The Safety of Transdermal Nicotine Immediately Following an Acute Coronary Syndrome (STADIA)

• ClinicalTrials.gov Identifier: NCT00990197
• Recruitment Status: Suspended
• First Posted: October 6, 2009
• Last Update Posted: October 6, 2009
• Sponsor: Sir Mortimer B. Davis - Jewish General Hospital
• Collaborator: Canadian Tobacco Control Research Initiative
• Information provided by: Sir Mortimer B. Davis - Jewish General Hospital

Study Description

Brief Summary:

Continuing to smoke after having a heart attack greatly increases the risk of death and cardiac illness. The nicotine patch is a commonly used pharmacotherapy for smoking cessation and has great potential to help heart attack patients quit smoking. However, due to safety concerns, physicians are often hesitant to prescribe the nicotine patch to patients who have just suffered a heart attack. The STADIA pilot study will assess the feasibility of a large-scale clinical trial investigating safety and efficacy outcomes associated with the nicotine patch immediately following a heart attack. Eligible subjects will be randomized within 48 hours of suffering a heart attack to wear a transdermal nicotine patch on either day 1 or day 2 of the study period. The nicotine patch will deliver nicotine to the patient over the period of 24 hours. Patients will be advised to discuss smoking cessation strategies with their treating physician and subsequent care will be left to the discretion of this physician. The duration of ischemia (loss of blood flow in the heart), patient adherence, incidence of arrhythmia (disorder of the heart rate or rhythm), heart rate, and blood pressure within the two groups will be used to evaluate the safety of transdermal nicotine use immediately after a heart attack.

Condition or disease	Intervention/treatment	Phase
Smoking Cessation	Drug: Transdermal nicotine patch	Not Applicable

Detailed Description:

Objective

The STADIA Pilot Study will be used to evaluate the feasibility of conducting a three-year multi-centre trial investigating the long-term safety and efficacy outcomes associated with transdermal nicotine use immediately following an acute coronary syndrome (ACS).

Rationale

Patients who initially survive an ACS are at high risk of recurrent cardiac events or cardiovascular death. Within the first 6 months alone, 12% of patients will die or suffer another ACS, while another 23% will require revascularization for angina. Patients who are able to quit smoking reduce their chances of suffering a recurrent ACS or cardiovascular death within the next year by ≥ 50%. After surviving an ACS, most patients are highly motivated to stop smoking. However, as nicotine is an extremely addictive psychoactive drug, up to 60% of patients who attempt to quit relapse. Hospitalization following an ACS provides an opportunity for smokers to quit, as smoking while in hospital is prohibited. However, abstinence while hospitalized also precipitates intense nicotine withdrawal symptoms, which are largely responsible for the high rates of smoking relapse. Nicotine replacement therapy (NRT) can ameliorate many of these symptoms and increase the chances that smokers continue to abstain from tobacco use after discharge. Of the available NRTs, transdermal nicotine is associated with the least severe cardiovascular effects, as it delivers nicotine more gradually (with lower peak values) than nicotine gum or inhalers. Although transdermal nicotine more than doubles long-term smoking cessation rates when compared with placebo, it is rarely prescribed by physicians in the weeks immediately following an ACS because the possible cardiovascular effects of nicotine after an ACS have yet to be systematically evaluated.

Methods

A total of 30 patients will be randomized within 48-hours of suffering an ACS from the Jewish General Hospital (Montreal, QC) and collaborating centres. Prior to randomization, all patients will receive standardized smoking cessation counselling. Subjects who satisfy the inclusion and exclusion criteria for the trial will be randomized within 48 hours of suffering an ACS to wear a transdermal nicotine patch on either day 1 or day 2 of the study period. Subjects will apply a patch the morning of their treatment day and keep it on for 24 hours. Patients will be advised to discuss smoking cessation strategies with their treating physician and subsequent care will be left to the discretion of this physician. Twenty-four hour Holter monitoring will be used to measure heart rate, incidence of arrhythmia, and the duration of ischemic events at day 1 and day 2 of the study period. Systolic and diastolic blood pressure will be assessed via 24-hour Ambulatory blood pressure monitoring (ABPM). ABPM will be used on day 1 and day 2 of the study period. On day 1 the study nurse will record the severity of nicotine withdrawal symptoms, side effects, any smoking relapses and if so, how many cigarettes were smoked, and any medications they are currently taking. On day 7 and 14 patients will be contacted by telephone to determine the severity of nicotine withdrawal symptoms, any smoking relapses and if so, how many cigarettes were smoked and any medications they are currently taking. Cardiovascular events will be assessed by patient monitoring and by a study nurse. Nicotine withdrawal symptoms according to the Hughes-Hatsukami symptom scale and common nicotine patch side effects, severity-rated on a five-point scale, will be determined through study nurse inquiries on days 1, 7, and 14 (6). Carbon monoxide monitors will be used to measure levels of expired CO at baseline. Participants whose levels of expired CO exceed 10 ppm will be classified as smokers.

Significance

If shown to be safe and effective, transdermal nicotine will have a major impact on the secondary prevention of recurrent cardiac events on the 20,000 Canadian smokers who suffer an ACS each year.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Safety of Transdermal Nicotine Immediately Following an Acute Coronary Syndrome: The STADIA Pilot Study
• Study Start Date: June 2005
• Estimated Primary Completion Date: July 2009
• Estimated Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Day 1; Patients randomized to wearing the patch on day 1 will apply a patch on the morning of their treatment day and keep it on for 24 hours. These patients will not wear a patch on day 2.	Drug: Transdermal nicotine patch; Subjects will apply the nicotine patch on the morning of their treatment day and will keep it on for 24 hours.; Other Name: Nicoderm CQ, Biovail Pharmaceuticals
Active Comparator: Day 2; Patients randomized to wearing the patch on day 2 will apply a patch on the morning of their treatment day and keep it on for 24 hours. These patients will not wear a patch on day 1.	Drug: Transdermal nicotine patch; Subjects will apply the nicotine patch on the morning of their treatment day and will keep it on for 24 hours.; Other Name: Nicoderm CQ, Biovail Pharmaceuticals

Outcome Measures

Primary Outcome Measures :

1. The total duration of ischemic episodes [ Time Frame: Day 1 and Day 2 ]

Secondary Outcome Measures :

1. Patient adherence to study protocol [ Time Frame: Day 1, Day 7, Day 14 ]
2. Incidence of arrhythmia [ Time Frame: Day 1 and Day 2 ]
3. Heart rate [ Time Frame: Day 1 and Day 2 ]
4. Systolic and diastolic blood pressure [ Time Frame: Day 1 and Day 2 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 years
• Current smoker, ≥ 10 cigarettes per day, on average, for the past year
• Suffered an enzyme-positive ACS (Troponin T, Troponin I, or CK-MD) and planned hospitalization of ≥ 48 hours
• Motivated to quit smoking

Exclusion Criteria:

• Current use of any medical therapy for smoking cessation
• History of alcohol or controlled substance abuse
• History of severe dermatitis
• Current diagnosis of unstable psychiatric illness requiring medication
• Suffered an ACS as a complication of a hospitalization for a different condition (i.e. postoperatively)
• Pregnancy or lactation
• Likely to be unavailable for follow-up
• Unable to read and understand English or French

Contacts and Locations

Locations

Canada, Quebec

SMDB Jewish General Hospital

Montreal, Quebec, Canada, H3T 1E2

Sponsors and Collaborators

Sir Mortimer B. Davis - Jewish General Hospital

Canadian Tobacco Control Research Initiative

Investigators

• Principal Investigator: Mark J Eisenberg, MD MPH; Jewish General Hospital/McGill University

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• Responsible Party: Mark J. Eisenberg, MD MPH, Jewish General Hospital/McGill University
• ClinicalTrials.gov Identifier: NCT00990197
• Other Study ID Numbers: 05-023; 016026
• First Posted: October 6, 2009
• Last Update Posted: October 6, 2009
• Last Verified: October 2009

Keywords provided by Sir Mortimer B. Davis - Jewish General Hospital:

Pilot study; Randomized clinical trial; Smoking cessation; Acute coronary syndrome; Transdermal nicotine patch

Additional relevant MeSH terms:

Acute Coronary Syndrome; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action