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

NCT ID: NCT00689611

Last Updated: 2015-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 392 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-06-30

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.

Conditions

Acute Coronary Syndrome; Myocardial Infarction; Smoking

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

P

Half of patients will receive placebo for 9 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

A

Half of patients will receive bupropion for 9 weeks.

Group Type: ACTIVE_COMPARATOR

Bupropion HCl ER

Intervention Type: DRUG

150 mg tablets po qd for 3 days and then 150 mg po bid for remainder of 9 weeks

Interventions

Bupropion HCl ER

150 mg tablets po qd for 3 days and then 150 mg po bid for remainder of 9 weeks

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Zyban

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Heart and Stroke Foundation of Canada

OTHER

Sponsor Role: collaborator

Mark Eisenberg

OTHER

Sponsor Role: lead

Responsible Party

Mark Eisenberg

MD, MPH, Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mark J Eisenberg, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital/ McGill University

Locations

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

Medical University of South Carolina

Charleston, South Carolina, United States

Riverside Hospital

Newport News, Virginia, United States

Charleston Area Medical Center

South Charleston, West Virginia, United States

National Heart Foundation of Bangladesh

Dhaka, , Bangladesh

Peter Lougheed Centre of the Calgary General Hospital

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Vancouver Coastal Health

Vancouver, British Columbia, Canada

Victoria General Hospital

Winnipeg, Manitoba, Canada

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

New Brunswick Heart Centre

Saint Johns, New Brunswick, Canada

Valley Regional Hospital

Kentville, Nova Scotia, Canada

The Ottawa Hospital, General Campus

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Hopital de la Cite de la Sante

Laval, Quebec, Canada

CHA Hotel-Dieu de Levis

Lévis, Quebec, Canada

SMBD- Jewish General Hospital

Montreal, Quebec, Canada

Hopital Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Hotel-Dieu

Montreal, Quebec, Canada

Montreal General Hospital

Montreal, Quebec, Canada

Hopital Laval

Québec, Quebec, Canada

Hopital Fleurimont

Sherbrooke, Quebec, Canada

CSSS de Sorel-Tracy

Sorel-Tracy, Quebec, Canada

CSSS de la Region de Thetford

Thetford-Mines, Quebec, Canada

Saskatchewan Drug Research Institute

Saskatoon, Saskatchewan, Canada

Centre for Chronic Disease Control

New Delhi, , India

Isfahan Cardiovascular Research Centre

Isfahan, Iran, Iran

InterActive Research and Development

Karachi, , Pakistan

University Hospital F. Bourguiba

Sousse, Sousse Governorate, Tunisia

Countries

United States; Bangladesh; Canada; India; Iran; Pakistan; Tunisia

References

Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 10.1002/14651858.CD000031.pub6.

Reference Type: DERIVED

PMID: 37230961 (View on PubMed)

Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.

Reference Type: DERIVED

PMID: 34611902 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33687070 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25326910 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24440324 (View on PubMed)

Other Identifiers

ISRCTN75356261

Identifier Type: -

Identifier Source: secondary_id

ZESCA 9197

Identifier Type: -

Identifier Source: org_study_id