Smoking Cessation Therapies for Quitting Smoking

Overseen By Jason Robinson, PHD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Opioids, Smoking cessation meds

Disqualifiers: Pregnancy, Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

2010 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase IV trial investigates how to personalize treatments (such as medications and/or counseling) for quitting smoking based on the unique character traits of participants. Nicotine replacement therapy, counseling, and/or drugs such as varenicline and bupropion may help participants quit smoking or change smoking behavior. This trial may also help doctors individualize smoking cessation treatment for participants who do not quit smoking after the first course of treatment.

Do I have to stop taking my current medications to join the trial?

The trial requires you to stop using smoking cessation medications like bupropion, nicotine replacement therapy, or varenicline for at least 7 days before joining. Other medications may be evaluated on a case-by-case basis by the study physician.

What data supports the effectiveness of the drug Bupropion Hydrochloride Controlled-release and other treatments for quitting smoking?

Research shows that nicotine replacement therapy (NRT), bupropion SR, and varenicline are effective first-line therapies for quitting smoking, especially when combined with behavioral support. Varenicline has been found to be more effective than placebo and bupropion SR, and a study comparing varenicline to nicotine patches showed promising results for varenicline. ^{1 2 3 4 5}

Is smoking cessation therapy safe for humans?

Smoking cessation therapies like varenicline, bupropion, and nicotine replacement therapy (NRT) are generally considered safe for most people, including those with cardiovascular disease. However, their safety during pregnancy is less clear, and they should be used cautiously in pregnant women, especially those who are heavy smokers and unable to quit without help. ^{4 6 7 8 9}

How is the drug combination of Bupropion, Nicotine Replacement, and Varenicline unique for smoking cessation?

This combination is unique because it uses three different approaches: Bupropion helps by affecting brain chemicals related to addiction, Nicotine Replacement provides a safer form of nicotine to reduce withdrawal symptoms, and Varenicline partially stimulates nicotine receptors to ease cravings. Together, they may offer a more comprehensive strategy for quitting smoking compared to using each drug alone. ^{3 8 10 11 12}

Research Team

Jason Robinson

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for Texas residents who smoke at least 5 cigarettes a day, want to quit or change their smoking habits, and can be reached by phone. They must agree to telehealth treatment and not use other nicotine products during the study. Pregnant women, those with serious medical/psychiatric issues, or using certain medications are excluded.

Inclusion Criteria

Have an address and telephone number where they may be reached

Able to follow verbal and written instructions in English and complete all aspects of the study

Be the only participant in their household currently receiving treatment on this protocol

Exclusion Criteria

Current substance use disorder (Drug Abuse Screening Test [DAST] score > 3; Alcohol Use Disorders Identification Test [USAUDIT] score > 24)

You are experiencing very strong feelings of sadness or depression, or have thoughts of hurting yourself.

I have used smoking cessation medications in the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage I

Participants receive varenicline or NRT with counseling for 6 weeks. Those who quit smoking continue treatment for an additional 6 weeks.

6-12 weeks

Weekly visits (in-person or virtual)

Treatment Stage II

Participants who do not quit smoking are randomized to different treatment groups for an additional 6 weeks.

6 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months

Follow-up visits at 3 and 6 months

Treatment Details

Interventions

• Bupropion Hydrochloride Controlled-release
• Nicotine Replacement
• Tobacco Cessation Counseling
• Varenicline

Trial Overview The PISCES I Trial is testing personalized treatments for quitting smoking in cancer patients. It includes nicotine replacement therapy, counseling, and medications like varenicline and bupropion. The goal is to find out which combination of these methods works best based on individual characteristics.

Participant Groups

Group I: Group VII (varenicline and NRT, counseling) Experimental Treatment 4 Interventions

Participants receive varenicline as in Group I and NRT as in Group II for 6 weeks. Participants also receive behavioral smoking cessation counseling.

Group II: Group VI (varenicline or NRT, bupropion, counseling) Experimental Treatment 5 Interventions

Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive bupropion PO daily for 6 weeks and behavioral smoking cessation counseling.

Group III: Group V (higher dose varenicline or NRT, counseling) Experimental Treatment 4 Interventions

Participants receive a higher dose and continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.

Group IV: Group IV (varenicline or NRT, counseling) Experimental Treatment 4 Interventions

Participants switch to a different therapy and receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.

Group V: Group III (varenicline or NRT, counseling) Experimental Treatment 4 Interventions

Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 additional weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.

Group VI: Group II (NRT, counseling) Experimental Treatment 3 Interventions

Participants receive NRT consisting of a patch, lozenges, or gum daily for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling.

Group VII: Group I (varenicline, counseling) Experimental Treatment 3 Interventions

Participants receive varenicline PO daily or BID for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling.

Bupropion Hydrochloride Controlled-release is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Zyban for:

• Smoking cessation

Approved in Canada as Wellbutrin XL for:

• Major depressive disorder
• Seasonal affective disorder

Approved in Japan as Bupropion for:

• Depression

Approved in Switzerland as Wellbutrin SR for:

• Major depressive disorder

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A consensus among 37 international experts led to the development of decision rules for prescribing smoking cessation pharmacotherapy, emphasizing the importance of patient preferences and experiences alongside evidence-based practices.

The guidelines suggest specific combinations of therapies, such as using two forms of nicotine replacement therapy (NRT) or combining bupropion with NRT, particularly for patients with high dependence or those who have not succeeded with monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An algorithm for tailoring pharmacotherapy for smoking cessation: results from a Delphi panel of international experts. Bader, P., McDonald, P., Selby, P.[2023]

In a 52-week study involving 746 participants, varenicline was found to be significantly more effective than transdermal nicotine replacement therapy (NRT) for smoking cessation, with a continuous abstinence rate of 55.9% compared to 43.2% for NRT during the last 4 weeks of treatment.

Varenicline also led to significantly lower levels of craving, withdrawal symptoms, and smoking satisfaction compared to NRT, although it had a higher incidence of nausea as a side effect (37.2% for varenicline vs. 9.7% for NRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Aubin, HJ., Bobak, A., Britton, JR., et al.[2022]

In a study of 11,968 participants in Taiwan, varenicline was found to be more effective than nicotine replacement therapy (NRT) patch in achieving smoking abstinence, with higher odds ratios for 7-day, 1-month, and 6-month point-prevalence rates.

Varenicline showed significant benefits for both women and smokers with light to moderate nicotine dependence, indicating its effectiveness across different demographics and levels of nicotine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan. Chang, PY., Lo, PC., Chang, HC., et al.[2018]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

A study involving 406 smokers evaluated the effectiveness of extended treatment with sustained-release bupropion and cognitive-behavioral therapy (CBT) over 40 weeks, showing that all extended treatments were more effective than standard treatment.

CBT, when combined with treatment, significantly improved long-term smoking abstinence rates at weeks 64 and 104, suggesting that brief provider contact and CBT can enhance long-term success in quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using extended cognitive behavioral treatment and medication to treat dependent smokers. Hall, SM., Humfleet, GL., Muñoz, RF., et al.[2021]

In a study of over 1 million deliveries in Australia, varenicline exposure during pregnancy was associated with a lower risk of adverse perinatal events compared to unexposed women, suggesting it may be a safer option than previously thought.

Varenicline-exposed infants had lower rates of prematurity, being small for gestational age, and severe neonatal complications compared to those exposed to nicotine replacement therapy (NRT), challenging the current preference for NRT over varenicline in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study. Tran, DT., Preen, DB., Einarsdottir, K., et al.[2020]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. Vandemergel, X.[2015]

Nicotine replacement therapy (NRT) significantly doubles quit rates for smoking cessation, especially when combined with behavioral therapy, and includes effective options like gum, patches, inhalers, and sprays.

NRT is generally safe for most patients with cardiovascular disease, but its use during pregnancy should be limited to heavy smokers who cannot quit, highlighting the need for careful consideration of patient safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nicotine preparations and other preparations for smoking cessation]. Tonstad, S.[2015]

In a study involving 294 participants, varenicline was found to be significantly more effective than placebo for smoking cessation, with lasting effects observed up to 6 months after treatment.

Varenicline not only helped with quitting smoking but also reduced symptoms of depression and negative emotions, without increasing the risk of neuropsychiatric adverse events, making it a safe option for those looking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. Cinciripini, PM., Robinson, JD., Karam-Hage, M., et al.[2022]

Nicotine replacement therapy (NRT) is recommended as the first-line treatment for smoking cessation due to its well-documented efficacy and mild side effects, with a 1-year quit rate of about 20-25% when combined with counseling.

Varenicline is slightly more effective than bupropion SR for quitting smoking, but both are suitable options for individuals who have not succeeded with NRT, especially considering the potential side effects associated with bupropion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which drug to be used in smoking cessation? Tønnesen, P.[2017]

In a study of 38,954 individuals in the UK, 64.3% of first-time smokers attempting to quit were prescribed nicotine replacement therapy (NRT) patches, with the 21 mg/24 hours patch being the most common option.

The use of combination NRT therapies increased significantly from 25.7% in 2008 to 44.8% in 2011, indicating a trend towards more comprehensive smoking cessation support, but the majority of patients still primarily received patch monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General practitioner prescribing of single and combination nicotine replacement therapy in the UK: a retrospective database study. Johnson, M., Anderson, P., Lockhart, I.[2021]

Combination treatments, particularly varenicline with nicotine patches, can lead to higher smoking abstinence rates compared to using varenicline alone, especially in heavy smokers who are more dependent on tobacco.

Overall, combined medications were well tolerated, making them a viable option for hard-core smokers who have struggled to quit with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combinations of pharmacological treatments in smoking cessation. A systematic review]. Underner, M., Perriot, J., Peiffer, G., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

An algorithm for tailoring pharmacotherapy for smoking cessation: results from a Delphi panel of international experts. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

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]

5. United States pubmed.ncbi.nlm.nih.gov

Using extended cognitive behavioral treatment and medication to treat dependent smokers. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study. [2020]

7. Belgium pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. [2015]

8. Norway pubmed.ncbi.nlm.nih.gov

[Nicotine preparations and other preparations for smoking cessation]. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. [2022]

10. Poland pubmed.ncbi.nlm.nih.gov

Which drug to be used in smoking cessation? [2017]

11. England pubmed.ncbi.nlm.nih.gov

General practitioner prescribing of single and combination nicotine replacement therapy in the UK: a retrospective database study. [2021]

12. France pubmed.ncbi.nlm.nih.gov

[Combinations of pharmacological treatments in smoking cessation. A systematic review]. [2021]