Nicotine DependencePhase 3ConNic4NCT01303861
Concurrent Bupropion / Varenicline for Smoking Cessation
A Phase 3 study testing Varenicline, Bupropion and Nicotine patches in people with Nicotine Dependence, run by Duke University at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Varenicline, Bupropion and Nicotine patches
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 702 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2011to Jul 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Duke Center for Nicotine and Smoking Cessation Research
Charlotte, North Carolina, 28210
Duke Center for Nicotine and Smoking Cessation Research
Durham, North Carolina, 27705
Duke Center for Nicotine and Smoking Cessation Research
Raleigh, North Carolina, 27609
Duke Center for Nicotine and Smoking Cessation Research
Winston-Salem, North Carolina, 27103
About this study
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
- Conditions
- Nicotine Dependence
- Being tested
- Varenicline, Bupropion, Nicotine patches, Nicotine Inhaler
- Keywords
- Nicotine addiction, Cigarette smoking, Smoking cessation, Zyban, Chantix, Nicotine patches, Nicotrol Inhaler, varenicline, bupropion
- Medical subject headings
- Tobacco Use Disorder, Cigarette Smoking, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called Chantix
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.
BupropionDrug
Also called Zyban
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.
Nicotine patchesDrug
Also called Nicoderm
Nicotine Replacement Therapy Groups:
- 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
- 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:
- For smokers with high baseline CO: 42 mg/24 h for 1 week
- For smokers with low baseline CO: 21 mg/24 h for 1 week
Nicotine InhalerDrug
Also called Nicotrol Inhaler
Nicotine inhaler to use as needed after quit date
| Study group | Role | What they receive |
|---|---|---|
| varenicline | Active comparator | 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. Receives: Drug: Varenicline |
| Nicotine Patches only | Active comparator | 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. Receives: Drug: Nicotine patches |
| Nicotine Patches with Nicotine Inhaler | Active comparator | 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. Receives: Drug: Nicotine patches; Drug: Nicotine Inhaler |
| varenicline with bupropion | Active comparator | 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. Receives: Drug: Varenicline; Drug: Bupropion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Study week 8 thru week 11
Secondary outcomes (2)
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.
Measured: Six months post quit date
Continuous Cigarette Abstinence From Quit Date
Secondary outcome will include continuous abstinence from quit date to end of treatment (week 11).
Measured: From Quit date to end of treatment (week 11)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionMar 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 702 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Philip Morris USA, Inc.
- Responsible party
- Sponsor
- Investigators
- Jed E Rose, Ph.D., Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01303861
- Sponsor's protocol ID
- Pro00027351
- Other IDs
- 1P50DA027840-01A1
- Acronym
- ConNic4
- Status last verified
- May 2014
- First submitted
- 23 Feb 2011
- Last updated
- 6 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 37142273Hartmann-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.
PubMed 34611902Rose JE, Behm FM. Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. Am J Psychiatry. 2014 Nov 1;171(11):1199-205. doi: 10.1176/appi.ajp.2014.13050595.
PubMed 24934962
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Concurrent Bupropion / Varenicline for Smoking Cessation
- ClinicalTrials.gov ID
- NCT01303861
- Acronym / sponsor ID
- ConNic4 / Pro00027351
- Conditions
- Nicotine Dependence
- Keywords
- Nicotine addiction, Cigarette smoking, Smoking cessation, Zyban, Chantix, Nicotine patches, Nicotrol Inhaler, varenicline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 702 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Philip Morris USA, Inc.
- Study start
- Mar 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 25 Feb 2011 (estimated)
- Results
- Posted 1 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| varenicline | Active comparator | Drug: VareniclineThis 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. |
| Nicotine Patches only | Active comparator | Drug: Nicotine patchesThis 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 with Nicotine Inhaler | Active comparator | Drug: Nicotine patches, Drug: Nicotine InhalerThis 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. |
| varenicline with bupropion | Active comparator | Drug: Varenicline, Drug: BupropionThis 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (34 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VareniclineAlso: ChantixFor 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. | Drug | varenicline, varenicline with bupropion |
| BupropionAlso: ZybanFor 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. | Drug | varenicline with bupropion |
| Nicotine patchesAlso: NicodermNicotine 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 | Drug | Nicotine Patches only, Nicotine Patches with Nicotine Inhaler |
| Nicotine InhalerAlso: Nicotrol InhalerNicotine inhaler to use as needed after quit date | Drug | Nicotine Patches with Nicotine Inhaler |
Primary outcome
Four-week Continuous Abstinence From Cigarette Smoking
Time frame: 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.
2 secondary outcomes
Seven Day Point Abstinence From Cigarette Smoking
Time frame: Six months post quit date
Continuous Cigarette Abstinence From Quit Date
Time frame: From Quit date to end of treatment (week 11)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37142273Livingstone-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.
- Derived from this study: PubMed 34611902Hartmann-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.
- Derived from this study: PubMed 24934962Rose JE, Behm FM. Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. Am J Psychiatry. 2014 Nov 1;171(11):1199-205. doi: 10.1176/appi.ajp.2014.13050595.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jed E Rose, Ph.D. principal investigator
Duke University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Varenicline, Bupropion and Nicotine patches in people with Nicotine Dependence, run by Duke University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Four-week Continuous Abstinence From Cigarette Smoking (time frame: Study week 8 thru week 11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01303861, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2014.