Evaluation of Varenicline (Champix) in Smoking Cessation for Patients Post-Acute Coronary Syndrome (EVITA) Trial

Study Overview
=================
Brief Summary
-----------------
The EVITA study is a clinical trial that will test the effect of varenicline (Champix™), a new drug used to help people quit smoking, in patients who have suffered a heart attack. Varenicline has been recently shown to increase the number of otherwise healthy people who quit smoking compared to placebo (sugar pill). Although varenicline has been shown to reduce smoking in healthy populations, its effectiveness in patients recovering from a heart attack is unknown. The EVITA trial will help answer this question. A total of 300 patients who have recently suffered a heart attack and are active smokers will be recruited in the study. For twelve weeks, half the patients will receive varenicline and the other half will receive placebo pills. Patients will be followed for a period of 12 months. During this time, patients will receive telephone calls and go to clinic visits in order to assess if they are smoking. These follow-ups will also assess any side effects and clinical events such as another heart attack or hospitalization that patients may have had. Smoking cessation will be checked using exhaled carbon monoxide readings and self-reports. The EVITA trial will be the first study to examine the use of varenicline in patients who have recently had a heart attack. These patients, if they continue to smoke, are at high risk of having another cardiac event. If varenicline is shown to be useful in this population, it will have a major impact on prevention of cardiac events in patients who have suffered a heart attack.

Detailed Description
-----------------
Objectives: 1. The primary objective of the Evaluation of Varenicline (Champix™) in SmokIng Cessation for PaTients Post-Acute Coronary Syndrome (EVITA) Trial is to evaluate the impact of varenicline on smoking cessation rates at 24 weeks following an enzyme-positive acute coronary syndrome (ACS). 2. The secondary objectives are to examine the efficacy of varenicline on smoking cessation rates and daily cigarette reduction at 52 weeks, and to determine the safety of varenicline in patients following an ACS. Rationale: Patients who continue smoking after an acute coronary syndrome (ACS) have a 35% increased risk of reinfarction or death compared with those who quit. Many patients attempt to stop smoking after an ACS, but relapse rates approach 66%. A variety of smoking cessation aids have been shown to be effective for the general population. However, physicians are reluctant to use a nicotine-based therapy because of its hemodynamic effects. Varenicline has been recently shown to improve abstinence rates in healthy young smokers compared to bupropion (Zyban™) and placebo. Although varenicline has successfully been shown to reduce smoking rates in healthy young populations, its efficacy in the setting of patients recovering from an ACS is unknown. Methods: The EVITA Trial will directly compare the efficacy of varenicline versus placebo as a means of reducing smoking rates in patients following an ACS. The trial will be a multi-center effort, coordinated from the Jewish General Hospital/McGill University (Montreal, Quebec). A total of 300 patients will be randomized following an ACS but before hospital discharge. While in-hospital, patients will quit smoking and they will be instructed to not restart smoking following discharged. Half the patients will receive varenicline for 12 weeks and the other half will receive placebo pills for 12 weeks. Patients receiving varenicline will be given 1.0 mg twice a day during the 12-week treatment period. Study nurses will perform telephone follow-ups with the patients at weeks 1, 2 and 8, and patients will return for clinic visits at weeks 4, 12, 24, and 52. Smoking abstinence will be assessed at follow-up clinic visits. The primary endpoint will be smoking abstinence at 24 weeks. Smoking abstinence will be defined as complete abstinence in the week prior to the clinic visits and levels of exhaled carbon monoxide ≤ 10 ppm. The secondary endpoints (smoking abstinence at 52 weeks, side effects of varenicline in patients following an ACS, percent of patients attaining a ≥ 50% reduction in daily consumption of cigarettes at 52 weeks, and clinical events following initiation of treatment) will be measured at 1, 2, 4, 8, 12, 24, and 52 weeks. The occurrence of clinical events will be based on the observed frequency of composite events including death, myocardial infarction, and hospitalization for unstable angina. Withdrawal symptoms and number of cigarettes smoked will also be assessed by the use of questionnaires. The EVITA trial will require 36 months for completion: 3 months for preparation, 18 months for patient enrollment, 12 months for follow-up, and 3 months for data analysis and manuscript preparation. Significance: The EVITA trial will be the first to examine the efficacy of varenicline in a group of patients who have suffered an ACS. These patients, if they continue to smoke, are at exceptionally high risk for recurrent cardiac events. If varenicline is effective in this population, it will have a major impact on secondary prevention of recurrent clinical events in patients who suffer an ACS.

Official Title
-----------------
Evaluation of Varenicline (Champix) in Smoking Cessation for Patients Post-Acute Coronary Syndrome (EVITA) Trial

Conditions
-----------------
Acute Coronary Syndrome

Intervention / Treatment
-----------------
* Drug: varenicline
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Active smoker, greater than or equal to 10 cigarettes per day, on average, for the past year. Age greater than or equal to 18 years. Motivated to quit smoking. Able to understand and to provide informed consent in English or French. Likely to be available for follow-up. Suffered an ACS, including myocardial infarction (MI) or unstable angina (UA) with significant coronary artery disease, and currently hospitalized or at discharge from current hospitalization. MI is defined as positive Troponin T, Troponin I, or CK-MB levels and ≥ 1 of the following: Ischemic symptoms (i.e. typical chest pain) for at least 20 minutes. Electrocardiogram (ECG) changes indicative of ischemia (ST-segment elevation or depression). Development of pathological Q waves on the ECG. UA with significant coronary artery disease is defined as all of the following: Negative Troponin T, Troponin I, or CK-MB levels; Ischemic symptoms (i.e. typical chest pain) for at least 20 minutes; ECG changes indicative of ischemia (ST-segment changes); and At least one lesion ≥ 50% on angiogram performed during the current hospitalization. Exclusion Criteria: Medical condition with a prognosis of < 1 year. Pregnant or lactating females. Reported NYHA Class or Killip III or IV at randomization. Previous use of varenicline. Current use of any medical therapy for smoking cessation (e.g. BuSpar, doxepin,fluoxetine, nicotine gum, nicotine patch, or bupropion). History of bulimia or anorexia nervosa. Diagnosis of major depression (requiring medication) in the previous 5 years or diagnosis of two or more lifetime episodes of major depression (requiring medication) A total of 5 or more responses (one of which includes question 1 or 2) of more than half the days or nearly every day to the questions on the PHQ-9 questionnaire. History of suicidal events (previous suicide attempt, suicidal ideation) or family history of suicide. History of or current panic disorder, psychosis, bipolar disease, or dementia. Diagnosed hepatic failure, cirrhosis, hepatitis or history of hepatic impairment (AST or ALT levels greater than or equal to 2 times upper limit of normal prior to admission for ACS). Renal impairment with creatinine levels greater than or equal to 2 times the upper limit of normal. Excessive alcohol consumption defined as greater than or equal to 14 alcoholic drinks per week. Use of any illegal drugs in the past year (e.g. cocaine, heroin, opiates). Use of any marijuana or other tobacco products during the study. Current use of over-the-counter stimulants (e.g. ephedrine, phenylephrine) or anorectics.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline<br>0.5 mg tablet once a day for the first three days, a 0.5 mg tablet twice a day for the following four days, and a 1.0 mg tablet twice a day for the remainder of the 12-week treatment. | Drug: varenicline<br>* 0.5 mg tablet once a day for the first three days, a 0.5 mg tablet twice a day for the following four days, and a 1.0 mg tablet twice a day for the remainder of the 12-week treatment.<br>* Other names: Chantix (USA);|
| Placebo Comparator: Sugar pill<br>placebo for 0.5 mg tablet once a day for the first three days, a 0.5 mg tablet twice a day for the following four days, and a 1.0 mg tablet twice a day for the remainder of the 12-week treatment. | Other: placebo<br>* 0.5 mg tablet once a day for the first three days, a 0.5 mg tablet twice a day for the following four days, and a 1.0 mg tablet twice a day for the remainder of the 12-week treatment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-Day Point Prevalence Smoking Abstinence | 7-day point prevalence abstinence at week 24, defined as self-reported abstinence in the past week and exhaled carbon monoxide ≤10 ppm | 24 weeks | 
| Continuous Smoking Abstinence | Continuous abstinence, defined as self-reported abstinence since baseline and exhaled carbon monoxide ≤10 ppm at all follow-up visits up to and including week 24. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-Day Point Prevalence Smoking Abstinence | 7-day point prevalence abstinence at week 52, defined as self-reported abstinence in the past week and exhaled carbon monoxide ≤10 ppm | 52 weeks | 
| Continuous Smoking Abstinence | Continuous abstinence, defined as self-reported abstinence since baseline and exhaled carbon monoxide ≤10 ppm at all follow-up visits up to and including week 52. | 52 weeks | 
| 7-Day Point Prevalence Smoking Abstinence | 7-day point prevalence abstinence at week 12, defined as self-reported abstinence in the past week and exhaled carbon monoxide ≤10 ppm | 12 weeks | 
| Continuous Smoking Abstinence | Continuous abstinence, defined as self-reported abstinence since baseline and exhaled carbon monoxide ≤10 ppm at all follow-up visits up to and including week 12. | 12 weeks | 
| 7-Day Point Prevalence Smoking Abstinence | 7-day point prevalence abstinence at week 4, defined as self-reported abstinence in the past week and exhaled carbon monoxide ≤10 ppm | 4 weeks | 
| Continuous Smoking Abstinence | Continuous abstinence, defined as self-reported abstinence since baseline and exhaled carbon monoxide ≤10 ppm at all follow-up visits up to and including week 4. | 4 weeks | 
| Reduction in Daily Cigarette Consumption by 50% or Greater |  | 52 weeks | 
| Reduction in Daily Cigarette Consumption by 50% or Greater |  | 24 weeks | 
| Reduction in Daily Cigarette Consumption by 50% or Greater |  | 12 weeks | 
| Reduction in Daily Cigarette Consumption by 50% or Greater |  | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Smoking Cessation, Cardiac Population, Acute Coronary Syndrome, Varenicline, Champix