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| ID | Type | Description | Link |
|---|---|---|---|
| 09-002459 | Other Identifier | Mayo Clinic IRB number | |
| 1R01CA138417 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| University of Minnesota | OTHER |
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This study provides an opportunity to combine varenicline and bupropion SR and capitalize on the potential additive benefit. The investigators hypothesize that this will further increase long-term (≥ 6 months) smoking abstinence rates.
Cigarette smoking is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States and accounts for 30% of U.S. cancer deaths. Varenicline and bupropion SR (sustained-release) are non nicotine pharmacotherapies FDA-indicated for the treatment of tobacco dependence in cigarette smokers. Although varenicline has proven greater efficacy than bupropion SR, both medications are associated with high end-of-treatment smoking abstinence rates. However, almost two-thirds of smokers treated with varenicline report smoking at 6 months. Because varenicline and bupropion SR have different mechanisms of action and different neuropharmacologic targets, combination pharmacotherapy with these agents may increase long-term smoking abstinence rates above what is observed with single-agent therapy. In our recent pilot study of combination therapy with varenicline and bupropion SR, we observed treatment to be well-tolerated with 7-day point prevalence smoking abstinence rates of 71% (95% CI: 54-85%) at 3 months and 58% (95% CI: 41-74%) at 6 months. Determining the efficacy of combination therapy compared to single-agent therapy has immediate and important clinical implications. In this study, we will conduct a randomized, multicenter, controlled clinical trial evaluating the efficacy of combination therapy with varenicline and bupropion SR compared to varenicline and placebo in 506 cigarette smokers at the Mayo Clinic in Rochester, MN, and the University of Minnesota in Minneapolis, MN.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| varenicline and buproprion SR | Active Comparator | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. |
|
| varenicline and placebo | Placebo Comparator | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Varenicline | Drug | varenicline - 1 mg bid for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Prolonged Smoking Abstinence Rates at 12 Weeks in Cigarettes Smokers. | Prolonged smoking abstinence is defined as no smoking, not even a puff, in the last 7 days, and a negative response to the question "Since 2 weeks after your target quit date, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks?" | 3 months |
| Point Prevalence Abstinence at 3 Months. | biochemically confirmed 7-day point prevalence abstinence defined as no smoking, not even a puff, in the previous 7 days. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Prolonged Smoking Abstinence Rates at 26 Weeks in Cigarettes Smokers. | 6 months | |
| Weight Gain From Baseline to 3 Months | Weight change from baseline to three months in those who met criteria for prolonged abstinence at the 3 month visit |
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Inclusion Criteria:
3) Subject is able to complete all study visits 4) Subject is in good health as determined by the investigator 5) Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments 6) Subject is motivated to stop smoking.
Exclusion Criteria:
Female and were pregnant, lactating or likely to become pregnant during the trial and not able nor willing to use contraception or had:
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| Name | Affiliation | Role |
|---|---|---|
| Jon Ebbet, MD | Mayo Clinic | Principal Investigator |
| Dorothy Hatsukami, PhD | University of Minnesota | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Of Minnesota | Minneapolis | Minnesota | 55414 | United States | ||
| Mayo Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24399554 | Result | Ebbert JO, Hatsukami DK, Croghan IT, Schroeder DR, Allen SS, Hays JT, Hurt RD. Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA. 2014 Jan 8;311(2):155-63. doi: 10.1001/jama.2013.283185. | |
| 37142273 | Derived | Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8. |
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Study subjects who consented, were screened for entry criteria, and asked to return for a physical exam and medical history. If eligible and still interested, the volunteer was asked to return to the baseline visit at which time they would receive the study medication assignment.
Recruitment was between October 2009 and April 2012. Volunteers from local communities of Rochester, MN, Minneapolis, MN and LaCrosse, WI, were recruited using newspaper classified ads, radio, TV, internet ads, print ads in magazines, word of mouth, and volunteer wait lists.
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| ID | Title | Description |
|---|---|---|
| FG000 | Varenicline and Buproprion SR | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and bupropion: varenicline - 1 mg bid for 12 weeks bupropion sr - 150 mg bid for 12 weeks |
| FG001 | Varenicline and Placebo | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and placebo: varenicline (1 mg bid) for 12 weeks placebo for 12 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Smokers from the local community who smoked 10 cigarettes or more per day for the 6 months prior to study entry.
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| ID | Title | Description |
|---|---|---|
| BG000 | Varenicline and Buproprion SR | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and bupropion: varenicline - 1 mg bid for 12 weeks bupropion sr - 150 mg bid for 12 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Prolonged Smoking Abstinence Rates at 12 Weeks in Cigarettes Smokers. | Prolonged smoking abstinence is defined as no smoking, not even a puff, in the last 7 days, and a negative response to the question "Since 2 weeks after your target quit date, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks?" | intention-to-treat (all randomized subjects included) | Posted | Number | participants | 3 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Varenicline and Buproprion SR | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and bupropion: varenicline - 1 mg bid for 12 weeks bupropion sr - 150 mg bid for 12 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| trauma | Injury, poisoning and procedural complications | Non-systematic Assessment | sustained trauma during a motor vehicle collision |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| sleep disturbance | General disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jon Ebbert | Mayo Clinic | 507-284-4736 | ebbert.jon@mayo.edu |
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| ID | Term |
|---|---|
| D012907 | Smoking |
| ID | Term |
|---|---|
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000068580 | Varenicline |
| D000073893 | Sugars |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| placebo | Drug | placebo for 12 weeks |
|
|
| bupropion SR | Drug | bupropion sr - 150 mg bid for 12 weeks |
|
|
| 3 months |
| Point Prevalence Abstinence at 6 Months. | Biochemically confirmed abstinence as no smoking, even a puff, for the prior 7 days. | 6 months |
| Prolonged Abstinence at 12 Months | 12 months |
| Point Prevalence Abstinence at 12 Months | Biochemically confirmed abstinence defined as no smoking, not even a puff, in the last 7 days | 12 months |
| Rochester |
| Minnesota |
| 55905 |
| United States |
| Franciscan Skemp Hospital | La Crosse | Wisconsin | 54601 | United States |
| 34611902 | Derived | Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4. |
| Adverse Event |
|
| Physician Decision |
|
| BG001 | Varenicline and Placebo | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and placebo: varenicline (1 mg bid) for 12 weeks placebo for 12 weeks |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| smoking rate | Mean | Standard Deviation | cigarettes per day |
|
| OG001 | Varenicline and Placebo | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and placebo: varenicline (1 mg bid) for 12 weeks placebo for 12 weeks |
|
|
|
| Secondary | Prolonged Smoking Abstinence Rates at 26 Weeks in Cigarettes Smokers. | intention to treat - all subjects | Posted | Number | participants | 6 months |
|
|
|
|
| Secondary | Weight Gain From Baseline to 3 Months | Weight change from baseline to three months in those who met criteria for prolonged abstinence at the 3 month visit | analysis was restricted to subjects who had weight measured at the 3 month visit and were classified as meeting criteria for prolonged abstinence | Posted | Mean | Standard Deviation | kilograms | 3 months |
|
|
|
|
| Primary | Point Prevalence Abstinence at 3 Months. | biochemically confirmed 7-day point prevalence abstinence defined as no smoking, not even a puff, in the previous 7 days. | intent to treat - all subjects | Posted | Number | participants | 3 months |
|
|
|
|
| Secondary | Point Prevalence Abstinence at 6 Months. | Biochemically confirmed abstinence as no smoking, even a puff, for the prior 7 days. | Intention to treat - all subjects | Posted | Number | participants | 6 months |
|
|
|
|
| Secondary | Prolonged Abstinence at 12 Months | intention to treat - all subjects | Posted | Number | participants | 12 months |
|
|
|
|
| Secondary | Point Prevalence Abstinence at 12 Months | Biochemically confirmed abstinence defined as no smoking, not even a puff, in the last 7 days | Posted | Number | participants | 12 months |
|
|
|
|
| 6 |
| 249 |
| 165 |
| 249 |
| EG001 | Varenicline and Placebo | Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year. varenicline and placebo: varenicline (1 mg bid) for 12 weeks placebo for 12 weeks | 6 | 257 | 161 | 257 |
|
| food poisining | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| diverticulitis | Gastrointestinal disorders | Non-systematic Assessment |
|
| breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| acute coronary syndrome | Cardiac disorders | Non-systematic Assessment |
|
| deep vein thrombosis | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| coronary artery disease | Cardiac disorders | Non-systematic Assessment | new diagnosis |
|
| pneumothorax | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| death | Immune system disorders | death due to complications from human immunodeficiency virus 6 months after the study drug was discontinued |
|
| attempted suicide | Psychiatric disorders | Non-systematic Assessment | 9 months after the study drug was discontinued |
|
| lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| nausea | Gastrointestinal disorders |
|
| constipation | Gastrointestinal disorders |
|
| headache | Nervous system disorders |
|
| irritability | General disorders |
|
| anxiety | General disorders |
|
| difficulty concentrating | General disorders |
|
| mood disturbance | General disorders |
|
| dizziness | General disorders |
|
| abnormal dreams | General disorders |
|
| restlessness | General disorders |
|
| depressive symptoms | Psychiatric disorders |
|
| fatigue | General disorders |
|
| dry mouth | General disorders |
|
| dispepsia | Gastrointestinal disorders |
|
| flatulance | Gastrointestinal disorders |
|
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| D011810 | Quinoxalines |
| D002241 | Carbohydrates |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |