Cessation | Average Cigarettes Per Day | Month 6 | 8.1 cigarettes per day | Standard Deviation 8.52 |
| Standard Smoking Cessation | Average Cigarettes Per Day | Month 12 | 8.5 cigarettes per day | Standard Deviation 7.84 |
| Extended Nicotine Replacement Therapy | Average Cigarettes Per Day | Month 3 | 10.5 cigarettes per day | Standard Deviation 8.64 |
| Extended Nicotine Replacement Therapy | Average Cigarettes Per Day | Month 6 | 9.1 cigarettes per day | Standard Deviation 9.45 |
| Extended Nicotine Replacement Therapy | Average Cigarettes Per Day | Month 12 | 8.1 cigarettes per day | Standard Deviation 8.33 |
p-value: 0.05Mixed Models Analysis
Secondary
Average Cigarettes Per Day (Continued Smokers Only)
Average number of cigarettes per day over one year, among continued smokers. All participants were asked During the past 7 days, on those days that you smoked, what was the average number of cigarettes smoked per day? at Month 3, Month 6, and Month 12. This analysis looks at the number of cigarettes per day among participants who were still smoking.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis, non-smokers at each time point excluded
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Average Cigarettes Per Day (Continued Smokers Only) | Month 3 | 8.7 cigarettes per day | Standard Deviation 8.84 |
| Standard Smoking Cessation | Average Cigarettes Per Day (Continued Smokers Only) | Month 6 | 9.1 cigarettes per day | Standard Deviation 8.62 |
| Standard Smoking Cessation | Average Cigarettes Per Day (Continued Smokers Only) | Month 12 | 9.7 cigarettes per day | Standard Deviation 7.64 |
| Extended Nicotine Replacement Therapy | Average Cigarettes Per Day (Continued Smokers Only) | Month 3 | 11.4 cigarettes per day | Standard Deviation 8.53 |
| Extended Nicotine Replacement Therapy | Average Cigarettes Per Day (Continued Smokers Only) | Month 6 | 9.9 cigarettes per day | Standard Deviation 9.52 |
| Extended Nicotine Replacement Therapy | Average Cigarettes Per Day (Continued Smokers Only) | Month 12 | 9.3 cigarettes per day | Standard Deviation 8.27 |
p-value: 0.05Mixed Models Analysis
Secondary
Carbon Monoxide Exposure
Carbon monoxide (CO) exposure over 12 months. At Month 3, Month 6, and Month 12, participants completed an expired carbon monoxide laboratory test, which measured CO in parts per million.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Carbon Monoxide Exposure | Month 3 | 15.0 parts per million (ppm) | Standard Deviation 12.62 |
| Standard Smoking Cessation | Carbon Monoxide Exposure | Month 6 | 14.6 parts per million (ppm) | Standard Deviation 11.85 |
| Standard Smoking Cessation | Carbon Monoxide Exposure | Month 12 | 15.5 parts per million (ppm) | Standard Deviation 11.14 |
| Extended Nicotine Replacement Therapy | Carbon Monoxide Exposure | Month 3 | 17.4 parts per million (ppm) | Standard Deviation 13.69 |
| Extended Nicotine Replacement Therapy | Carbon Monoxide Exposure | Month 6 | 15.4 parts per million (ppm) | Standard Deviation 12.58 |
| Extended Nicotine Replacement Therapy | Carbon Monoxide Exposure | Month 12 | 13.8 parts per million (ppm) | Standard Deviation 11.14 |
p-value: 0.05Mixed Models Analysis
Secondary
Carbon Monoxide Exposure (Continued Smokers Only)
Carbon monoxide (CO) exposure over 12 months. At Month 3, Month 6, and Month 12, participants completed an expired carbon monoxide laboratory test, which measured CO in parts per million. This analysis looks at CO among those continuing to smoke.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis, non-smokers at each time point excluded
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Carbon Monoxide Exposure (Continued Smokers Only) | Month 3 | 16.4 parts per million (ppm) | Standard Deviation 12.56 |
| Standard Smoking Cessation | Carbon Monoxide Exposure (Continued Smokers Only) | Month 6 | 16.0 parts per million (ppm) | Standard Deviation 11.68 |
| Standard Smoking Cessation | Carbon Monoxide Exposure (Continued Smokers Only) | Month 12 | 17.4 parts per million (ppm) | Standard Deviation 10.57 |
| Extended Nicotine Replacement Therapy | Carbon Monoxide Exposure (Continued Smokers Only) | Month 3 | 18.8 parts per million (ppm) | Standard Deviation 13.23 |
| Extended Nicotine Replacement Therapy | Carbon Monoxide Exposure (Continued Smokers Only) | Month 6 | 17.0 parts per million (ppm) | Standard Deviation 12.49 |
| Extended Nicotine Replacement Therapy | Carbon Monoxide Exposure (Continued Smokers Only) | Month 12 | 15.8 parts per million (ppm) | Standard Deviation 10.73 |
p-value: 0.08Mixed Models Analysis
Secondary
Carcinogen Exposure
Creatinine-adjusted NNAL (4-(methylnitrosamino)-1-(3)pyridyl-1-butanol)) exposure over 12 months. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and NNAL.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants were excluded from analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Carcinogen Exposure | Month 3 | 279.0 pg/mg creatinine | Standard Deviation 353.42 |
| Standard Smoking Cessation | Carcinogen Exposure | Month 6 | 178.2 pg/mg creatinine | Standard Deviation 221.26 |
| Standard Smoking Cessation | Carcinogen Exposure | Month 12 | 190.4 pg/mg creatinine | Standard Deviation 233.22 |
| Extended Nicotine Replacement Therapy | Carcinogen Exposure | Month 3 | 320.1 pg/mg creatinine | Standard Deviation 350.59 |
| Extended Nicotine Replacement Therapy | Carcinogen Exposure | Month 6 | 186.0 pg/mg creatinine | Standard Deviation 236.21 |
| Extended Nicotine Replacement Therapy | Carcinogen Exposure | Month 12 | 183.5 pg/mg creatinine | Standard Deviation 223.94 |
p-value: 0.39Mixed Models Analysis
Secondary
Carcinogen Exposure (Continued Smokers Only)
Creatinine-adjusted NNAL (4-(methylnitrosamino)-1-(3)pyridyl-1-butanol)) exposure over 12 months. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and NNAL. This analysis looks at NNAL among continuing smokers only.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants were excluded from analysis, non-smokers at each time point excluded
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Carcinogen Exposure (Continued Smokers Only) | Month 3 | 314.6 pg/mg creatinine | Standard Deviation 373.23 |
| Standard Smoking Cessation | Carcinogen Exposure (Continued Smokers Only) | Month 6 | 219.8 pg/mg creatinine | Standard Deviation 236.3 |
| Standard Smoking Cessation | Carcinogen Exposure (Continued Smokers Only) | Month 12 | 257.0 pg/mg creatinine | Standard Deviation 234.83 |
| Extended Nicotine Replacement Therapy | Carcinogen Exposure (Continued Smokers Only) | Month 3 | 337.6 pg/mg creatinine | Standard Deviation 363.8 |
| Extended Nicotine Replacement Therapy | Carcinogen Exposure (Continued Smokers Only) | Month 6 | 217.1 pg/mg creatinine | Standard Deviation 251.82 |
| Extended Nicotine Replacement Therapy | Carcinogen Exposure (Continued Smokers Only) | Month 12 | 247.5 pg/mg creatinine | Standard Deviation 230.64 |
p-value: 0.77Mixed Models Analysis
Secondary
Cardiac-related Hospital Visits
Number of cardiac-related hospital admissions and emergency room visits. Participants were asked how many times they had visited the ED or were admitted to the hospital for cardiac-related problems at Month 3, Month 6, and Month 12.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 3 | 1 Visit | 7 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 6 | 2 or more Visits | 0 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 6 | 0 Visits | 171 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 12 | 0 Visits | 175 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 3 | 2 or more Visits | 1 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 12 | 1 Visit | 8 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 6 | 1 Visit | 10 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 12 | 2 or more Visits | 2 Participants |
| Standard Smoking Cessation | Cardiac-related Hospital Visits | Month 3 | 0 Visits | 181 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 12 | 2 or more Visits | 3 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 3 | 0 Visits | 185 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 3 | 1 Visit | 6 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 3 | 2 or more Visits | 0 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 6 | 0 Visits | 180 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 6 | 1 Visit | 4 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 6 | 2 or more Visits | 1 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 12 | 0 Visits | 167 Participants |
| Extended Nicotine Replacement Therapy | Cardiac-related Hospital Visits | Month 12 | 1 Visit | 12 Participants |
Secondary
Cotinine
Cotinine over 12 months, adjusted for creatinine. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and cotinine.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants were excluded from analysis
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Cotinine | Month 3 | 2652.5 ng/mg creatinine | Standard Deviation 2675.18 |
| Standard Smoking Cessation | Cotinine | Month 6 | 2390.7 ng/mg creatinine | Standard Deviation 2842.07 |
| Standard Smoking Cessation | Cotinine | Month 12 | 2159.0 ng/mg creatinine | Standard Deviation 2989.46 |
| Extended Nicotine Replacement Therapy | Cotinine | Month 3 | 3378.1 ng/mg creatinine | Standard Deviation 3182 |
| Extended Nicotine Replacement Therapy | Cotinine | Month 6 | 3342.3 ng/mg creatinine | Standard Deviation 3282.48 |
| Extended Nicotine Replacement Therapy | Cotinine | Month 12 | 2363.7 ng/mg creatinine | Standard Deviation 2988.16 |
p-value: 0.0149Mixed Models Analysis
Secondary
Cotinine (Continued Smokers Only)
Cotinine over 12 months, adjusted for creatinine. At Month 3, Month 6, and Month 12, participants provided a urine sample that was used to assess their level of urinary creatinine and cotinine. This analysis looks at NNAL among continuing smokers only.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants were excluded from analysis, non-smokers at each time point excluded
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Cotinine (Continued Smokers Only) | Month 6 | 2850.7 ng/mg creatinine | Standard Deviation 2645.5 |
| Standard Smoking Cessation | Cotinine (Continued Smokers Only) | Month 3 | 2771.2 ng/mg creatinine | Standard Deviation 2774.24 |
| Standard Smoking Cessation | Cotinine (Continued Smokers Only) | Month 12 | 2733.9 ng/mg creatinine | Standard Deviation 2532.32 |
| Extended Nicotine Replacement Therapy | Cotinine (Continued Smokers Only) | Month 6 | 3502.2 ng/mg creatinine | Standard Deviation 2978.67 |
| Extended Nicotine Replacement Therapy | Cotinine (Continued Smokers Only) | Month 3 | 3305.8 ng/mg creatinine | Standard Deviation 2859.9 |
| Extended Nicotine Replacement Therapy | Cotinine (Continued Smokers Only) | Month 12 | 2782.7 ng/mg creatinine | Standard Deviation 2583.6 |
p-value: 0.0918Mixed Models Analysis
Secondary
Quit Attempts
Number of self-reported quit attempts over one year. At Month 3 and Month 6, participants reported the number of quit attempts in the last 3 months. At Month 12, participants reported the number of quit attempts in the last 6 months.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Quit Attempts | Month 12 | 5.7 number of quit attempts | Standard Deviation 8.59 |
| Standard Smoking Cessation | Quit Attempts | Month 3 | 4.6 number of quit attempts | Standard Deviation 6.54 |
| Standard Smoking Cessation | Quit Attempts | Month 6 | 4.5 number of quit attempts | Standard Deviation 6.86 |
| Extended Nicotine Replacement Therapy | Quit Attempts | Month 6 | 4.8 number of quit attempts | Standard Deviation 8.97 |
| Extended Nicotine Replacement Therapy | Quit Attempts | Month 3 | 3.7 number of quit attempts | Standard Deviation 5.48 |
| Extended Nicotine Replacement Therapy | Quit Attempts | Month 12 | 6.2 number of quit attempts | Standard Deviation 11.31 |
p-value: 0.4Mixed Models Analysis
Secondary
Respiratory Function
Change in respiratory function, as measured by spirometry (FEV1), at 12 months post-randomization.
Time frame: Month 12
Population: n=4 deceased participants excluded from analysis. Participants with missing data excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Smoking Cessation | Respiratory Function | 55.4 % of predicted | Standard Deviation 19.25 |
| Extended Nicotine Replacement Therapy | Respiratory Function | 56.8 % of predicted | Standard Deviation 19.78 |
p-value: 0.42t-test, 1 sided
Secondary
Respiratory-related Hospital Visits
Number of respiratory-related hospital admissions and emergency room visits. Participants were asked how many times they had visited the ED or were admitted to the hospital for respiratory-related problems at Month 3, Month 6, and Month 12
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 3 | 1 Visit | 11 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 6 | 2 or more Visits | 7 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 6 | 0 Visits | 152 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 12 | 0 Visits | 157 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 3 | 2 or more Visits | 2 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 12 | 1 Visit | 18 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 6 | 1 Visit | 22 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 12 | 2 or more Visits | 10 Participants |
| Standard Smoking Cessation | Respiratory-related Hospital Visits | Month 3 | 0 Visits | 176 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 12 | 2 or more Visits | 10 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 3 | 0 Visits | 169 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 3 | 1 Visit | 15 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 3 | 2 or more Visits | 7 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 6 | 0 Visits | 154 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 6 | 1 Visit | 24 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 6 | 2 or more Visits | 7 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 12 | 0 Visits | 153 Participants |
| Extended Nicotine Replacement Therapy | Respiratory-related Hospital Visits | Month 12 | 1 Visit | 20 Participants |
p-value: 0.06Mixed Models Analysis
Secondary
Respiratory Symptoms
Respiratory symptoms as measured by the COPD Assessment Test (CAT) respiratory questionnaire. Participants completed this 8-item assessment at Month 3, Month 6, and Month 12. Scores range from 0 to 40, with higher levels indicating higher impact of COPD on well-being and daily life.
Time frame: Month 3, Month 6, Month 12
Population: n=4 deceased participants excluded from analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Smoking Cessation | Respiratory Symptoms | Month 3 | 17.8 units on a scale | Standard Deviation 9.25 |
| Standard Smoking Cessation | Respiratory Symptoms | Month 6 | 17.9 units on a scale | Standard Deviation 9.48 |
| Standard Smoking Cessation | Respiratory Symptoms | Month 12 | 17.5 units on a scale | Standard Deviation 9.33 |
| Extended Nicotine Replacement Therapy | Respiratory Symptoms | Month 3 | 19.3 units on a scale | Standard Deviation 8.68 |
| Extended Nicotine Replacement Therapy | Respiratory Symptoms | Month 6 | 18.1 units on a scale | Standard Deviation 8.51 |
| Extended Nicotine Replacement Therapy | Respiratory Symptoms | Month 12 | 18.2 units on a scale | Standard Deviation 9.37 |
p-value: 0.27Mixed Models Analysis
Secondary
Sustained Abstinence
6 month sustained abstinence as measured by self-report at 6 and 12 months and confirmed by CO at 6 and 12 months. Participants who were confirmed as non-smokers by carbon monoxide (CO) at both Month 6 and Month 12 were considered to have 6-month sustained abstinence.
Time frame: Month 6 through Month 12
Population: n=4 deceased participants were excluded from analysis. Missing values were counted as smokers.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Smoking Cessation | Sustained Abstinence | 15 Participants |
| Extended Nicotine Replacement Therapy | Sustained Abstinence | 12 Participants |
p-value: 0.55Chi-squared