Varenicline + NRT for Smoking Cessation

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Smoking cessation meds, MAOIs, Opioids

Disqualifiers: Uncontrolled hypertension, Severe kidney disease, Serious disease, Psychiatric disorders, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of varenicline to nicotine replacement therapy (NRT), such as patches and lozenges, in helping people quit smoking. Varenicline mimics nicotine's effects in the brain without causing addiction. Participants will receive either varenicline or NRT and attend regular counseling sessions to support their quitting journey. The trial seeks individuals who smoke at least five cigarettes or similar products daily and are interested in quitting. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand how it benefits more patients.

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

The trial requires you to stop using certain smoking cessation medications like Wellbutrin, Bupropion, Zyban, nicotine replacement therapy, and Chantix at least 7 days before joining. If you are taking certain depression medications like MAOIs or Elavil, you need to stop 14 days before. Other medications will be evaluated on a case-by-case basis by the study physician.

What is the safety track record for these treatments?

Research has shown that varenicline is generally well-tolerated and aids in smoking cessation. Studies indicate that individuals using varenicline are more likely to quit smoking than those taking a placebo, which contains no active medicine. Some users experienced side effects, with nausea being the most common, but it was typically milder than with other treatments.

Reports have noted that some varenicline users required psychiatric care, occurring at a similar rate to those using nicotine patches or gum. This suggests that varenicline is about as safe as other common smoking cessation methods. Overall, varenicline appears effective without causing serious problems for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining varenicline with nicotine replacement therapy (NRT) for smoking cessation because it offers a potentially more effective way to quit smoking than using either method alone. Varenicline works by targeting nicotine receptors in the brain, reducing cravings and withdrawal symptoms, which is different from traditional NRT that mainly provides a small amount of nicotine to ease withdrawal. By combining varenicline with NRT, this approach could enhance the overall success rate of quitting, providing a dual-action strategy that addresses both the chemical and behavioral aspects of nicotine addiction. This combination may offer smokers a more comprehensive support system to overcome their addiction and increase their chances of long-term cessation.

What evidence suggests that this trial's treatments could be effective for smoking cessation?

Research shows that varenicline, which participants in this trial may receive, is a strong choice for quitting smoking. Studies have found it to be the most effective single medication for this purpose. In this trial, one group will receive varenicline, while another group will receive a combination of nicotine patches and lozenges. Extending varenicline use to 24 weeks instead of 12 can reduce the chance of relapse and increase the success of quitting. Overall, varenicline helps many people quit smoking for good compared to not using any medication. ^{2 6 7 8 9}

Who Is on the Research Team?

Jason Robinson

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adult cigarette smokers who smoke at least 5 cigarettes a day, are interested in quitting, and can follow instructions in English. They must not use other tobacco products frequently or be on certain medications like smoking cessation drugs or some antidepressants. People with severe kidney or liver disease, uncontrolled high blood pressure, recent heart issues, or unstable psychiatric conditions cannot join.

Inclusion Criteria

You have an address and telephone number where he/she may be reached.

Smoking 5 or more cigarettes, little cigars and/or cigarillos per day, on average, within the 2 months preceding the screening visit and expired carbon monoxide (CO) greater than or equal to 6 parts per million (ppm) (if less than or equal to 5, then positive cotinine test)

Interested in treatment that might change smoking behavior

Exclusion Criteria

I have severe kidney or liver disease.

Any medical or psychiatric condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, as determined by the principal investigator and/or study physician

I have not had a serious or unstable illness in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either varenicline or nicotine replacement therapy for smoking cessation, with behavioral counseling over 12 weeks

12 weeks

4 in-person visits, 4 phone visits, 4 brief supportive phone calls

Re-randomization and Additional Treatment

Participants who fail to achieve abstinence at week 6 are re-randomized to receive 6 additional weeks of therapy, either continuing the same treatment, switching to the other treatment, or receiving a high-dose version

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Follow-up at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Lozenge
• Nicotine Patch
• Varenicline

Trial Overview The study compares the effectiveness of varenicline (a non-addictive nicotine-like drug) to nicotine replacement therapy (patches and lozenges) combined with counseling to help people quit smoking. It's a randomized pilot phase IV trial where participants are randomly assigned to either treatment without knowing which one they're getting.

How Is the Trial Designed?

Group I: Group I (varenicline and placebo) Experimental Treatment 3 Interventions

Patients receive varenicline PO QD or BID, placebo patches QD, and placebo lozenges PO QD beginning on day 9 and continue for 6 weeks. Patients that are abstinent at week 6 may continue treatment for an additional 6 weeks. Patients also receive behavioral smoking cessation counseling consisting of 4 in-person visits, 4 phone visits, and 4 brief supportive phone calls lasting 10-15 minutes each over the 12 weeks of treatment.

Group II: Group II (placebo, nicotine patch and lozenge) Placebo Group 4 Interventions

Patients receive placebo tablets PO QD or BID, nicotine patches QD, and nicotine lozenges PO QD beginning on day 9 and continue for 6 weeks. Patients that are abstinent at week 6 may continue treatment for an additional 6 weeks. Patients also receive behavioral smoking cessation counseling consisting of 4 in-person visits, 4 phone visits, and 4 brief supportive phone calls lasting 10-15 minutes each over the 12 weeks of treatment.

Varenicline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation
• Dry eye disease

Approved in European Union as Champix for:

• Smoking cessation

Approved in Canada as Champix for:

• Smoking cessation

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+

Published Research Related to This Trial

Vinorelbine tartrate is an FDA-approved treatment for advanced, unresectable non-small cell lung cancer, known for its favorable safety profile and the ability to be administered weekly in an outpatient setting.

While approximately 40% of patients experience severe granulocytopenia, this side effect is quickly reversible, and only about 8% of patients need hospitalization for related complications, indicating that it can be managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate: a promising new chemotherapeutic agent. Baldwin, PD.[2018]

Vinorelbine tartrate is an effective treatment for non-small cell lung cancer (NSCLC) and has a low reported prevalence of respiratory adverse effects, typically under 5%.

However, there is a potential risk of increased pulmonary toxicity in patients with diffuse pulmonary NSCLC, as demonstrated by a case of acute respiratory failure following vinorelbine infusion in a patient with a hypercoagulable state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory failure following vinorelbine tartrate infusion in a patient with non-small cell lung cancer. Kouroukis, C., Hings, I.[2019]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 is a highly effective medication for smoking cessation, showing superior efficacy compared to placebo and bupropion in clinical trials involving chronic smokers, and it helps alleviate withdrawal symptoms.

The recommended treatment regimen involves starting varenicline one week before the quit date, with a titration schedule to minimize side effects like nausea, making it a suitable option for smokers who struggle with other cessation aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. Lam, S., Patel, PN.[2017]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). Rankin, KV., Jones, DL.[2015]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Smoking cessation is crucial for health, and psychiatric nurses should actively support patients in using therapies like varenicline (Chantix) to quit smoking.

Recent research has raised safety concerns about varenicline, including its potential links to neuropsychiatric side effects, seizures, and interactions with alcohol, which clinicians need to consider when recommending this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. Tobin, TJ., Tobin, ML.[2018]

In a study of 148 outpatients, varenicline showed increasing smoking cessation rates with longer treatment durations, achieving an 84.6% abstinence rate in those treated for 9 to 12 weeks.

Patients experiencing adverse events had varying abstinence rates, with the highest success in those receiving active nosotropic medication, suggesting that maintaining regular dosage for 12 weeks can enhance treatment efficacy even in patients with side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sustainable efficacy of oral varenicline for smoking cessation]. Onizawa, S., Taniguchi, H., Nozu, T., et al.[2015]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4824380/

Varenicline for smoking cessation: a narrative review of ... Extending the use of varenicline from 12 to 24 weeks reduces relapse and improves smoking cessation outcomes.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2820435

Varenicline and Nicotine Replacement Therapy for ... Varenicline is the most effective sole pharmacotherapy for smoking cessation and is as effective as combination nicotine replacement therapy ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9293179/

Comparative clinical effectiveness and safety of tobacco ... Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2817927

Enhanced vs Standard Varenicline Treatment for Tobacco ... Varenicline treatment for aiding smoking cessation has been shown to be effective for diverse populations of smokers and has been used with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871622004094

Varenicline and related interventions on smoking cessation Both interventions were effective in promoting abstinence and reducing tobacco use over time. Combining CBT with CM for smoking cessation did ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2962400/

Varenicline for smoking cessation: efficacy, safety, and ... After 52 weeks of follow-up, subjects receiving varenicline had significantly higher smoking abstinence rates compared with those receiving placebo (44% versus ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2793375

Efficacy and Safety of Varenicline for Smoking Cessation in ... Throughout the trial, patients in the varenicline group were at least 3 times more likely to quit smoking compared with patients in the placebo ...

8. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-chantix-varenicline-and-risk-neuropsychiatric

Safety review update of Chantix (varenicline) and risk ... In the DoD study's propensity score matched samples, there were 18 psychiatric hospitalizations among Chantix users and 16 among NRT users. A ...

9. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2818356

Smoking Cessation After Initial Treatment Failure With ... On average, varenicline and combined nicotine replacement therapy (CNRT) appear to consistently produce the highest levels of long-term ...