Clinical trial NCT04286295: Cytisine Compared to Combination NRT in Relapsed Smokers
Official title: Pilot RCT of Cytisine Compared to Combination Nicotine Replacement Therapy to Reduce Cigarette Consumption in Relapsed Smokers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Smoking Cessation
Coronary Artery Disease
Keywords: Tobacco
Relapse prevention
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2020-02-26
Enrollment: 13
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patient is enrolled in UOHI's Quit Smoking Program;
2. Patient has relapsed to daily smoking ≥10 cigarettes per day within 90 days of discharge from UOHI;
3. Patient is currently smoking ≥10 cigarettes per day.

Exclusion Criteria:

1. Patient has used NRT, cytisine, varenicline, bupropion or a nicotine-containing vaping device within in the past 15 days;
2. Patient is unavailable to come to UOHI for assessments;
3. Patient is unable to provide informed consent;
4. Patient is unable to comprehend the intervention instructions (in the opinion of qualified investigators)

Primary outcomes:
measure: Feasibility of study
timeFrame: Baseline to 25-day follow-up
Secondary outcomes:
measure: Treatment completion
timeFrame: Baseline to 25-day follow-up
measure: Attrition
timeFrame: Baseline to 25-day follow-up
measure: Cigarette consumption
timeFrame: Baseline to 25-day follow-up
measure: Arterial Stiffness
timeFrame: Baseline to 25-day follow-up
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Insitute - Prevention and Wellness Centre
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Andrew Pipe, MD
role: PRINCIPAL_INVESTIGATOR
References: