Smoking CessationCYTvsNRT+NCT04286295
Cytisine Compared to Combination NRT in Relapsed Smokers
A study testing Cytisine, Nicoderm C-Q Transdermal Product and Nicorette Lozenge Product in people with Smoking Cessation and Coronary Artery Disease, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
Trial summary
Cigarette smoking causes cardiovascular disease (CVD) yet many smokers with CVD are unable to quit despite strong desire to do so. Within 90 days of discharge, about 30% of smokers have returned to daily smoking and almost 60% have relapsed by 1 year. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Smoking Cessation, Coronary Artery Disease
- What is being tested?
- Cytisine, Nicoderm C-Q Transdermal Product and Nicorette Lozenge Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- 14 Mar 2022to 7 Nov 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient is enrolled in UOHI's Quit Smoking Program;
- Patient has relapsed to daily smoking ≥10 cigarettes per day within 90 days of discharge from UOHI;
- Patient is currently smoking ≥10 cigarettes per day.
Who cannot join
- Patient has used NRT, cytisine, varenicline, bupropion or a nicotine-containing vaping device within in the past 15 days;
- Patient is unavailable to come to UOHI for assessments;
- Patient is unable to provide informed consent;
- Patient is unable to comprehend the intervention instructions (in the opinion of qualified investigators)
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of Ottawa Heart Insitute - Prevention and Wellness Centre
Ottawa, Ontario, K1Y 4W7
About this study
Official title: Pilot RCT of Cytisine Compared to Combination Nicotine Replacement Therapy to Reduce Cigarette Consumption in Relapsed Smokers
Cigarette smoking causes cardiovascular disease (CVD) yet many smokers with CVD are unable to quit despite strong desire to do so. Within 90 days of discharge, about 30% of smokers have returned to daily smoking and almost 60% have relapsed by 1 year. Patients with CVD who resume smoking are more likely to experience new events (e.g. heart attack or stroke) or die. New approaches are required. A new type of cessation product is a plant-based medication called Cytisine. Cytisine is taken orally over 25 days and reduces the pleasurable sensations that smokers get from cigarettes and reduces withdrawal symptoms. The primary research question is whether or not it is feasible to conduct a large-scale trial of the effectiveness of this product compared to conventional nicotine replacement therapy in smokers who have failed to quit using conventional methods. To determine feasibility, a pilot study will be conducted of sixty smokers (30 men, 30 women) with CVD who have been treated for smoking cessation but have relapsed within 90 days of discharge. Participants will complete a baseline assessment and will be randomly assigned to either the combination nicotine replacement therapy group (patch plus lozenge) or cytisine group. Participants will be treated for 25 days and then will return to UOHI so adherence to treatment and smoking status can be assessed. Feasibility of the larger trial will be based on: the recruitment rates; adherence to assigned treatments; dropout rates; and differences in 25-day quit rates between groups.
Read the detailed description
Cigarette smoking is a causative factor in the development of coronary heart disease (CHD), and is the most dangerous form of tobacco use. Effective treatments for smoking cessation exist but relapse to cigarette smoking is common, principally due to nicotine addiction and related symptoms of withdrawal. Little is known about how best to support smokers who have relapsed in subsequent attempts to change their smoking behavior. One emerging treatment has features that might make it appealing to smokers and may be effective in the setting of recent relapse: cytisine.
Cytisine is a plant-based smoking cessation medication with more than 50 years of use in central/eastern Europe. Cytisine is a partial agonist of nicotinic acetylcholine receptors (nAChRs), which is central to the effect of nicotine on the reward pathway. Cytisine acts by reducing the rewarding effect of nicotine and attenuating nicotine withdrawal symptoms. A recent review concluded that cytisine is the most promising future smoking cessation treatment. Cytisine is inexpensive to produce and is currently priced much lower than other cessation medications. It is well-tolerated by smokers and requires a shorter treatment period (i.e. 25 days) than conventional treatments. Because it is plant-based, cytisine may be attractive for smokers who prefer 'natural' medicines. Numerous placebo-controlled studies have demonstrated the safety and efficacy of cytisine. One high-quality pragmatic non-inferiority trial (n = 1310) found that cytisine was superior to nicotine replacement therapy (NRT) in improving self-reported continuous abstinence rates at 1 week, and 1, 2 and 6 months when both groups received minimal behavioural support. In Canada, cytisine is marketed as the natural health product Cravv™.
The long-term goal is to conduct a definitive, large-scale randomized controlled trial (RCT) of the efficacy of cytisine compared to conventional treatment (i.e. combination NRT) for smoking cessation among smokers who have relapsed to smoking following hospitalization for a CHD-related event. Prior to conducting a larger, definitive RCT there is a need to conduct a pilot study to better understand the potential feasibility of such a trial.
- Conditions
- Smoking Cessation, Coronary Artery Disease
- Being tested
- Cytisine, Nicoderm C-Q Transdermal Product, Nicorette Lozenge Product
- Keywords
- Tobacco, Relapse prevention
- Medical subject headings
- Smoking Cessation, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytisineDrug
Cytisine is a plant-based smoking cessation medication. Cytisine acts by reducing the rewarding effect of nicotine and attenuating nicotine withdrawal symptoms. A recent review concluded that cytisine is the most promising future smoking cessation treatment. Cytisine is inexpensive to produce and is currently priced much lower than other cessation medications. It is well-tolerated by smokers and requires a shorter treatment period than conventional treatments. Because it is plant-based, cytisine may be attractive for smokers who prefer 'natural' medicines. Numerous placebo-controlled studies have demonstrated the safety and efficacy of cytisine. One high-quality pragmatic non-inferiority trial (n = 1310) found that cytisine was superior to nicotine replacement therapy (NRT) in improving self-reported continuous abstinence rates at 1 week, and 1, 2 and 6 months when both groups received minimal behavioural support.
Nicoderm C-Q Transdermal ProductDrug
Also called NRT+
The Nicoderm® patch plus Nicorette® Lozenge will be provided to participants in the combination NRT group. Participants will be instructed to apply a new patch each day. They will continue to wear patches for 25 days.
Nicorette Lozenge ProductDrug
Participants in the NRT group will receive Nicorette Lozenges to use during their 25-day quit attempt. They will receive enough lozenges to last for the 25-day treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Cytisine | Experimental | Cravv™ (Zpharm, Waterloo) is a natural health product licensed by Health Canada to assist with smoking cessation; each oral capsule contains 1.5mg of cytisine. The dosing is as follows: 6 capsules daily for the first 3 days; 5 capsules daily for days 4-12; 4 capsules daily for days 13-16; 3 capsules daily for days 17-20; and 1-2 capsules daily for days 21-25. Receives: Drug: Cytisine |
| NRT+ | Active comparator | The Nicoderm® patch plus Nicorette® Lozenge will be provided to participants in the combination NRT group. Participants smoking less than 15 cigarettes per day will be provided with 14 mg patches while those smoking 15 or more cigarettes per day will receive 21 mg patches. Participants will be told to apply a new patch each morning. Participants will be instructed to use the lozenges as needed (up to 15 per day) to overcome nicotine cravings. Lozenges are available in both 2mg and 4mg strengths. For those who are smoking less than 15 cigarettes per day, they will be given the 2mg strength. For those who are smoking 15 or more cigarettes per day, they will receive the 4mg strength. Receives: Drug: Nicoderm C-Q Transdermal Product; Drug: Nicorette Lozenge Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of study
will be feasible to recruit 10 relapsed smokers with CHD per month to a study of cytisine vs. combination NRT
Measured: Baseline to 25-day follow-up
Secondary outcomes (4)
Treatment completion
Participants will complete at least 70% of their prescribed treatment
Measured: Baseline to 25-day follow-up
Attrition
There will be less than 5% attrition over a 25-d treatment period
Measured: Baseline to 25-day follow-up
Cigarette consumption
Cigarette consumption will drop by 5 cigs/d more in the cytisine group compared to the combination NRT group by the end of the 25-d treatment period
Measured: Baseline to 25-day follow-up
Arterial Stiffness
Arterial stiffness, as measured by pulse wave velocity, will improve in smokers who are able to achieve complete abstinence (i.e. smoking zero cigarettes per day).
Measured: Baseline to 25-day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study start14 Mar 2022
- Primary completion7 Nov 2023
- Study completion7 Nov 2023
Why it stopped: Feasibility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Pipe, MD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04286295
- Sponsor's protocol ID
- 20190720-01H
- Acronym
- CYTvsNRT+
- Status last verified
- Dec 2023
- First submitted
- 21 Feb 2020
- Last updated
- 8 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This is a pilot study so datasets will not be shared until a written request is submitted to the PI.
Publications
Mir H, Mullen KA, Heshmati J, Baldwin A, Quirouette E, Serano E, Coja M, Pipe AL, Reid RD. Cytisine Use Vs Nicotine Replacement Therapy in Relapsed Smokers with Heart Disease: Feasibility Results from a Pilot Randomized Trial. CJC Open. 2025 May 16;7(8):1062-1069. doi: 10.1016/j.cjco.2025.05.005. eCollection 2025 Aug.
PubMed 40894854Mir H, Heshmati J, Mullen KA, Baldwin A, Quirouette E, Pipe A, Reid R. Cytisine compared to combination nicotine replacement therapy to reduce cigarette consumption in relapsed smokers: protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2025 Jan 28;11(1):10. doi: 10.1186/s40814-024-01591-4.
PubMed 39876021
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot RCT of Cytisine Compared to Combination Nicotine Replacement Therapy to Reduce Cigarette Consumption in Relapsed Smokers
- ClinicalTrials.gov ID
- NCT04286295
- Acronym / sponsor ID
- CYTvsNRT+ / 20190720-01H
- Conditions
- Smoking Cessation, Coronary Artery Disease
- Keywords
- Tobacco, Relapse prevention
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Feasibility
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- 14 Mar 2022 (actual)
- Primary completion
- 7 Nov 2023 (actual)
- Study completion
- 7 Nov 2023 (actual)
- First posted
- 26 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cigarette smoking causes cardiovascular disease (CVD) yet many smokers with CVD are unable to quit despite strong desire to do so. Within 90 days of discharge, about 30% of smokers have returned to daily smoking and almost 60% have relapsed by 1 year. Patients with CVD who resume smoking are more likely to experience new events (e.g. heart attack or stroke) or die. New approaches are required. A new type of cessation product is a plant-based medication called Cytisine. Cytisine is taken orally over 25 days and reduces the pleasurable sensations that smokers get from cigarettes and reduces withdrawal symptoms. The primary research question is whether or not it is feasible to conduct a large-scale trial of the effectiveness of this product compared to conventional nicotine replacement therapy in smokers who have failed to quit using conventional methods. To determine feasibility, a pilot study will be conducted of sixty smokers (30 men, 30 women) with CVD who have been treated for smoking cessation but have relapsed within 90 days of discharge. Participants will complete a baseline assessment and will be randomly assigned to either the combination nicotine replacement therapy group (patch plus lozenge) or cytisine group. Participants will be treated for 25 days and then will return to UOHI so adherence to treatment and smoking status can be assessed. Feasibility of the larger trial will be based on: the recruitment rates; adherence to assigned treatments; dropout rates; and differences in 25-day quit rates between groups.
Detailed description
Cigarette smoking is a causative factor in the development of coronary heart disease (CHD), and is the most dangerous form of tobacco use. Effective treatments for smoking cessation exist but relapse to cigarette smoking is common, principally due to nicotine addiction and related symptoms of withdrawal. Little is known about how best to support smokers who have relapsed in subsequent attempts to change their smoking behavior. One emerging treatment has features that might make it appealing to smokers and may be effective in the setting of recent relapse: cytisine.
Cytisine is a plant-based smoking cessation medication with more than 50 years of use in central/eastern Europe. Cytisine is a partial agonist of nicotinic acetylcholine receptors (nAChRs), which is central to the effect of nicotine on the reward pathway. Cytisine acts by reducing the rewarding effect of nicotine and attenuating nicotine withdrawal symptoms. A recent review concluded that cytisine is the most promising future smoking cessation treatment. Cytisine is inexpensive to produce and is currently priced much lower than other cessation medications. It is well-tolerated by smokers and requires a shorter treatment period (i.e. 25 days) than conventional treatments. Because it is plant-based, cytisine may be attractive for smokers who prefer 'natural' medicines. Numerous placebo-controlled studies have demonstrated the safety and efficacy of cytisine. One high-quality pragmatic non-inferiority trial (n = 1310) found that cytisine was superior to nicotine replacement therapy (NRT) in improving self-reported continuous abstinence rates at 1 week, and 1, 2 and 6 months when both groups received minimal behavioural support. In Canada, cytisine is marketed as the natural health product Cravv™.
The long-term goal is to conduct a definitive, large-scale randomized controlled trial (RCT) of the efficacy of cytisine compared to conventional treatment (i.e. combination NRT) for smoking cessation among smokers who have relapsed to smoking following hospitalization for a CHD-related event. Prior to conducting a larger, definitive RCT there is a need to conduct a pilot study to better understand the potential feasibility of such a trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cytisine | Experimental | Drug: CytisineCravv™ (Zpharm, Waterloo) is a natural health product licensed by Health Canada to assist with smoking cessation; each oral capsule contains 1.5mg of cytisine. The dosing is as follows: 6 capsules daily for the first 3 days; 5 capsules daily for days 4-12; 4 capsules daily for days 13-16; 3 capsules daily for days 17-20; and 1-2 capsules daily for days 21-25. |
| NRT+ | Active comparator | Drug: Nicoderm C-Q Transdermal Product, Drug: Nicorette Lozenge ProductThe Nicoderm® patch plus Nicorette® Lozenge will be provided to participants in the combination NRT group. Participants smoking less than 15 cigarettes per day will be provided with 14 mg patches while those smoking 15 or more cigarettes per day will receive 21 mg patches. Participants will be told to apply a new patch each morning. Participants will be instructed to use the lozenges as needed (up to 15 per day) to overcome nicotine cravings. Lozenges are available in both 2mg and 4mg strengths. For those who are smoking less than 15 cigarettes per day, they will be given the 2mg strength. For those who are smoking 15 or more cigarettes per day, they will receive the 4mg strength. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patient is enrolled in UOHI's Quit Smoking Program;
- Patient has relapsed to daily smoking ≥10 cigarettes per day within 90 days of discharge from UOHI;
- Patient is currently smoking ≥10 cigarettes per day.
Key exclusion criteria (4 listed)
- Patient has used NRT, cytisine, varenicline, bupropion or a nicotine-containing vaping device within in the past 15 days;
- Patient is unavailable to come to UOHI for assessments;
- Patient is unable to provide informed consent;
- Patient is unable to comprehend the intervention instructions (in the opinion of qualified investigators)
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 |
|---|---|---|
| CytisineCytisine is a plant-based smoking cessation medication. Cytisine acts by reducing the rewarding effect of nicotine and attenuating nicotine withdrawal symptoms. A recent review concluded that cytisine is the most promising future smoking cessation treatment. Cytisine is inexpensive to produce and is currently priced much lower than other cessation medications. It is well-tolerated by smokers and requires a shorter treatment period than conventional treatments. Because it is plant-based, cytisine may be attractive for smokers who prefer 'natural' medicines. Numerous placebo-controlled studies have demonstrated the safety and efficacy of cytisine. One high-quality pragmatic non-inferiority trial (n = 1310) found that cytisine was superior to nicotine replacement therapy (NRT) in improving self-reported continuous abstinence rates at 1 week, and 1, 2 and 6 months when both groups received minimal behavioural support. | Drug | Cytisine |
| Nicoderm C-Q Transdermal ProductAlso: NRT+The Nicoderm® patch plus Nicorette® Lozenge will be provided to participants in the combination NRT group. Participants will be instructed to apply a new patch each day. They will continue to wear patches for 25 days. | Drug | NRT+ |
| Nicorette Lozenge ProductParticipants in the NRT group will receive Nicorette Lozenges to use during their 25-day quit attempt. They will receive enough lozenges to last for the 25-day treatment period. | Drug | NRT+ |
Primary outcome
Feasibility of study
Time frame: Baseline to 25-day follow-up
will be feasible to recruit 10 relapsed smokers with CHD per month to a study of cytisine vs. combination NRT
4 secondary outcomes
Treatment completion
Time frame: Baseline to 25-day follow-up
Attrition
Time frame: Baseline to 25-day follow-up
Cigarette consumption
Time frame: Baseline to 25-day follow-up
Arterial Stiffness
Time frame: Baseline to 25-day follow-up
Results and safety
The study was stopped early (reason given: Feasibility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2023.
- Derived from this study: PubMed 40894854Mir H, Mullen KA, Heshmati J, Baldwin A, Quirouette E, Serano E, Coja M, Pipe AL, Reid RD. Cytisine Use Vs Nicotine Replacement Therapy in Relapsed Smokers with Heart Disease: Feasibility Results from a Pilot Randomized Trial. CJC Open. 2025 May 16;7(8):1062-1069. doi: 10.1016/j.cjco.2025.05.005. eCollection 2025 Aug.
- Derived from this study: PubMed 39876021Mir H, Heshmati J, Mullen KA, Baldwin A, Quirouette E, Pipe A, Reid R. Cytisine compared to combination nicotine replacement therapy to reduce cigarette consumption in relapsed smokers: protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2025 Jan 28;11(1):10. doi: 10.1186/s40814-024-01591-4.
- Individual participant dataSharing planned: No. This is a pilot study so datasets will not be shared until a written request is submitted to the PI.
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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.
Andrew Pipe, MD principal investigator
Ottawa Heart Institute Research Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cytisine, Nicoderm C-Q Transdermal Product and Nicorette Lozenge Product in people with Smoking Cessation and Coronary Artery Disease, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
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 3 inclusion and 4 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: stopped early, as of the sponsor's last update on 8 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
Are results available for this study?
The study was stopped early (reason given: Feasibility). Results are not available in the source record.
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?
Feasibility of study (time frame: Baseline to 25-day follow-up). 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 NCT04286295, which also lists 2 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 8 Dec 2023; AzTrials last refreshed its copy on 31 Oct 2026.