PeRiopEratiVE smokiNg cessaTion Trial

Study Overview
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Brief Summary
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PREVENT is a multicentre, 2x2 factorial, randomized clinical trial that aims to determine the effect of cytisine versus placebo, as well as the effect of video messaging to support smoking cessation versus standard of care in perioperative patients. This trial aims to investigate the effects of cytisine and text messaging on 6-month continuous abstinence rates. PREVENT will also assess secondary outcomes at 30 days, 56 days and 6 months post-randomization: 7-day point prevalence abstinence, urge to smoke, time to first lapse, time to relapse, number of cigarettes smoking if still smoking, pulmonary complications, vascular complications, wound and infectious complications, stroke, time in hospital and acute hospital care.

Official Title
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PeRiopEratiVE smokiNg cessaTion Trial

Conditions
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Smoking (Tobacco) Addiction, Smoking Cessation

Intervention / Treatment
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* Drug: Cytisine
* Behavioral: Video Messaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: are ≥18 years of age are scheduled to undergo surgery within 1-28 days are a current smoker (i.e., smoked at least 10 cigarettes per day during the previous year and had no period of smoking abstinence longer than 6 months) and not currently using any smoking cessation treatment and, have a smart mobile phone with an active, up to date data plan and with internet access provide informed consent to participate. Exclusion Criteria: are pregnant or breastfeeding or expecting to become pregnant during the study follow-up period are deemed unreliable for study procedures or follow-up have a documented allergic reaction to cytisine, or its components (non-medicinal ingredients) or to the non-medicinal ingredients of the placebo. had myocardial infarction, unstable angina, or stroke/transient ischemic attack within the preceding 2 weeks. will have surgery with expected nil intake by mouth for 2 or more days have previously participated in PREVENT have a known diagnosis of untreated pheochromocytoma; Schizophrenia/bipolar psychiatric illness and currently psychotic; currently having suicidal ideation or risk of suicide as determined by the site physician, known history of moderate to severe depression; currently uncontrolled severe hypertension (≥180/120 mmHg) despite treatment; known history of uncontrolled hyperthyroidism (thyrotoxicosis), severe renal impairment i.e., creatinine clearance of less than 30 ml per minute (Cockcroft- Gault equation) or receiving long-term dialysis, or known diagnosis of severe liver disease as determined by the site physician or documented in the clinical history.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: 2x2 factorial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cytisine and Video Messaging<br>Administration of cytisine (pharmaceutical support) to patients on a set dose schedule with behavioural support through video messaging. | Drug: Cytisine<br>* Listed as a natural health product in Canada, cytisine is utilized to aid in smoking cessation<br>Behavioral: Video Messaging<br>* Supportive messaging utilizing a video messaging platform to encourage patients to abstain from smoking throughout the treatment period.<br>|
| Placebo Comparator: Placebo and Video Messaging<br>Administration of placebo (inactive drug) to patients on a set dose schedule with behavioural support through video messaging. | Behavioral: Video Messaging<br>* Supportive messaging utilizing a video messaging platform to encourage patients to abstain from smoking throughout the treatment period.<br>|
| Active Comparator: Cytisine and No Video Messaging<br>Administration of cytisine (pharmaceutical support) to patients on a set dose schedule with behavioural support according to standard care such as a phone number for a self-help line. | Drug: Cytisine<br>* Listed as a natural health product in Canada, cytisine is utilized to aid in smoking cessation<br>|
| No Intervention: Placebo and No Video Messaging<br>Administration of placebo (inactive drug) to patients on a set dose schedule behavioural support according to standard care such as a phone number for a self-help line. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Cessation | complete abstinence (smoking not more than 5 cigarettes) beginning on day 5 post randomization and lasting until the assessment at 6 months post-randomization with biochemical verification for those who report abstinence, using exhaled breath carbon monoxide (cut-off <10 parts per million [ppm]) measured with a carbon monoxide (CO) monitor | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day point-prevalence abstinence at 30 days | Self-report of not smoking cigarettes [not even a puff] in the 7 days before the 30-day follow-up | 30 days | 
| 7-day point-prevalence abstinence at 56 days | Self-report of not smoking cigarettes [not even a puff] in the 7 days before the 56-day follow-up | 56-days | 
| 7-day point-prevalence abstinence at 6-months | Self-report of not smoking cigarettes [not even a puff] in the 7 days before the 6-month follow-up | 6-months | 
| Urge to smoke | urge to smoke using the Mood and Physical Symptoms Scale [MPSS] at baseline and 6 months; a higher score indicates a stronger urge to smoke; To assess the effect of abstinence calculate the change from baseline (just prior to stopping smoking) to the post-abstinence follow-up point for items 1 to 7 and 10 to 12, and take the raw scores for items 8 and 9 | baseline and 6-months | 
| Number of cigarettes smoked daily if still smoking | Number of cigarettes smoked daily if still smoking | 30 days, 56 days and 6 months | 
| Time to first lapse | Time to first cigarette smoked after the initial quit, even a single puff | 6 months | 
| Time to first relapse | Time to return to smoking > 5 cigarettes/day for three or more concurrent days from quit date | 6 months | 
| 6 month continuous abstinence rate | Complete abstinence (smoking not more than 5 cigarettes) beginning on the quit date and lasting until the assessment at 6 months post-randomization with biochemical verification for those who report abstinence, using exhaled breath carbon monoxide (cut-off <10 ppm) measured with a carbon monoxide (CO) monitor. *Cigarettes smoked within 5 days of randomization will be discounted. | 6-months | 
| Wound complications | Seroma- wound drainage or repeated dressings required; Wound dehiscence or delayed wound healing | 6 months | 
| Infectious complications | Infection - defined as a pathologic process caused by the invasion of normally sterile tissue, fluid, or body cavity by pathogenic or potentially pathogenic organisms. Surgical site infection- An infection that occurs within 30 days after surgery and involves the skin, subcutaneous tissue of the incision (superficial incisional), or the deep soft tissue (e.g., fascia, muscle) of the incision (deep incisional). Sepsis- Based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Sepsis requires a quick Sequential Organ Failure Assessment (qSOFA) Score ≥2 points due to infection. The qSOFA includes the following items and scoring system: 1. altered mental status (1 point); 2. systolic blood pressure ≤100 mm Hg (1 point); and 3. respiratory rate ≥22 breaths per minute (1 point). | 6 months | 
| Respiratory complications | Pneumonia - defined as an acute infection of the pulmonary parenchyma that is associated with at least one sign or symptom of lower respiratory acute infection (e.g., cough, pleuritic chest pain) or acute systemic illness (e.g., fever, chills, confusion, hypoxemia); accompanied by the presence of an acute infiltrate/consolidation on a chest radiograph or auscultatory findings consistent with pneumonia (such as crackles and/or localized rales) for which there is no other explanation. Respiratory insufficiency requiring ventilatory support - Patient intubated or put on bilevel positive airway pressure (BiPAP). | 6 months | 
| Non-fatal Myocardial infarction | according to the 4th universal definition | 6 months | 
| Number of Patients with Proximal venous thrombo-embolism | The diagnosis of PE requires any one of the following: A high probability ventilation/perfusion lung scan, An intraluminal filling defect of a segmental or larger artery on a helical computerized tomography (CT) scan, An intraluminal filling defect on pulmonary angiography, or A positive diagnostic test for deep venous thrombosis A. Non-diagnostic ventilation/perfusion lung scan B. Non-diagnostic helical CT scan. The diagnosis of proximal DVT (leg or arm) requires: Thrombosis involving the popliteal vein or more proximal veins for leg DVT and axillary or more proximal veins for arm DVT, AND Evidence of vein thrombosis by any one of the following: 1. A persistent intraluminal filling defect on contrast venography, 2. Non-compressibility of one or more venous segments on B mode compression ultrasonography, or 3. A clearly defined intraluminal filling defect on contrast enhanced computed tomography. | 6 months | 
| Stroke | Stroke is defined as either: 1. a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting ≥24 hours or leading to death; or 2. a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting <24 hours with positive neuroimaging consistent with a stroke. | 6 months | 
| Non-fatal cardiac arrest | Nonfatal cardiac arrest is defined as successful resuscitation from either documented or presumed ventricular fibrillation, sustained ventricular tachycardia, asystole, or pulseless electrical activity requiring cardiopulmonary resuscitation, pharmacological therapy, or cardiac defibrillation. | 6 months | 
| Death | The definition of death is all cause mortality. | 6 months | 
| Length of hospital stay | Defined as time of hospital admission to time of discharge from hospital after index surgery. | time of hospital admission to time of discharge for surgical stay | 
| Acute hospital care since discharge | Acute-hospital care is a composite outcome of hospital re-admission (patient admission to an acute-care hospital) and emergency department visit (patient visit to an emergency department, which includes urgent-care centre visit). | after hospital discharge for the study surgery to 6-month follow-up |