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

Condition(s) targeted: Acute Coronary Syndrome; Myocardial Infarction; Smoking

Intervention: Bupropion HCl ER (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: McGill University

Official(s) and/or principal investigator(s):
Mark J Eisenberg, MD, MPH, Principal Investigator, Affiliation: Jewish General Hospital/ McGill University

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.

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

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

Primary outcome: To examine the impact of bupropion (Zyban) on smoking cessation rates at one year following an enzyme-positive acute coronary syndrome (ACS).

Secondary outcome: To examine the safety of sustained release bupropion in patients following an acute coronary syndrome.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

National Heart Foundation of Bangladesh, Dhaka, Bangladesh; Active, not recruiting

Centre for Chronic Disease Control, New Delhi, India; Recruiting
Anuradha Tripathi, MD, Phone: + 9111 26850117, Email: anuradha@ccdcindia.org
D Prabhakaran, MD, DM, MSc, Principal Investigator

University Hospital F. Bourguiba, Sousse, Tunisia; Recruiting
Hassen Ghannem, MD, Phone: +21673219496, Email: hassen.ghannem@rns.tn
Hassen Ghannem, MD, Principal Investigator

Peter Lougheed Centre of the Calgary General Hospital, Calgary, Alberta, Canada; Recruiting
Peggy Beresford, RN, Phone: 403-943-4524, Email: peggy.beresford@calgaryhealthregion.ca
Peter Giannoccaro, MD, Principal Investigator

University of Alberta Hospital, Edmonton, Alberta, Canada; Recruiting
Bonnie Woloschuk, RN, Phone: 780-492-4860, Email: bonniew@ualberta.ca
Ian Paterson, MD, Principal Investigator

Scottsdale Cardiovascular Research Institute, Scottsdale, Arizona, United States; Recruiting
Dewayne Thurmond, RN, Phone: 480-248-3377, Email: dthurmond@scresearch.org
Krishnaswami Vijayaraghavan, MD, Principal Investigator

DC VA Medical Center, Washington, District of Columbia, United States; Recruiting
Helen Sheriff, RN, Phone: 202-745-8000, Ext: 7288, Email: helen.sheriff@va.gov
Michael Greenberg, MD, Principal Investigator

Isfahan Cardiovascular Research Centre, Isfahan, Iran, Iran, Islamic Republic of; Active, not recruiting

St. Boniface General Hospital, Winnipeg, Manitoba, Canada; Recruiting
Noreen Garanhel, RN, Phone: 204-237-2705, Email: ngaranhel@sbgh.mb.ca
Sat Sharma, MD, Principal Investigator

Bay Regional Medical Center, Bay City, Michigan, United States; Recruiting
Suzanne Vasquez, RN, Phone: 989-894-8616, Email: suzannevasquez@bhsnet.org
Kochunni Mohan, MD, Principal Investigator

New Brunswick Heart Centre, Saint Johns, New Brunswick, Canada; Recruiting
Elizabeth Collings, RN, Phone: 506- 648-7121, Email: colel@reg2.health.nb.ca
Sohrab Lutchmedial, MD, Principal Investigator

Valley Regional Hospital, Kentville, Nova Scotia, Canada; Recruiting
Judy Dewolfe, RN, Phone: 902-679-2657, Ext: 1360, Email: jdewolfe@avdha.nshealth.ca
Howard Wightman, MD, Principal Investigator

The Ottawa Hospital, General Campus, Ottawa, Ontario, Canada; Recruiting
Julie Finnigan, RN, Phone: 613-737-8135, Email: jfinnigan@ottawahospital.on.ca
Andreas Wielgosz, MD, Principal Investigator

St. Michael's Hospital, Toronto, Ontario, Canada; Recruiting
Larah Ross, MD, Phone: 416-864-6060, Ext: 6161, Email: rossl@smh.toronto.on.ca
Beth Abramson, MD, Principal Investigator

CHA Hotel-Dieu de Levis, Levis, Quebec, Canada; Recruiting
Francine Dumont, RN, Phone: 418-833-5750, Email: clincardiolevis@bellnet.ca
Francois Grondin, MD, Principal Investigator

Montreal General Hospital, Montreal, Quebec, Canada; Recruiting
Nancy Branco, RN, Phone: 514-934-1934, Ext: 44649, Email: nancy.branco@muhc.mcgill.ca
Louise Pilote, MD, MPH, PhD, Principal Investigator

Hotel-Dieu, Montreal, Quebec, Canada; Recruiting
Renee Duclos, RN, Phone: 514-890-8000, Ext: 14803, Email: recherche.cardio.hd.chum@ssss.gouv.qc.ca
Paolo Costi, MD, Principal Investigator

Hopital Sacre-Coeur de Montreal, Montreal, Quebec, Canada; Recruiting
Celine Groulx, RN, Phone: 514-338-2222, Ext: 3083, Email: c-groulx@crhsc.umontreal.ca
Jean Diodati, MD, Principal Investigator

SMBD- Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada; Recruiting
Sonia Grandi, MSc, Phone: 514-340-8222, Ext: 3240, Email: sonia.grandi@mail.mcgill.ca
Mark J Eisenberg, MD, MPH, Phone: 514-340-8222, Ext: 3564, Email: mark.eisenberg@mcgill.ca
Mark J Eisenberg, MD, MPH, Principal Investigator

CSSS de Sorel-Tracy, Sorel, Quebec, Canada; Active, not recruiting

CSSS de la Region de Thetford, Thetford Mines, Quebec, Canada; Recruiting
Francine Dumont, RN, Phone: 418-338-7740, Email: IRA_inc@hotmail.com
Claude Lauzon, MD, Principal Investigator

Starting date: December 2005
Last updated: May 30, 2008