Smoking Cessation
Conditions
Keywords
Smoking Cessation, Chantix, varenicline, Nicotine Replacement Therapy, Nicotine Patches, Zyban, bupropion, Quit Smoking
Brief summary
Nicotine replacement therapy (NRT) is a well-tolerated and efficacious smoking cessation treatment, and yet many smokers fail to quit using NRT. Many of these smokers may benefit from prescription treatment alternatives, including Zyban or Chantix. In this study, the investigators propose to develop and evaluate a stepped-care treatment algorithm that would evaluate whether smokers who receive treatment with NRT should be supplemented with Zyban or switched to Chantix only based on: 1) their initial response to NRT; and 2) individual genetic factors found to predict smoking cessation in other studies evaluating these treatments. This study is a continuation of our previous studies showing that abstinence rates can be increased by starting nicotine patch therapy two weeks before the quit date. The investigators will provide pre-cessation NRT to all participants initially. Those who do not show a favorable response on early indicators of success (e.g., smoking in the first week after the target quit-smoking date) will receive rescue treatment by having their NRT treatment supplemented with Zyban , by being switched to treatment with Chantix or will remain on NRT (control). The investigators hypothesize that Rescue treatment with Zyban in combination with NRT or Chantix will increase success rates over leaving subjects on NRT when they are NRT insufficient responders, i.e. they have shown an unfavorable response to NRT in the first week pre-quit or the first week post-quit.
Interventions
DRUGNicotine Patches
21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.
DRUGNicotine patches, then bupropion & nicotine patches (Pre-Quit)
21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.
DRUGNicotine patches, then varenicline (Pre-Quit)
21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks)
DRUGNicotine patches, then nicotine patches (Pre-Quit)
21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.
DRUGNicotine patches, then bupropion & nicotine patches (Post-Quit)
21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.
DRUGNicotine patches, then varenicline (Post-Quit)
21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks)
DRUGNicotine patches, then nicotine patches (Post-Quit)
21mg (1 patch) or 42mg (2 patches) nicotine patches for first seven weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.
Sponsors
Philip Morris USA, Inc.
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years old * smoked an average of at least 10 cigarettes per day for three cumulative years of a brand that delivers (by Federal Trade Commission rated yields) at least 0.5mg nicotine * expired carbon monoxide reading of at least 15ppm * express a desire to quit smoking in the next 30 days
Exclusion criteria
* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100. * Hypotension (systolic \<90 mm Hg, diastolic \<60 mm Hg). * Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety. * Coronary heart disease; * Lifetime history of heart attack; * Cardiac rhythm disorder (irregular heart rhythm); * Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source); * Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure); * History of skin allergy; * Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds); * Liver or kidney disorder (except kidney stones, gallstones); * Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn; * Active ulcers in the past 30 days; * Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma); * Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder); * History of migraine headaches in the past 5 years; * History of fainting; * Problems giving blood samples; * Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%); * Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer); * Other major medical condition; * Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and ADHD); * Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide; * Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 (Thoughts that you would be better off dead, or of hurting yourself in some way) will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment; * Bulimia or anorexia; * Pregnant or nursing mothers; * Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive), * Experimental (investigational) drugs; * Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed) * Smokeless tobacco (chewing tobacco, snuff), cigars or pipes; * Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid. * Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire will be used to assess alcohol abuse. Potential participants will be asked the first two questions on the AUDIT questionnaire during the phone screen. If the person scores 4 on both questions, a screening appointment will not be scheduled. During the screening session the entire AUDIT questionnaire will be administered. Females who score greater than or equal to 13 and males who score greater than or equal to 15 will be excluded from the study. * Significant adverse reaction to Wellbutrin / Zyban or Chantix / Varenicline in the past
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | weeks 8-11 after quit date | A self report of no cigarettes smoked confirmed by expired air carbon monoxide of \<=10ppm was the criterion for abstinence. |
Secondary
| Measure | Time frame |
|---|---|
| Abstinence (7 Days) at 6 Months. | point abstinence (7 days) at 6 months post-quit date |
| Continuous Abstinence From Smoking at 6 Months Post Quit. | continuous abstinence at 6 months post quit day |
Countries
United States
Participant flow
Recruitment details
Study started June 2009 and ended April 2011 and was conducted at Duke University Medical Center.
Pre-assignment details
All enrollees began nicotine patches & those who didn't show a \>50% reduction in expired air carbon monoxide (CO) at 1 week (1 week before the target quit date) or who lapsed in the 1st week after their quit date were randomized to one of 6 groups. The 7th group - Nicotine Replacement Therapy (NRT) Responders were excluded from this randomization.
Participants by arm
| Arm | Count |
|---|---|
| NRT Responder Participants in this group showed both a \>50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment and did not lapse during their 1st week after quitting. | 132 |
| Pre-Quit Randomization to Bupropion + NRT Participants not showing a \>50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use Zyban (bupropion) in combination with nicotine patches. | 109 |
| Pre-Quit Randomization to Varenicline Participants not showing a \>50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment, who are randomly assigned at week 2 to use varenicline. | 112 |
| Pre-Quit Randomization to NRT Participants not showing a \>50% decrease in expired air CO during the 1st week of pre-cessation nicotine patch treatment,who are randomly assigned at week 2 to use continued use of nicotine patches. | 114 |
| Post-Quit Randomization to Bupropion + NRT Participants who did show \>50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use of bupropion in combination with nicotine patches. | 34 |
| Post-Quit Randomized to Varenicline Participants who did show \>50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use varenicline. | 36 |
| Post-Quit Randomized to NRT Participants who did show \>50% decrease in expired air CO on pre-cessation NRT but who lapsed during the first week post quit date, who are randomly assigned to use nicotine patches. | 35 |
| Withdrew Prior to Randomization These subjects dropped from study participation after the first study session; therefore, they were never randomized into one of the study groups. | 34 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrew or Lost to Follow-Up | 61 | 63 | 62 | 68 | 24 | 16 | 16 | 34 |
Baseline characteristics
| Characteristic | Pre-Quit Randomization to Bupropion + NRT | Pre-Quit Randomization to Varenicline | Pre-Quit Randomization to NRT | Post-Quit Randomization to Bupropion + NRT | NRT Responder | Post-Quit Randomized to Varenicline | Post-Quit Randomized to NRT | Withdrew Prior to Randomization | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 108 Participants | 112 Participants | 113 Participants | 34 Participants | 129 Participants | 36 Participants | 35 Participants | 34 Participants | 601 Participants |
| Age Continuous | 46.0 years STANDARD_DEVIATION 10.8 | 44.7 years STANDARD_DEVIATION 10.7 | 44.3 years STANDARD_DEVIATION 10.8 | 43.1 years STANDARD_DEVIATION 11.6 | 43.6 years STANDARD_DEVIATION 10.2 | 44.1 years STANDARD_DEVIATION 11.2 | 40.8 years STANDARD_DEVIATION 12.8 | 40.7 years STANDARD_DEVIATION 10.1 | 44.3 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment United States | 109 participants | 112 participants | 114 participants | 34 participants | 132 participants | 36 participants | 35 participants | 34 participants | 606 participants |
| Sex: Female, Male Female | 50 Participants | 49 Participants | 61 Participants | 17 Participants | 68 Participants | 17 Participants | 22 Participants | 16 Participants | 300 Participants |
| Sex: Female, Male Male | 59 Participants | 63 Participants | 53 Participants | 17 Participants | 64 Participants | 19 Participants | 13 Participants | 18 Participants | 306 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 88 / 132 | 74 / 109 | 64 / 112 | 85 / 114 | 31 / 34 | 27 / 36 | 28 / 35 |
| serious Total, serious adverse events | 3 / 132 | 4 / 109 | 3 / 112 | 2 / 114 | 2 / 34 | 1 / 36 | 1 / 35 |
Outcome results
Primary
Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment)
A self report of no cigarettes smoked confirmed by expired air carbon monoxide of \<=10ppm was the criterion for abstinence.
Time frame: weeks 8-11 after quit date
Population: All participants were included in the analyses except those dropping out prior to randomization points, those censored for taking contraindicated medications or failing to meet other inclusion criteria, and one death having no apparent relationship to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NRT Responder | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 59.2 percentage of subjects abstinent |
| Pre-Quit Randomization to Bupropion + NRT | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 28.3 percentage of subjects abstinent |
| Pre-Quit Randomization to Varenicline | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 23.3 percentage of subjects abstinent |
| Pre-Quit Randomization to NRT | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 16.0 percentage of subjects abstinent |
| Post-Quit Randomization to Bupropion + NRT | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 26.7 percentage of subjects abstinent |
| Post-Quit Randomized to Varenicline | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 37.1 percentage of subjects abstinent |
| Post-Quit Randomized to NRT | Continuous 4-week Abstinence From Smoking Between Weeks 8-11 After the Quit Date (Through the End of Treatment) | 26.7 percentage of subjects abstinent |
Secondary
Abstinence (7 Days) at 6 Months.
Time frame: point abstinence (7 days) at 6 months post-quit date
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NRT Responder | Abstinence (7 Days) at 6 Months. | 21.7 percentage of subjects |
| Pre-Quit Randomization to Bupropion + NRT | Abstinence (7 Days) at 6 Months. | 17.2 percentage of subjects |
| Pre-Quit Randomization to Varenicline | Abstinence (7 Days) at 6 Months. | 16.5 percentage of subjects |
| Pre-Quit Randomization to NRT | Abstinence (7 Days) at 6 Months. | 6.6 percentage of subjects |
| Post-Quit Randomization to Bupropion + NRT | Abstinence (7 Days) at 6 Months. | 10.0 percentage of subjects |
| Post-Quit Randomized to Varenicline | Abstinence (7 Days) at 6 Months. | 20.0 percentage of subjects |
| Post-Quit Randomized to NRT | Abstinence (7 Days) at 6 Months. | 13.3 percentage of subjects |
Secondary
Continuous Abstinence From Smoking at 6 Months Post Quit.
Time frame: continuous abstinence at 6 months post quit day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NRT Responder | Continuous Abstinence From Smoking at 6 Months Post Quit. | 20.0 percentage of subjects |
| Pre-Quit Randomization to Bupropion + NRT | Continuous Abstinence From Smoking at 6 Months Post Quit. | 13.1 percentage of subjects |
| Pre-Quit Randomization to Varenicline | Continuous Abstinence From Smoking at 6 Months Post Quit. | 5.8 percentage of subjects |
| Pre-Quit Randomization to NRT | Continuous Abstinence From Smoking at 6 Months Post Quit. | 5.8 percentage of subjects |
| Post-Quit Randomization to Bupropion + NRT | Continuous Abstinence From Smoking at 6 Months Post Quit. | 10.0 percentage of subjects |
| Post-Quit Randomized to Varenicline | Continuous Abstinence From Smoking at 6 Months Post Quit. | 14.3 percentage of subjects |
| Post-Quit Randomized to NRT | Continuous Abstinence From Smoking at 6 Months Post Quit. | 10.0 percentage of subjects |