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

Phase 3

Completed

Conditions: Acute Coronary Syndrome
Myocardial Infarction
Smoking

Interventions: Drug: Placebo
Drug: Bupropion HCl ER

Registration Number: NCT00689611

Lead Sponsor: Mark Eisenberg

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 392

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
P	Placebo	Half of patients will receive placebo for 9 weeks.
A	Bupropion HCl ER	Half of patients will receive bupropion for 9 weeks.

Primary Outcome Measures

Name	Time	Method
Smoking Abstinence	12 months	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.

Secondary Outcome Measures

Name	Time	Method
Composite Major Adverse Cardiovascular Events (MACE)	12 months	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)

Trial Locations

Locations (38): Parkview Medcial Center
🇺🇸
Pueblo, Colorado, United States
Central Maine Medical Center
🇺🇸
Lewiston, Maine, United States
Bay Regional Medical Center
🇺🇸
Bay City, Michigan, United States
Bassett Healthcare
🇺🇸
Cooperstown, New York, United States
United Health Services
🇺🇸
Johnson City, New York, United States
Stony Brook Hospital and Medical Center
🇺🇸
Stony Brook, New York, United States
Schuster Cardiology
🇺🇸
Kettering, Ohio, United States
Southwest Cardiology
🇺🇸
Kettering, Ohio, United States
DVA Medical Center
🇺🇸
Oklahoma City, Oklahoma, United States
Advanced Cardiology Specialists
🇺🇸
Scranton, Pennsylvania, United States
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Parkview Medcial Center
🇺🇸Pueblo, Colorado, United States