Nicotine Dependence
Conditions
Keywords
Nicotine addiction, Cigarette smoking, Smoking cessation, Zyban, Chantix, Nicotine patches, Nicotrol Inhaler, varenicline, bupropion
Brief summary
This study focuses on the first step in developing an algorithm for maximizing quit-smoking success based on an adaptive approach, which changes treatment from the initial nicotine replacement therapy (NRT) when that treatment alone may not be sufficient. These NRT non-responders are switched (in double-blind fashion) before the quit date to receive either varenicline alone or varenicline paired with bupropion. Some participants who would otherwise have failed at their quit smoking attempt could be rescued by switching to alternative pharmacotherapies. The proposed study will evaluate the combination treatment against varenicline alone in an adaptive trial design
Interventions
DRUGVarenicline
For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks.
DRUGBupropion
For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive bupropion at a dose of 150mg once per day. Subsequently, the dose will be 150mg twice per day, and will remain at that dose for the remainder of the 12 weeks.
DRUGNicotine patches
Nicotine Replacement Therapy Groups: 1. For smokers with high baseline carbon monoxide (CO): 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or 2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. Varenicline and varenicline in combination with bupropion groups: 1. For smokers with high baseline CO: 42 mg/24 h for 1 week 2. For smokers with low baseline CO: 21 mg/24 h for 1 week
DRUGNicotine Inhaler
Nicotine inhaler to use as needed after quit date
Sponsors
National Institute on Drug Abuse (NIDA)
Philip Morris USA, Inc.
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
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; * have an expired air CO reading assessed at screening of at least 10ppm; * express a desire to quit smoking within 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 with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg). * 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; * Currently symptomatic lung disorder/disease (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); * Migraine headaches that occur more frequently than once per week; * Recent, unexplained fainting spells; * 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; * Bulimia or anorexia; * Pregnant or nursing mothers; * Alcohol abuse; * Use of Opiate medications for pain or sleep in the past 14 days; * Significant adverse reaction to nicotine patches, nicotine inhalers, bupropion / Wellbutrin / Zyban or Chantix / Varenicline in the past. * 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); * Smokeless tobacco (chewing tobacco, snuff), cigars, pipes or e-cigarettes; * Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Four-week Continuous Abstinence From Cigarette Smoking | Study week 8 thru week 11 | The primary dependent measures will be continuous four-week abstinence from weeks 8-11 post target quit date, defined as a self-report of no smoking confirmed by expired air carbon monoxide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seven Day Point Abstinence From Cigarette Smoking | Six months post quit date | Secondary outcome will include point abstinence (no smoking in the previous 7-day) at 6 months post-quit. |
| Continuous Cigarette Abstinence From Quit Date | From Quit date to end of treatment (week 11) | Secondary outcome will include continuous abstinence from quit date to end of treatment (week 11). |
Countries
United States
Participant flow
Recruitment details
Recruitment began on 3/07/11 and ended on 11/30/12. Of the 702 subjects consented during this period, 218 were in our Charlotte, NC office, 157 were in our Durham, NC office, 151 were in our Raleigh, NC office and 176 were in our Winston-Salem, NC office. Only 349 subjects met all study criteria, and 22 discontinued prior to being assigned.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline This group will consist of smokers who, based on smoking behavior, DO NOT respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will receive varenicline.
Varenicline: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. | 109 |
| Nicotine Patches Only This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches(assessed at Session P2). They will continue to receive only nicotine patches.
Nicotine patches: Nicotine Replacement Therapy Groups:
1. For smokers with high baseline carbon monoxide (CO): 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.
Varenicline and varenicline in combination with bupropion groups:
1. For smokers with high baseline CO: 42 mg/24 h for 1 week
2. For smokers with low baseline CO: 21 mg/24 h for 1 week | 50 |
| Nicotine Patches With Nicotine Inhaler This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will continue to receive nicotine patches and will receive a nicotine inhaler to use as needed after their quit date.
Nicotine patches: Nicotine Replacement Therapy Groups:
1. For smokers with high baseline CO: 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.
Varenicline and varenicline in combination with bupropion groups:
1. For smokers with high baseline CO: 42 mg/24 h for 1 week
2. For smokers with low baseline CO: 21 mg/24 h for 1 week
Nicotine Inhaler: Nicotine inhaler to use as needed after quit date | 55 |
| Varenicline With Bupropion This group will consist of smokers who, based on smoking behavior, DO NOT respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will receive varenicline in combination with bupropion.
Varenicline: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks.
Bupropion: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive bupropion at a dose of 150mg once per day. Subsequently, the dose will be 150mg twice per day, and will remain at that dose for the remainder of the 12 weeks. | 113 |
| Dropped Prior to Condition Assignment These subjects discontinued study participation prior to being assigned to a condition. | 22 |
| Total | 349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 | 0 | 5 |
| Overall Study | Lack of Efficacy | 3 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 34 | 14 | 27 | 31 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 16 | 8 | 8 | 23 |
Baseline characteristics
| Characteristic | Varenicline | Nicotine Patches Only | Nicotine Patches With Nicotine Inhaler | Varenicline With Bupropion | Dropped Prior to Condition Assignment | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 49 Participants | 54 Participants | 113 Participants | 22 Participants | 347 Participants |
| Age, Continuous | 45.58 years STANDARD_DEVIATION 11.39 | 45.20 years STANDARD_DEVIATION 10.56 | 42.09 years STANDARD_DEVIATION 12.22 | 44.22 years STANDARD_DEVIATION 10.47 | 44.77 years STANDARD_DEVIATION 11.28 | 44.42 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants | 49 Participants | 54 Participants | 111 Participants | 21 Participants | 340 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 20 Participants | 19 Participants | 41 Participants | 9 Participants | 121 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 71 Participants | 29 Participants | 31 Participants | 68 Participants | 11 Participants | 210 Participants |
| Region of Enrollment United States | 109 participants | 50 participants | 55 participants | 113 participants | 22 participants | 349 participants |
| Sex: Female, Male Female | 63 Participants | 30 Participants | 34 Participants | 58 Participants | 10 Participants | 195 Participants |
| Sex: Female, Male Male | 46 Participants | 20 Participants | 21 Participants | 55 Participants | 12 Participants | 154 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 76 / 109 | 33 / 50 | 38 / 55 | 80 / 113 | 0 / 22 |
| serious Total, serious adverse events | 0 / 109 | 1 / 50 | 0 / 55 | 0 / 113 | 0 / 22 |
Outcome results
Primary
Four-week Continuous Abstinence From Cigarette Smoking
The primary dependent measures will be continuous four-week abstinence from weeks 8-11 post target quit date, defined as a self-report of no smoking confirmed by expired air carbon monoxide.
Time frame: Study week 8 thru week 11
Population: 1 subject from varenicline group excluded from analysis due to pregnancy. 1 subject from Nicotine Patches only group excluded due to meeting an exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Four-week Continuous Abstinence From Cigarette Smoking | 25.93 percentage of participants |
| Nicotine Patches Only | Four-week Continuous Abstinence From Cigarette Smoking | 46.94 percentage of participants |
| Nicotine Patches With Nicotine Inhaler | Four-week Continuous Abstinence From Cigarette Smoking | 43.64 percentage of participants |
| Varenicline With Bupropion | Four-week Continuous Abstinence From Cigarette Smoking | 39.82 percentage of participants |
Secondary
Continuous Cigarette Abstinence From Quit Date
Secondary outcome will include continuous abstinence from quit date to end of treatment (week 11).
Time frame: From Quit date to end of treatment (week 11)
Population: 1 subject from varenicline group excluded from analysis due to pregnancy. 1 subject from Nicotine Patches only group excluded due to meeting an exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Continuous Cigarette Abstinence From Quit Date | 9 participants |
| Nicotine Patches Only | Continuous Cigarette Abstinence From Quit Date | 13 participants |
| Nicotine Patches With Nicotine Inhaler | Continuous Cigarette Abstinence From Quit Date | 15 participants |
| Varenicline With Bupropion | Continuous Cigarette Abstinence From Quit Date | 17 participants |
Secondary
Seven Day Point Abstinence From Cigarette Smoking
Secondary outcome will include point abstinence (no smoking in the previous 7-day) at 6 months post-quit.
Time frame: Six months post quit date
Population: 1 subject from varenicline group excluded from analysis due to pregnancy. 1 subject from Nicotine Patches only group excluded due to meeting an exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Seven Day Point Abstinence From Cigarette Smoking | 18 participants |
| Nicotine Patches Only | Seven Day Point Abstinence From Cigarette Smoking | 12 participants |
| Nicotine Patches With Nicotine Inhaler | Seven Day Point Abstinence From Cigarette Smoking | 6 participants |
| Varenicline With Bupropion | Seven Day Point Abstinence From Cigarette Smoking | 29 participants |