Combination Nicotine Replacement Therapy + Cytisine + Varenicline for Tobacco Use

(Sun Life RCT Trial)

Overseen By Leah Margetson

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: NRT, Cytisine, Varenicline

Disqualifiers: Pregnant, Breastfeeding, Acute mental illness, 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: 1

Duration: 12 weeks

1500 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have used any of the study medications (NRT, cytisine, varenicline) in the past 7 days.

What data supports the effectiveness of the combination drug therapy of Cytisine, Nicotine Replacement Therapy, and Varenicline for tobacco use?

Research shows that combining varenicline with nicotine replacement therapy (NRT) is more effective for quitting smoking than using varenicline alone. This suggests that using a combination of these treatments, including cytisine, could potentially help more people stop smoking. ^{1 2 3 4 5}

Is the combination of Nicotine Replacement Therapy, Cytisine, and Varenicline safe for humans?

Cytisine, varenicline, and nicotine replacement therapy have been used to help people quit smoking, but they can cause side effects. Some people have reported adverse reactions (unwanted effects) with these treatments, but most did not stop using them because of these effects. It's important to monitor for neuropsychiatric (mental health) and cardiovascular (heart-related) risks when using varenicline and nicotine replacement therapy. ^{1 6 7 8 9}

How is the combination of Cytisine, Nicotine Replacement Therapy, and Varenicline unique for smoking cessation?

This treatment is unique because it combines three different approaches: Cytisine, a plant-based compound that targets nicotine receptors; Nicotine Replacement Therapy (NRT), which provides a safer form of nicotine; and Varenicline, a medication that reduces cravings and withdrawal symptoms. This combination aims to enhance smoking cessation success by addressing different aspects of nicotine addiction. ^{1 4 10 11 12}

What is the purpose of this trial?

The purpose of this trial is to test whether clients of Sun Life are willing to join in a quit smoking program that offers counselling and tobacco cessation products to all participants over a 12-month period. The study team will track the safety and usage of 3 types of cessation products as well as the effectiveness of a virtual pharmacy (i.e. cessation products delivered to participants directly from a pharmacy) over a 12-week treatment period. The purpose of this study is to look at 3 approved smoking cessation products used in combination with counselling and virtual delivery of the smoking cessation products. The goal is to track product usage, safety, and adherence (how much of the products people use and how many counselling sessions they complete). Within the study there will also be an observational group who will not receive study medication but who will receive free virtual coaching and follow-up for smoking cessation and complete study questionnaires.

Eligibility Criteria

This trial is for Sun Life clients who smoke and are interested in quitting. Participants will receive counseling and tobacco cessation products over a year, with a focus on the first 12 weeks. The study excludes individuals not meeting specific health criteria or those unable to commit to the program's duration.

Inclusion Criteria

I am 18 or older and a client of Sun Life Assurance Company of Canada.

Able to provide informed consent

Living in Ontario, Canada

Exclusion Criteria

Pregnant or breastfeeding individuals

Actively enrolled in another formal smoking cessation program

Other conditions deemed by the study team to interfere with participation or outcomes in the opinion of the study investigator (for example acutely unwell, life expectancy less than 1 year)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive smoking cessation products and virtual counselling over a 12-week period

12 weeks

Virtual delivery of cessation products and counselling sessions

Follow-up

Participants are monitored for safety, adherence, and smoking cessation status

12 months

Follow-up visits at 1, 3, 6, and 12 months

Treatment Details

Interventions

• Cytisine
• Nicotine Replacement Therapy
• Varenicline

Trial Overview The trial tests three smoking cessation methods: Cytisine, Nicotine Replacement Therapy (patch plus gum/lozenge), and Varenicline (Champix). It evaluates their effectiveness when combined with counseling and direct delivery from a virtual pharmacy over 12 weeks.

Participant Groups

Group I: Varenicline (Champix) Active Control 1 Intervention

Varenicline - standard dose

Group II: Nicotine Replacement Therapy (Nicotine patch plus NRT gum or lozenge) Active Control 1 Intervention

Nicotine replacement therapy patch (titrated based on cigarettes consumed at baseline) plus short term gum or lozenge (as needed)

Group III: Cytisine Active Control 1 Intervention

Cytisine pills, standard dose

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Vita Aid Professional Therapeutics

Collaborator

Trials

1

Recruited

1,500+

Sun Life Assurance Company of Canada

Collaborator

Trials

2

Recruited

1,800+

Lumino Health™ Pharmacy

Collaborator

Trials

1

Recruited

1,500+

Findings from Research

This study will evaluate the effectiveness and safety of combining nicotine salt e-cigarettes with cytisine for smoking cessation in 800 daily smokers over a 12-week period, with a primary focus on achieving biochemically verified abstinence at six months.

The trial aims to provide real-world evidence on this combination therapy's impact, which could inform future smoking cessation practices and policies in New Zealand.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial. Walker, N., Calder, A., Barnes, J., et al.[2023]

Combining varenicline with oral nicotine replacement therapy (NRT) and using smartphone medication reminders led to more days of smoking abstinence compared to using varenicline alone, suggesting that this combination may enhance smoking cessation efforts.

Participants who received smartphone reminders adhered to their varenicline medication more consistently and reported higher usage of NRT, indicating that reminders can improve medication adherence, although combining medications may lead to lower adherence overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial. Sifat, M., Hébert, ET., Ahluwalia, JS., et al.[2023]

Cytisine, a smoking cessation medication used since 1964, has shown a significant increase in the likelihood of successful continuous abstinence from smoking, with a relative risk of 1.74 compared to placebo based on a meta-analysis of eight studies.

The most common adverse reactions associated with cytisine are mild to moderate gastrointestinal symptoms, such as nausea and vomiting, making it a relatively safe option for those looking to quit smoking, especially considering its low cost compared to other cessation medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. Tutka, P., Vinnikov, D., Courtney, RJ., et al.[2020]

In a study of 282,429 adult smokers in the UK, varenicline was linked to an increased risk of self-harm and suicide, but it also showed a reduced risk of all-cause death, suggesting a complex relationship with mental health during smoking cessation.

Nicotine replacement therapy (NRT) was associated with a higher risk of myocardial infarction and self-harm, as well as increased mortality from heart-related issues and chronic obstructive pulmonary disease, indicating potential cardiovascular risks during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink: a case-cross-over study. Thomas, KH., Davies, NM., Taylor, AE., et al.[2022]

Cytisinicline, administered for either 6 or 12 weeks, significantly improved smoking cessation rates compared to placebo, with continuous abstinence rates of 32.6% for the 12-week group versus 7.0% for placebo during weeks 9 to 12.

The treatment was well-tolerated, with only 2.9% of participants discontinuing due to adverse events, and no serious drug-related side effects reported, indicating it is a safe option for aiding smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. Rigotti, NA., Benowitz, NL., Prochaska, J., et al.[2023]

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]

Cytisine and varenicline are two promising partial agonists of nicotinic acetylcholine receptors that can aid in smoking cessation, with cytisine being a low-cost option that has been used for decades but often overlooked in reviews.

Varenicline has shown greater efficacy than existing smoking cessation treatments, supported by encouraging early human trial results, making both drugs potential alternatives for smokers seeking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinic receptor partial agonists as novel compounds for the treatment of smoking cessation. Tutka, P.[2019]

References

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

Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial. [2023]

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

Fifty-two-week continuous abstinence rates of smokers being treated with varenicline versus nicotine replacement therapy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Combining varenicline and nicotine patches: a randomized controlled trial study in smoking cessation. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials. [2023]

5. Canada pubmed.ncbi.nlm.nih.gov

Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial. [2023]

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

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. [2020]

7. Poland pubmed.ncbi.nlm.nih.gov

[Safety of nicotine addiction treatment]. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink: a case-cross-over study. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Cytisine for smoking cessation: a research agenda. [2015]

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

Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. [2023]

11. England 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. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Nicotinic receptor partial agonists as novel compounds for the treatment of smoking cessation. [2019]