Nicotine Dependence
Conditions
Keywords
Nicotine addiction, Cigarette smoking, Bupropion, Varenicline, Adaptive Approach, Nicotine Patch, Chantix
Brief summary
The purpose of this study is to assess an adaptive approach to smoking cessation pharmacotherapy. The protocol is designed to compare adaptive vs. standard approaches to two common smoking cessation pharmacotherapies - Varenicline (commonly known as Chantix) and the Nicotine Patch. The investigators hypothesize that participants allocated to adaptive therapy will show significantly higher biochemically confirmed 30-day continuous abstinence at 12 weeks post-Target Quit Day (TQD).
Detailed description
The purpose of this study is to assess an adaptive approach to smoking cessation pharmacotherapy. The protocol is designed to compare adaptive vs. standard approaches to two common smoking cessation pharmacotherapies (Varenicline and Nicotine Patch). The adaptive treatment approach provides the addition of Bupropion in the pre-quit period for participants who are not responding to initial treatment. Little is known about the adaptive use of Varenicline or Nicotine Patch, in which Bupropion is added to Varenicline or Patch for those who do not respond to one of these medications in a pre-quit treatment period. This study attempts to address these knowledge deficits. The study (N=300) is a double-blinded randomized placebo-controlled trial designed to compare biochemically-confirmed abstinence rates in smokers randomized to Varenicline Adaptive Protocol vs. Varenicline (N=150) and for comparison, Nicotine Patch Adaptive Protocol vs. Nicotine Patch (N=150). The Varenicline Adaptive Protocol is conducted by starting treatment with Varenicline 4 weeks prior to the quit day and following each participant's response to this pre-treatment medication. After 2 weeks, if the patient shows a reduction greater than 50% in cigarettes smoked per day, then the patient is considered to be a Varenicline responder and is continued on Varenicline alone out to 12-weeks post quit day. If the patient does not spontaneously decrease smoking in the pre-quit period by more than 50% cigarettes per day, the patient is considered to be a Varenicline non-responder and Bupropion is added to the Varenicline. For comparison, an identical protocol is used with nicotine patch vs. nicotine patch adaptive treatment. The study uses only FDA-approved medications: Varenicline, Nicotine Patch, Bupropion, and placebo controls. To pattern clinical practice, participants will be able to choose whether they would like to use a patch or Varenicline-based treatment. After choosing, however, they will be randomized to adaptive vs. non-adaptive version of that treatment. Placebo medications are matched throughout the study. Participants will be blinded to all medications. All participants will receive behavioral treatment including a single 40-minute visit with a medical provider. The study is designed to provide researchers and clinicians with a better understanding of how to use adaptive pharmacotherapy protocols to improve smoking cessation rates.
Interventions
BEHAVIORALVarenicline Standard Protocol
4 weeks pre-TQD: Start Placebo Varenicline 1 week prior to TQD: Switch to Active Varenicline 1 week prior to TQD: Start Placebo Bupropion Varenicline + Placebo Bupropion to 12 weeks post TQD
BEHAVIORALNicotine Patch Standard Protocol
4 weeks pre-TQD: Start Placebo Nicotine Patch TQD: Start active Nicotine Patch 1 week prior to TQD: Start Placebo Bupropion Nicotine Patch + Placebo Bupropion to 12 weeks post TQD
DRUGVarenicline Adaptive Protocol
VARENICLINE RESPONDER 4 weeks pre-TQD: Start Varenicline 2 weeks pre-TQD: DOES reduce cigs/day by \> 50% 1 week pre-TQD: Start Placebo Bupropion Varenicline + Placebo Bupropion to 12 weeks post TQD VARENICLINE NON-RESPONDER 4 weeks pre-TQD: Start Varenicline 2 weeks pre-TQD: DOES NOT reduce cigs/day by \> 50% 1 week pre-TQD: Start active Bupropion Varenicline + Bupropion to 12 weeks post TQD
DRUGNicotine Adaptive Protocol
NICOTINE PATCH RESPONDER 4 weeks pre-TQD: Start Patch 2 weeks pre-TQD: DOES reduce cigs/day by \> 50% 1 week pre-TQD: Start Placebo Bupropion Patch + Placebo Bupropion to 12 weeks post TQD NICOTINE PATCH NON-RESPONDER 4 weeks pre-TQD: Start Patch 2 weeks pre-TQD: DOES NOT reduce cigs/day by \> 50% 1 week pre-TQD: Start Bupropion Patch + Bupropion to 12 weeks post TQD
Sponsors
National Institute on Drug Abuse (NIDA)
Pfizer
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The study (N=300) is a double-blinded randomized placebo-controlled trial designed to compare biochemically-confirmed abstinence rates in smokers randomized to Varenicline Adaptive Protocol vs. Varenicline (N=150) and for comparison, Nicotine Patch Adaptive Protocol vs. Nicotine Patch (N=150).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older 2. Actively smoking 5 or more cigarettes per day for at least one year 3. Fluency in spoken and written English 4. Willing to set a quit date within 6 weeks 5. Access to a telephone 6. Willingness to take Varenicline OR nicotine patch (patient choice) 7. Willingness to take Bupropion
Exclusion criteria
1. Daily use of a second form of tobacco or nicotine (e.g. e-cigarettes, cigars, chewing tobacco, snuff). 2. Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline, Bupropion). 3. Report of pregnancy, attempting to get pregnant, or actively breast feeding or positive urine pregnancy test (only given to females with child bearing potential). 4. Additional criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemically-confirmed 30-day Continuous Smoking Abstinence | 12 weeks post-TQD (Visit 4) | Number of participants who self report complete smoking abstinence over the last 30 days and are also verified to be abstinent by carbon monoxide (CO) expired breath testing with CO \< 7 parts per million. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phone-assessed Self-reported Abstinence | 52 weeks post-TQD | Number of participants who self reported smoking abstinence over the last 24 hours assessed via single-item question. |
| 7-day Point Prevalence Biochemically Confirmed Abstinence | 12 weeks post-TQD (Visit 4) | Number of participants who self report complete smoking abstinence over the last 7 days and are also verified to be abstinent by carbon monoxide (CO) expired breath testing with CO \< 7 parts per million. |
| Change in Cigarettes Smoked Per Day | 12 weeks post-TQD (Visit 4) | The percentage of participants who decreased the number of daily cigarettes smoked by 50% or more from the baseline assessment visit to 12 weeks post target quit day assessment visit collected by self-report in participants who completed the 12-week post target quit day assessment visit |
| Change in Cigarettes Smoked Per Day (Phone) | 52 weeks post-TQD | The percentage of participants who decreased the number of daily cigarettes smoked by 50% or more from the baseline assessment visit to 52 weeks post target quit day assessment visit collected by self-report in participants who completed the 52-week post target quit day phone assessment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Standard Protocol Participant chooses Varenicline-based treatment and is then randomized to Standard Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts placebo Varenicline. Consistent with Varenicline Standard Treatment, 1 week prior to the TQD the participant will switch to active Varenicline and placebo Bupropion. Participant will continue active Varenicline and placebo Bupropion to 12 weeks post-TQD.
Varenicline Standard Protocol: 4 weeks pre-TQD: Start Placebo Varenicline 1 week prior to TQD: Switch to Active Varenicline
1 week prior to TQD: Start Placebo Bupropion Varenicline + Placebo Bupropion to 12 weeks post TQD | 63 |
| Nicotine Patch Standard Protocol Participant chooses Nicotine patch-based treatment and is then randomized to Standard Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts placebo Nicotine Patch. One week prior to TQD, participant will start placebo Bupropion. Consistent with Nicotine Patch Standard Treatment, participant will start active Nicotine Patch on TQD. Participant will continue active Nicotine Patch and placebo Bupropion to 12 weeks post-TQD.
Nicotine Patch Standard Protocol: 4 weeks pre-TQD: Start Placebo Nicotine Patch TQD: Start active Nicotine Patch
1 week prior to TQD: Start Placebo Bupropion Nicotine Patch + Placebo Bupropion to 12 weeks post TQD | 30 |
| Varenicline Adaptive Protocol Participant chooses Varenicline treatment and is randomized to Adaptive Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts active Varenicline. Two weeks prior to TQD, cigarettes smoked per day is assessed. If the number of cigarettes smoked per day is reduced by \>50%, the participant is considered a Varenicline responder, and starts placebo Bupropion 1 week prior to the TQD. If the participant DOES NOT reduce cigarettes smoked per day by \>50%, the participant is considered a Varenicline non-responder and starts active Bupropion 1 week prior to TQD. Varenicline responders will continue active Varenicline and placebo Bupropion to 12 weeks post TQD. Varenicline non-responders will continue active Varenicline and active Bupropion to 12 weeks post TQD.
Varenicline Adaptive Protocol: VARENICLINE RESPONDER 4 weeks pre-TQD: Start Varenicline 2 weeks pre-TQD: DOES reduce cigs/day by \> 50% 1 week pre-TQD: Start Placebo Bupropion Varenicline + Placebo Bupropion to 12 weeks post TQD
VARENICLINE NON-RESPONDER 4 weeks pre-TQD: Start Varenicline 2 weeks pre-TQD: DOES NOT reduce cigs/day by \> 50%
1 week pre-TQD: Start active Bupropion Varenicline + Bupropion to 12 weeks post TQD | 64 |
| Nicotine Patch Adaptive Protocol Participant chooses Nicotine treatment and is randomized to Adaptive Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts active Nicotine Patches. Two weeks prior to TQD, cigarettes smoked per day is assessed. If cigarettes smoked per day is reduced by \>50%, the participant is considered a Nicotine Patch responder and starts placebo Bupropion 1 week prior to the TQD. If the participant DOES NOT reduce cigarettes smoked per day by \>50%, the participant is considered a Nicotine Patch non-responder and starts active Bupropion 1 week prior to the TQD. Nicotine Patch responders will continue active Nicotine Patches and placebo Bupropion to 12 weeks post TQD. Nicotine Patch non-responders will continue active Nicotine Patches and Bupropion to 12 weeks post TQD.
Nicotine Adaptive Protocol: NICOTINE PATCH RESPONDER 4 weeks pre-TQD: Start Patch 2 weeks pre-TQD: DOES reduce cigs/day by \> 50% 1 week pre-TQD: Start Placebo Bupropion Patch + Placebo Bupropion to 12 weeks post TQD
NICOTINE PATCH NON-RESPONDER 4 weeks pre-TQD: Start Patch 2 weeks pre-TQD: DOES NOT reduce cigs/day by \> 50%
1 week pre-TQD: Start Bupropion Patch + Bupropion to 12 weeks post TQD | 31 |
| Total | 188 |
Baseline characteristics
| Characteristic | Varenicline Standard Protocol | Nicotine Patch Standard Protocol | Varenicline Adaptive Protocol | Nicotine Patch Adaptive Protocol | Total |
|---|---|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 10.5 | 45.0 years STANDARD_DEVIATION 16.3 | 49.1 years STANDARD_DEVIATION 12.6 | 50.3 years STANDARD_DEVIATION 11.6 | 49.1 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 30 Participants | 63 Participants | 29 Participants | 184 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 21 Participants | 19 Participants | 17 Participants | 80 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 6 Participants | 41 Participants | 13 Participants | 98 Participants |
| Sex: Female, Male Female | 30 Participants | 17 Participants | 35 Participants | 19 Participants | 101 Participants |
| Sex: Female, Male Male | 33 Participants | 13 Participants | 29 Participants | 12 Participants | 87 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 | 1 / 63 | 0 / 30 | 0 / 64 | 0 / 31 |
| other Total, other adverse events | 48 / 63 | 25 / 30 | 58 / 64 | 25 / 31 |
| serious Total, serious adverse events | 1 / 63 | 0 / 30 | 1 / 64 | 0 / 31 |
Outcome results
Primary
Biochemically-confirmed 30-day Continuous Smoking Abstinence
Number of participants who self report complete smoking abstinence over the last 30 days and are also verified to be abstinent by carbon monoxide (CO) expired breath testing with CO \< 7 parts per million.
Time frame: 12 weeks post-TQD (Visit 4)
Population: Intent-to-treat analysis of a clinical population with significant comorbidity and minimal exclusion criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Standard Protocol | Biochemically-confirmed 30-day Continuous Smoking Abstinence | 5 Participants |
| Nicotine Patch Standard Protocol | Biochemically-confirmed 30-day Continuous Smoking Abstinence | 3 Participants |
| Varenicline Adaptive Protocol | Biochemically-confirmed 30-day Continuous Smoking Abstinence | 18 Participants |
| Nicotine Patch Adaptive Protocol | Biochemically-confirmed 30-day Continuous Smoking Abstinence | 5 Participants |
Secondary
7-day Point Prevalence Biochemically Confirmed Abstinence
Number of participants who self report complete smoking abstinence over the last 7 days and are also verified to be abstinent by carbon monoxide (CO) expired breath testing with CO \< 7 parts per million.
Time frame: 12 weeks post-TQD (Visit 4)
Population: Intent-to-treat analysis of a clinical population with significant comorbidity and minimal exclusion criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Standard Protocol | 7-day Point Prevalence Biochemically Confirmed Abstinence | 6 Participants |
| Nicotine Patch Standard Protocol | 7-day Point Prevalence Biochemically Confirmed Abstinence | 3 Participants |
| Varenicline Adaptive Protocol | 7-day Point Prevalence Biochemically Confirmed Abstinence | 23 Participants |
| Nicotine Patch Adaptive Protocol | 7-day Point Prevalence Biochemically Confirmed Abstinence | 6 Participants |
Secondary
Change in Cigarettes Smoked Per Day
The percentage of participants who decreased the number of daily cigarettes smoked by 50% or more from the baseline assessment visit to 12 weeks post target quit day assessment visit collected by self-report in participants who completed the 12-week post target quit day assessment visit
Time frame: 12 weeks post-TQD (Visit 4)
Population: Analysis of a clinical population with significant comorbidity and minimal exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline Standard Protocol | Change in Cigarettes Smoked Per Day | 80.4 percentage of participants |
| Nicotine Patch Standard Protocol | Change in Cigarettes Smoked Per Day | 71.4 percentage of participants |
| Varenicline Adaptive Protocol | Change in Cigarettes Smoked Per Day | 89.4 percentage of participants |
| Nicotine Patch Adaptive Protocol | Change in Cigarettes Smoked Per Day | 82.6 percentage of participants |
Secondary
Change in Cigarettes Smoked Per Day (Phone)
The percentage of participants who decreased the number of daily cigarettes smoked by 50% or more from the baseline assessment visit to 52 weeks post target quit day assessment visit collected by self-report in participants who completed the 52-week post target quit day phone assessment.
Time frame: 52 weeks post-TQD
Population: Analysis of a clinical population with significant comorbidity and minimal exclusion criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline Standard Protocol | Change in Cigarettes Smoked Per Day (Phone) | 67.6 percentage of participants |
| Nicotine Patch Standard Protocol | Change in Cigarettes Smoked Per Day (Phone) | 57.1 percentage of participants |
| Varenicline Adaptive Protocol | Change in Cigarettes Smoked Per Day (Phone) | 84.8 percentage of participants |
| Nicotine Patch Adaptive Protocol | Change in Cigarettes Smoked Per Day (Phone) | 62.5 percentage of participants |
Secondary
Phone-assessed Self-reported Abstinence
Number of participants who self reported smoking abstinence over the last 24 hours assessed via single-item question.
Time frame: 52 weeks post-TQD
Population: Intent-to-treat analysis of a clinical population with significant comorbidity and minimal exclusion criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Standard Protocol | Phone-assessed Self-reported Abstinence | 16 Participants |
| Nicotine Patch Standard Protocol | Phone-assessed Self-reported Abstinence | 5 Participants |
| Varenicline Adaptive Protocol | Phone-assessed Self-reported Abstinence | 21 Participants |
| Nicotine Patch Adaptive Protocol | Phone-assessed Self-reported Abstinence | 6 Participants |