Clinical trial NCT00689611: Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome: The ZESCA Trial
Official title: Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome: The ZESCA Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Myocardial Infarction
Smoking
Keywords: Acute coronary syndrome
Myocardial infarction
Smoking cessation
Zyban
Secondary intervention post-ACS
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Heart and Stroke Foundation of Canada
First posted: 2008-06-03
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Smoking Abstinence
timeFrame: 12 months
Secondary outcomes:
measure: Composite Major Adverse Cardiovascular Events (MACE)
timeFrame: 12 months
Other outcomes:
Locations:
city: Pueblo
country: United States
facility: Parkview Medcial Center
state: Colorado
city: Lewiston
country: United States
facility: Central Maine Medical Center
state: Maine
city: Bay City
country: United States
facility: Bay Regional Medical Center
state: Michigan
city: Cooperstown
country: United States
facility: Bassett Healthcare
state: New York
city: Johnson City
country: United States
facility: United Health Services
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Hospital and Medical Center
state: New York
city: Kettering
country: United States
facility: Schuster Cardiology
state: Ohio
city: Kettering
country: United States
facility: Southwest Cardiology
state: Ohio
city: Oklahoma City
country: United States
facility: DVA Medical Center
state: Oklahoma
city: Scranton
country: United States
facility: Advanced Cardiology Specialists
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Newport News
country: United States
facility: Riverside Hospital
state: Virginia
city: South Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Dhaka
country: Bangladesh
facility: National Heart Foundation of Bangladesh
city: Calgary
country: Canada
facility: Peter Lougheed Centre of the Calgary General Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health
state: British Columbia
city: Winnipeg
country: Canada
facility: Victoria General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Saint Johns
country: Canada
facility: New Brunswick Heart Centre
state: New Brunswick
city: Kentville
country: Canada
facility: Valley Regional Hospital
state: Nova Scotia
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Laval
country: Canada
facility: Hopital de la Cite de la Sante
state: Quebec
city: Levis
country: Canada
facility: CHA Hotel-Dieu de Levis
state: Quebec
city: Montreal
country: Canada
facility: SMBD- Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sacre-Coeur de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Hotel-Dieu
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: Hopital Fleurimont
state: Quebec
city: Sorel
country: Canada
facility: CSSS de Sorel-Tracy
state: Quebec
city: Thetford Mines
country: Canada
facility: CSSS de la Region de Thetford
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatchewan Drug Research Institute
state: Saskatchewan
city: Quebec
country: Canada
facility: Hopital Laval
city: New Delhi
country: India
facility: Centre for Chronic Disease Control
city: Isfahan
country: Iran, Islamic Republic of
facility: Isfahan Cardiovascular Research Centre
state: Iran
city: Karachi
country: Pakistan
facility: InterActive Research and Development
city: Sousse
country: Tunisia
facility: University Hospital F. Bourguiba
Study officials:
affiliation: Jewish General Hospital/ McGill University
name: Mark J Eisenberg, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Taylor GM, Lindson N, Farley A, Leinberger-Jabari A, Sawyer K, Te Water Naude R, Theodoulou A, King N, Burke C, Aveyard P. Smoking cessation for improving mental health. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD013522. doi: 10.1002/14651858.CD013522.pub2.
citation: Zhang DD, Eisenberg MJ, Grandi SM, Joseph L, O'Loughlin J, Paradis G, Lozano P, Filion KB. Bupropion, smoking cessation, and health-related quality of life following an acute myocardial infarction. J Popul Ther Clin Pharmacol. 2014;21(3):e346-56. Epub 2014 Oct 8.
citation: Shimony A, Grandi SM, Pilote L, Joseph L, O'Loughlin J, Paradis G, Rinfret S, Sarrafzadegan N, Adamjee N, Yadav R, Gamra H, Diodati JG, Eisenberg MJ; ZESCA Investigators. Utilization of evidence-based therapy for acute coronary syndrome in high-income and low/middle-income countries. Am J Cardiol. 2014 Mar 1;113(5):793-7. doi: 10.1016/j.amjcard.2013.11.024. Epub 2013 Dec 12.