Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome: The ZESCA Trial

Myocardial Infarction Clinical Trial

— ZESCA  

Official title:

Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome: The ZESCA Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00689611
• Other study ID #: ZESCA 9197
• Secondary ID: ISRCTN75356261
• Status: Completed
• Phase: Phase 3
• First received: May 30, 2008
• Last updated: April 10, 2015
• Start date: December 2005
• Est. completion date: June 2010

Study information

• Verified date: April 2015
• Source: McGill University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Patients who continue to smoke after a heart attack have a 35% increased risk of a recurrent event or death compared with those who quit. Many patients attempt to stop smoking after a heart attack, but relapse rates approach 66%. A variety of smoking cessation aids have been shown to be effective for the general population. However, bupropion is the only non-nicotine replacement therapy shown to improve abstinence rates in healthy young smokers. Furthermore, nicotine replacement therapies (NRTs) are contraindicated in the immediate period following a heart attack because of the undesirable effects of nicotine. Although bupropion has been successfully used to reduce smoking rates in healthy young populations, its efficacy and safety in the setting of patients recovering from an ACS is unknown. These patients, if they continue to smoke, are at exceptionally high risk for recurrent cardiac events. If bupropion is effective in this population, it will have a major impact on secondary prevention of recurrent clinical events in patients who suffer a heart attack.

Description:

Patients who continue smoking after ACS have a 35% increased risk of reinfarction or death compared with those who quit. Many patients attempt to stop smoking after an acute coronary syndrome (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. Bupropion is the only non-nicotine replacement therapy shown to improve abstinence rates in healthy young smokers by approximately 50%. Although bupropion has successfully been used to reduce smoking rates in healthy young populations, its efficacy and safety in the setting of patients recovering from an ACS is unknown.

The ZESCA Trial will directly compare the efficacy and safety of bupropion versus placebo as a means of reducing smoking rates in patients following an ACS. The ZESCA Trial will be a multi-center effort, coordinated from the Jewish General Hospital/McGill University (Montreal, Quebec). A total of 1500 patients will be randomized following an ACS but before hospital discharge via an Internet web site. Prior to the start of the treatment, patients in both treatment arms will receive a standard physician-administered counseling session regarding smoking cessation. Patients will begin treatment in-hospital and will be monitored in-hospital for ≥ 2 days prior to discharge. Half the patients will receive bupropion for 9 weeks and the other half will receive placebo pills for 9 weeks. Patients receiving bupropion will take 150 mg once per day for 3 days and then 150 mg twice per day for the remainder of 9 weeks. Prior to discharge, the patients will receive an information sheet listing the possible side effects of bupropion. They will be advised to consult the treating physician should they experience any listed side effects. While in-hospital, patients will have quit smoking and they will be instructed to not restart smoking when discharged. Phone calls to the patients will be made by the study nurses at weeks 1 and 2 of the 9-week treatment period. In addition, the patients will have clinic visits at weeks 4 and 9 as well as months 6 and 12. Smoking abstinence will be assessed at 4 weeks, 9 weeks, 6 months, and 12 months after randomization. Smoking abstinence will be defined as the complete abstinence in the week prior to the clinic visits and levels of exhaled carbon monoxide ≤ 10 ppm. Side effects of bupropion in patients following ACS as well as clinical events following initiation of treatment will be measured at weeks 1-8 (by telephone calls), and weeks 4 and 9 as well as months 6 and 12 (by clinic visits). Withdrawal symptoms will also be assessed by the nurses during their weekly calls.

Trials previously conducted with bupropion involved young healthy smokers. The ZESCA trial will be the first to examine the utility of bupropion in a group of patients with an ACS. These patients, if they continue to smoke, are at exceptionally high risk for recurrent cardiac events. If bupropion is effective in this population, it will have a major impact on secondary prevention of recurrent clinical events in patients who suffer an ACS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = 18 years of age

• Smoke at least 10 cigarettes/day for the past year

• Suffered an enzyme-positive ACS

• Planned hospitalization of =24 hours

• Motivated to quit smoking

• Likely to be available for follow-up

• Able to understand and read English or French

Exclusion Criteria:

• Medical condition with a prognosis of < 1 year

• Pregnant or lactating

• Current use of Wellbutrin or any other medications that contain bupropion

• Current use of any medical therapy for smoking cessation (e.g. BuSpar, fluoxetine, doxepin, nicotine gum, or nicotine patch)

• Current seizure disorder, history of seizures or predisposition to seizures (e.g. history of brain tumor, severe head trauma, or stroke)

• History of bulimia or anorexia nervosa

• Current diagnosis of major depression (requiring medication), bipolar disease, or dementia

• History of suicidal events (previous suicide attempt, suicidal ideation) or family history of suicide

• Diagnosed hepatic failure, cirrhosis, hepatitis or history of hepatic impairment (AST or ALT levels = 2 times upper limit of normal prior to admission for ACS)

• Renal impairment with creatinine levels = 2 times the upper limit of normal

• Excessive alcohol consumption defined as = 14 alcoholic drinks per week

• Use of any illegal drugs in the past year (e.g. cocaine, heroin, opiates)

• Current use of medications that lower seizure threshold e.g. amantadine, anti-depressants, anti-malarials, anti-psychotics, levodopa, lithium, quinolone antibiotics, ritonavir, systemic steroids, theophyllin, type 1C antiarrhythmics (e.g. encainide, flecainide, propafenone)

• Use of MAO inhibitors or thioridazine in the past 15 days

• Current use of over-the-counter stimulants (e.g. ephedrine, phenylephrine) or anoretics

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Infarction
• Myocardial Infarction
• Smoking
• Syndrome

Intervention

Drug:
• Bupropion HCl ER
150 mg tablets po qd for 3 days and then 150 mg po bid for remainder of 9 weeks
• Placebo
Placebo

Locations

Country	Name	City	State
Bangladesh	National Heart Foundation of Bangladesh	Dhaka
Canada	Peter Lougheed Centre of the Calgary General Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Valley Regional Hospital	Kentville	Nova Scotia
Canada	Hopital de la Cite de la Sante	Laval	Quebec
Canada	CHA Hotel-Dieu de Levis	Levis	Quebec
Canada	Hopital Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Hotel-Dieu	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	SMBD- Jewish General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital, General Campus	Ottawa	Ontario
Canada	Hopital Laval	Quebec
Canada	New Brunswick Heart Centre	Saint Johns	New Brunswick
Canada	Saskatchewan Drug Research Institute	Saskatoon	Saskatchewan
Canada	Hopital Fleurimont	Sherbrooke	Quebec
Canada	CSSS de Sorel-Tracy	Sorel	Quebec
Canada	CSSS de la Region de Thetford	Thetford Mines	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Vancouver Coastal Health	Vancouver	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Canada	Victoria General Hospital	Winnipeg	Manitoba
India	Centre for Chronic Disease Control	New Delhi
Iran, Islamic Republic of	Isfahan Cardiovascular Research Centre	Isfahan	Iran
Pakistan	InterActive Research and Development	Karachi
Tunisia	University Hospital F. Bourguiba	Sousse
United States	Bay Regional Medical Center	Bay City	Michigan
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Bassett Healthcare	Cooperstown	New York
United States	United Health Services	Johnson City	New York
United States	Schuster Cardiology	Kettering	Ohio
United States	Southwest Cardiology	Kettering	Ohio
United States	Central Maine Medical Center	Lewiston	Maine
United States	Riverside Hospital	Newport News	Virginia
United States	DVA Medical Center	Oklahoma City	Oklahoma
United States	Parkview Medcial Center	Pueblo	Colorado
United States	Advanced Cardiology Specialists	Scranton	Pennsylvania
United States	Charleston Area Medical Center	South Charleston	West Virginia
United States	Stony Brook Hospital and Medical Center	Stony Brook	New York

Sponsors (3)

Lead Sponsor	Collaborator
Mark Eisenberg	Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada

Countries where clinical trial is conducted

United States,  Bangladesh,  Canada,  India,  Iran, Islamic Republic of,  Pakistan,  Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Smoking Abstinence	The primary end point was 7-day point prevalence smoking abstinence at 12 months. Smoking cessation was defined as self-reported abstinence in the week before the 12-month clinic visit and a measurement of exhaled carbon monoxide less than 11 ppm.; The primary end point was analyzed on an intention-to-treat (ITT) basis. Our ITT analysis assumed that those who withdrew consent or were lost to follow-up had returned to smoking at their baseline rates. This assumption is common in smoking cessation trials.	12 months	No
Secondary	Composite Major Adverse Cardiovascular Events (MACE)	All clinical end points were adjudicated by members of the Endpoints Evaluation Committee who were blinded to treatment assignment.; Composite MACE (death, myocardial infarction, unstable angina)	12 months	Yes