Cytisine Compared to Combination NRT in Relapsed Smokers

NCT04286295 | Terminated DMC

• 1 other identifier: 20190720-01H
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Smoking Cessation; Coronary Artery Disease

Keywords

Tobacco; Relapse prevention

Outcome Measures

Primary Outcomes (1)

• Feasibility of study

  will be feasible to recruit 10 relapsed smokers with CHD per month to a study of cytisine vs. combination NRT

  Baseline to 25-day follow-up

Secondary Outcomes (4)

• Treatment completion

  Baseline to 25-day follow-up

• Attrition

  Baseline to 25-day follow-up

• Cigarette consumption

  Baseline to 25-day follow-up

• Arterial Stiffness

  Baseline to 25-day follow-up

Study Arms (2)

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.

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.

Drug: Nicoderm C-Q Transdermal Product; Drug: Nicorette Lozenge Product

Interventions

Cytisine DRUG

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.

Cytisine

Nicoderm C-Q Transdermal Product DRUG

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.

Also known as: NRT+

NRT+

Nicorette Lozenge Product DRUG

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.

NRT+

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (1)

University of Ottawa Heart Insitute - Prevention and Wellness Centre

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (2)

• 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.

  PMID: 40894854 DERIVED

• Mir 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.

  PMID: 39876021 DERIVED

MeSH Terms

Conditions

Smoking Cessation; Coronary Artery Disease

Interventions

cytisine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Andrew Pipe, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 26, 2020
• Study Start: March 14, 2022
• Primary Completion: November 7, 2023
• Study Completion: November 7, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)