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

This study has been completed.
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Quebec
Information provided by (Responsible Party):
Mark Eisenberg, McGill University
ClinicalTrials.gov Identifier:
NCT00689611
First received: May 30, 2008
Last updated: April 24, 2012
Last verified: May 2008
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Myocardial Infarction
Smoking
Drug: Bupropion HCl ER
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome: The ZESCA Trial

Resource links provided by NLM:


Further study details as provided by McGill University:

Primary Outcome Measures:
  • To examine the impact of bupropion (Zyban) on smoking cessation rates at one year following an enzyme-positive acute coronary syndrome (ACS). [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To examine the safety of sustained release bupropion in patients following an acute coronary syndrome. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 392
Study Start Date: December 2005
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: P
Half of patients will receive placebo for 9 weeks.
Drug: Placebo
Placebo
Active Comparator: A
Half of patients will receive bupropion for 9 weeks.
Drug: Bupropion HCl ER
150 mg tablets po qd for 3 days and then 150 mg po bid for remainder of 9 weeks
Other Name: Zyban

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00689611

  Show 38 Study Locations
Sponsors and Collaborators
Mark Eisenberg
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Quebec
Investigators
Principal Investigator: Mark J Eisenberg, MD, MPH Jewish General Hospital/ McGill University
  More Information

No publications provided

Responsible Party: Mark Eisenberg, MD, MPH, Professor of Medicine, McGill University
ClinicalTrials.gov Identifier: NCT00689611     History of Changes
Other Study ID Numbers: ZESCA 9197, ISRCTN75356261
Study First Received: May 30, 2008
Last Updated: April 24, 2012
Health Authority: Canada: Health Canada

Keywords provided by McGill University:
Acute coronary syndrome
Myocardial infarction
Smoking cessation
Zyban
Secondary intervention post-ACS

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Smoking
Acute Coronary Syndrome
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Habits
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Bupropion
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 20, 2014