No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Trial Summary
What is the purpose of this trial?
This project will use the Multiphase Optimization Strategy (MOST) to guide the development of optimized treatment strategies for the two most effective smoking cessation medications (Combination Nicotine Replacement \[C-NRT\] and varenicline). The investigators will recruit daily smokers from primary care to participate in a fully crossed, 2x2x2x2 factorial experiment (N=608) that evaluates 4 different factors: 1) Medication Type (Varenicline vs. C-NRT), 2) Preparation Medication (4 Weeks vs. Standard), 3) Medication Duration (Extended \[24 weeks\] vs. Standard \[12 weeks\]); and 4) Counseling (Intensive vs. Minimal). Participants will complete assessments one week pre-quit and then assessments of smoking status, treatment use, side effects, potential treatment mechanisms (e.g., withdrawal, self-efficacy) during the first week post-target quit date (TQD) and at Weeks 2, 4, 12, 20, 26, and 52 post-target quit date. These data will be used to examine the main and interactive effects of these four factors on various outcomes, with biochemically confirmed 12-month abstinence serving as the primary outcome. These data will also be used to determine which factors and combinations of factors are most effective with regard to 12-month biochemically confirmed abstinence and cost, thereby identifying optimized varenicline and C-NRT treatments, with each developed to yield especially great benefit. These optimized treatments will then be tested in the Optimized Care Project. The investigators will also examine the relative effects of each medication on particular outcomes (e.g., 12-month abstinence).
Will I have to stop taking my current medications?
If you are currently using nicotine replacement therapy (NRT), you will need to switch to the study medication for the duration of the trial. If you are taking bupropion or varenicline, you cannot participate in the trial.
What data supports the effectiveness of the drug Varenicline for smoking cessation?
Research shows that Varenicline is effective for helping people quit smoking, with studies indicating it has similar success rates to combination nicotine replacement therapies. It also outperformed bupropion in a clinical trial, helping reduce withdrawal symptoms and cravings.12345
Is varenicline safe for humans?
Varenicline, used to help people stop smoking, has been linked to some serious mental health side effects like depression and suicidal thoughts. While it can be effective in reducing cravings, it's important to discuss the potential risks with a healthcare provider before starting the medication.56789
How is the drug combination of Nicotine Replacement Therapy and Varenicline unique for smoking cessation?
This treatment is unique because it combines Nicotine Replacement Therapy with Varenicline, a novel drug that acts as a partial agonist on specific brain receptors, helping to reduce cravings and withdrawal symptoms while blocking the rewarding effects of smoking. Varenicline's targeted mechanism of action and its ability to stimulate dopamine release while blocking nicotine receptors make it a promising option compared to other available therapies.210111213
Research Team
ME
Megan E Piper, PhD
Principal Investigator
University of Wisconsin, Madison
Eligibility Criteria
This trial is for daily smokers who've been smoking more than 4 cigarettes a day for the past 6 months, can use study medications safely, and if female and able to have children, must be using birth control. Smokers already on bupropion or varenicline or with recent suicidal thoughts or attempts cannot join.
Inclusion Criteria
If currently using nicotine replacement therapy (NRT), agreeing to use only study medication for the duration of the study
I am using birth control as a woman who can still have children.
Able to read, write, and speak English
See 2 more
Exclusion Criteria
You have had thoughts of harming yourself or attempted to harm yourself in the past.
I am currently taking bupropion or varenicline.
Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Preparation
Participants receive preparation medication and counseling prior to the target quit day (TQD)
4 weeks
1 phone or video counseling session
Treatment
Participants receive either Varenicline or C-NRT with counseling, starting on the target quit day (TQD)
12-24 weeks
Multiple phone or video counseling sessions
Follow-up
Participants are monitored for smoking status, treatment use, and side effects
52 weeks
Assessments at Weeks 2, 4, 12, 20, 26, and 52 post-TQD
Treatment Details
Interventions
Combination Nicotine Replacement Therapy
Intensive Counseling
Minimal Counseling
Varenicline
Trial OverviewThe study tests different strategies to quit smoking using two main treatments: Combination Nicotine Replacement (C-NRT) and varenicline. It looks at medication type, preparation time before quitting, treatment duration, and counseling intensity in various combinations over a year.
Participant Groups
16Treatment groups
Active Control
Group I: 24-week Varenicline with 4-Week Preparation Varenicline and Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 weeks prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 24 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group II: 12-week Varenicline with 4-Week Preparation Varenicline and Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 11 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group III: 24-week Varenicline with 4-Week Preparation Varenicline and Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 weeks prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 24 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group IV: 12-week C-NRT with Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 12 weeks of nicotine patches and nicotine mini-lozenges to use starting on their quit day. Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group V: 24-week C-NRT with Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 24 weeks of nicotine patches and nicotine mini-lozenges, starting on the target quit day (TQD). Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group VI: 12-week Varenicline with Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 11 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group VII: 12-week C-NRT with 4-Week Preparation C-NRT and Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Then, starting on the TQD, participants will receive 12 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke \>10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive a brief 15-30 minute phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group VIII: 12-week C-NRT with 4-Week Preparation C-NRT and Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Starting on the TQD, participants will receive 12 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke \>10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group IX: 24-week C-NRT with 4-Week Preparation C-NRT and Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Starting on the TQD, participants will receive 24 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke \>10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group X: 12-week C-NRT with Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 12 weeks of nicotine patches and nicotine mini-lozenges to use starting on their quit day. Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 8 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 10 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Group XI: 24-week Varenicline with Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 23 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group XII: 24-week C-NRT with 4-Week Preparation C-NRT and Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 14 mg patches starting 4 weeks prior to the target quit day (TQD). Then, starting on the TQD, participants will receive 24 weeks of nicotine patches and nicotine mini-lozenges. Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group XIII: 24-week C-NRT with Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive 24 weeks of nicotine patches and nicotine mini-lozenges, starting on the target quit day (TQD). Participants who smoke more than 10 cigarettes/day will start with a 21 mg patch for 20 weeks, and then titrate down to a 14 mg patch for 2 weeks and then a 7 mg patch for 2 weeks. Participants who smoke 5-10 cigarettes/day will be given 22 weeks of 14 mg patches and then 2 weeks of 7 mg patches. Participants will receive 2 mg mini-lozenges. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group XIV: 12-week Varenicline with Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 11 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group XV: 12-week Varenicline with 4-Week Preparation Varenicline and Minimal CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 4 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily for the next 3 weeks pre-TQD and until 12 weeks post-TQD. Participants randomized to this intervention will receive a brief (15-30 minute) phone or video counseling session 1 week prior to the TQD to promote engagement with free mobile health resources and then a brief (10-20 minute) follow-up phone or video session during the first week post-TQD to mimic a nurse or clinician follow-up after a quit attempt.
Group XVI: 24-week Varenicline with Intensive CounselingActive Control2 Interventions
Participants randomized to this intervention will receive one 0.5 mg pill for the first 3 days, starting 1 week prior to the target quit day (TQD). They will then use one 0.5 mg pill twice daily for the next 4 days. After the first week of study medication ramp up, participants will use one 1 mg pill twice daily until 23 weeks post-TQD. Participants randomized to this intervention will receive four 15-20 minute phone or video counseling sessions (1 prior to the TQD, 1 during the first week post-TQD and during Weeks 2 and 4 post-TQD). The counseling is designed to produce intra-treatment support and skill training, consistent with the Public Health Service (PHS) Clinical Practice Guideline.
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Wisconsin, Madison
Lead Sponsor
Trials
1,249
Recruited
3,255,000+
National Cancer Institute (NCI)
Collaborator
Trials
14,080
Recruited
41,180,000+
Findings from Research
In a study of 3569 smokers, those using varenicline had a significantly higher sustained abstinence rate (15.2%) compared to those using combination nicotine replacement treatment (cNRT) (10.3%) over a 12-month period, indicating that varenicline may be more effective for long-term smoking cessation.
The study highlights that varenicline's effectiveness was observed in a real-world setting, where participants chose their treatment and received structured support, suggesting that it could be a preferred option for smoking cessation programs.
Effectiveness of Varenicline Versus Combination Nicotine Replacement Therapy for Smoking Cessation: One-Year Outcomes in a Smoking Cessation Clinic in Taiwan.Hsueh, KC., Tang, PL., McRobbie, H.[2021]
Varenicline (Champix) is a newly approved medication for smoking cessation that acts as a partial agonist of nicotinic receptors, offering a different mechanism of action compared to traditional therapies like nicotine replacement and bupropion.
Recent studies indicate that varenicline is effective in helping individuals quit smoking and may have advantages over existing treatments, although potential side effects are also discussed.
[Drug of the month. Varenicline (Champix)].Vandemergel, X.[2015]
Participants who chose varenicline (3,116 individuals) for tobacco cessation had higher abstinence rates at both 3 months (22%) and 6 months (17%) compared to those using nicotine replacement therapy (NRT) (13% at 3 months and 11% at 6 months), indicating that varenicline may be more effective in supporting quitting.
The study found that factors such as increasing age, having health insurance, and the number of counseling sessions were associated with higher rates of abstinence, particularly at 3 months, suggesting that these factors could enhance the effectiveness of quitline services.
Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy.Biazzo, LL., Froshaug, DB., Harwell, TS., et al.[2015]
In a study of over 200,000 adults, varenicline (VAR) was found to have lower smoking-attributable and all-cause medical costs compared to nicotine-replacement therapy patches (NRT-P) over a year, suggesting it may be a more cost-effective smoking cessation option.
Among patients who adhered to their treatment, VAR still showed lower annual medical costs despite higher pharmacy costs, indicating that the overall financial burden of smoking cessation may be reduced with VAR compared to NRT-P.
Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice.Lee, LJ., Li, Q., Bruno, M., et al.[2020]
In a randomized controlled trial, varenicline (Chantix) demonstrated a higher abstinence rate from smoking after one year compared to both bupropion SR (Zyban) and a placebo, indicating its efficacy in treating tobacco dependence.
Despite its effectiveness, varenicline has been associated with serious neuropsychiatric side effects, highlighting the importance of discussing potential risks and benefits with patients considering this treatment.
Treatment of nicotine dependence with Chantix (varenicline).Rankin, KV., Jones, DL.[2015]
In a study of 2,682 patients using varenicline for smoking cessation, nausea and vomiting were the most common reasons for discontinuation and the most frequently reported adverse drug reactions, highlighting the need for patient monitoring regarding gastrointestinal side effects.
While some psychiatric events were reported, including anxiety and depression, all cases of suicidal behavior involved patients with prior psychiatric conditions, suggesting that clinicians should closely monitor individuals with such histories when prescribing varenicline.
Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study.Kasliwal, R., Wilton, LV., Shakir, SA.[2021]
In a real-world study involving 566 participants across four European countries, varenicline was found to be an effective smoking cessation aid, with a 64.6% quit rate by the end of the 12-week treatment period.
The safety profile of varenicline was acceptable, with the most common side effects being mild to moderate nausea (8.9%) and insomnia (2.9%), and only 3.4% of participants discontinued due to treatment-related adverse events.
Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study.Boudrez, H., Gratziou, C., Messig, M., et al.[2015]
In a study of 12,159 patients, varenicline was associated with reported neuropsychiatric events, particularly anxiety, but no significant increase in these events was found over time, suggesting that the drug's safety profile remains largely stable.
While 7-17% of neuropsychiatric events were attributed to varenicline by general practitioners, the analysis did not raise significant safety concerns, indicating that further investigation is needed to clarify the relationship between varenicline and anxiety symptoms.
Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England.Buggy, Y., Cornelius, V., Fogg, C., et al.[2021]
Varenicline, a medication used to help people quit smoking, is known to have some psychiatric and behavioral side effects, including reports of tardive dyskinesia, although these were not previously documented in literature.
This study presents the first two documented cases of withdrawal emergent dyskinesias associated with varenicline, highlighting a potential safety concern for users of the medication.
Withdrawal-Emergent Dyskinesias following Varenicline Therapy.Toffey, BA., Rabin, M., Kurlan, R.[2020]
In a phase 2 study involving 411 healthy smokers, varenicline tartrate at doses of 1.0 mg once and twice daily significantly increased quit rates compared to placebo, with 48.0% and 37.3% quitting respectively, versus only 17.1% for placebo.
Varenicline was well tolerated, with discontinuation rates due to adverse events similar to placebo, indicating it is a safe and effective option for smoking cessation, especially at the 1.0 mg twice daily dose for long-term success.
Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.Nides, M., Oncken, C., Gonzales, D., et al.[2022]
In a 24-week study involving 333 participants from China, Singapore, and Thailand, varenicline was found to be significantly more effective than placebo for smoking cessation, with 50.3% of participants achieving 4-week continuous abstinence compared to 31.6% in the placebo group.
Varenicline was safe and well tolerated, showing no significant side effects, which supports its use as a viable option for helping smokers quit.
Effectiveness of Varenicline Versus Combination Nicotine Replacement Therapy for Smoking Cessation: One-Year Outcomes in a Smoking Cessation Clinic in Taiwan. [2021]
Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice. [2020]
Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. [2021]
Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. [2022]