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

Tracking Information
First Submitted Date ICMJE	November 19, 2008
First Posted Date ICMJE	November 20, 2008
Last Update Posted Date	March 16, 2016
Study Start Date ICMJE	September 2009
Actual Primary Completion Date	June 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 19, 2008)	Smoking cessation rates [ Time Frame: 24 weeks ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00794573 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 24, 2008)	Smoking abstinence, ≥ 50% reduction in daily consumption of cigarettes, side effects, cumulative side effects, safety [ Time Frame: Smoking abstinence: 52 weeks. Side effects and safety: 4, 12, 24, and 52 weeks. Cumulative side effects: 12 weeks. ]
Original Secondary Outcome Measures ICMJE; (submitted: November 19, 2008)	Smoking abstinence, ≥ 50% reduction in daily consumption of cigarettes, side effects, cumulative side effects, safety. [ Time Frame: Smoking abstinence: 52 weeks. Side effects and safety: 4, 12, 24, and 52 weeks. Cumulative side effects: 12 weeks. ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Evaluation of Varenicline (Champix) in Smoking Cessation for Patients Post-Acute Coronary Syndrome (EVITA) Trial
Official Title ICMJE	Evaluation of Varenicline (Champix) in Smoking Cessation for Patients Post-Acute Coronary Syndrome (EVITA) Trial
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition ICMJE	Acute Coronary Syndrome
Intervention ICMJE	Drug: varenicline 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 Names: Champix (Canada) Chantix (USA); Other: placebo 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.
Study Arms	Experimental: Varenicline 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. Intervention: Drug: varenicline; Placebo Comparator: Sugar pill 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. Intervention: Other: placebo
Publications *	Windle SB, Dehghani P, Roy N, Old W, Grondin FR, Bata I, Iskander A, Lauzon C, Srivastava N, Clarke A, Cassavar D, Dion D, Haught H, Mehta SR, Baril JF, Lambert C, Madan M, Abramson BL, Eisenberg MJ; EVITA Investigators. Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital. CMAJ. 2018 Mar 26;190(12):E347-E354. doi: 10.1503/cmaj.170377.; Dehghani P, Habib B, Windle SB, Roy N, Old W, Grondin FR, Bata I, Iskander A, Lauzon C, Srivastava N, Clarke A, Cassavar D, Dion D, Haught H, Mehta SR, Baril JF, Lambert C, Madan M, Abramson BL, Eisenberg MJ. Smokers and Postcessation Weight Gain After Acute Coronary Syndrome. J Am Heart Assoc. 2017 Apr 18;6(4). pii: e004785. doi: 10.1161/JAHA.116.004785.; Eisenberg MJ, Windle SB, Roy N, Old W, Grondin FR, Bata I, Iskander A, Lauzon C, Srivastava N, Clarke A, Cassavar D, Dion D, Haught H, Mehta SR, Baril JF, Lambert C, Madan M, Abramson BL, Dehghani P; EVITA Investigators. Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome. Circulation. 2016 Jan 5;133(1):21-30. doi: 10.1161/CIRCULATIONAHA.115.019634. Epub 2015 Nov 9.; Windle SB, Bata I, Madan M, Abramson BL, Eisenberg MJ. A randomized controlled trial of the efficacy and safety of varenicline for smoking cessation after acute coronary syndrome: design and methods of the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome trial. Am Heart J. 2015 Oct;170(4):635-640.e1. doi: 10.1016/j.ahj.2015.07.010. Epub 2015 Jul 17.; Grandi SM, Shimony A, Eisenberg MJ. Bupropion for smoking cessation in patients hospitalized with cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials. Can J Cardiol. 2013 Dec;29(12):1704-11. doi: 10.1016/j.cjca.2013.09.014. Review.; Eisenberg MJ, Grandi SM, Gervais A, O'Loughlin J, Paradis G, Rinfret S, Sarrafzadegan N, Sharma S, Lauzon C, Yadav R, Pilote L; ZESCA Investigators. Bupropion for smoking cessation in patients hospitalized with acute myocardial infarction: a randomized, placebo-controlled trial. J Am Coll Cardiol. 2013 Feb 5;61(5):524-32. doi: 10.1016/j.jacc.2012.08.1030.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 14, 2016)	302
Original Estimated Enrollment ICMJE; (submitted: November 19, 2008)	300
Actual Study Completion Date	December 2015
Actual Primary Completion Date	June 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00794573
Other Study ID Numbers ICMJE	EVITA
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Mark Eisenberg, McGill University
Study Sponsor ICMJE	Mark Eisenberg
Collaborators ICMJE	St. Michael's Hospital, Toronto; Sunnybrook Health Sciences Centre; Queen Elizabeth II Health Sciences Centre
Investigators ICMJE	Principal Investigator: Mark J Eisenberg, MD, MPH SMBD - Jewish General Hospital
PRS Account	McGill University
Verification Date	March 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP