The Safety of Transdermal Nicotine Immediately Following an Acute Coronary Syndrome

Smoking Cessation Clinical Trial

— STADIA  

Official title:

The Safety of Transdermal Nicotine Immediately Following an Acute Coronary Syndrome: The STADIA Pilot Study

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00990197
• Other study ID #: 05-023
• Secondary ID: 016026
• Status: Suspended
• Phase: N/A
• First received: October 5, 2009
• Last updated: October 5, 2009
• Start date: June 2005
• Est. completion date: December 2009

Study information

• Verified date: October 2009
• Source: Sir Mortimer B. Davis - Jewish General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Canadian Institutes of Health ResearchCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Est. completion date: December 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Smoking Cessation

Intervention

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.

Locations

Country	Name	City	State
Canada	SMDB Jewish General Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Sir Mortimer B. Davis - Jewish General Hospital	Canadian Tobacco Control Research Initiative

Country where clinical trial is conducted

Canada, 

References & Publications (56)

Allen SS, Hatsukami D, Gorsline J. Cholesterol changes in smoking cessation using the transdermal nicotine system. Transdermal Nicotine Study Group. Prev Med. 1994 Mar;23(2):190-6. — View Citation

Allred EN, Bleecker ER, Chaitman BR, Dahms TE, Gottlieb SO, Hackney JD, Pagano M, Selvester RH, Walden SM, Warren J. Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease. N Engl J Med. 1989 Nov 23;321(21):1426-32. Erratum in: N Engl J Med 1990 Apr 5;322(14):1019. — View Citation

American Medical Association. Drug Evaluations Annual 1994. Chicago: American Medical Association 1993.

Arnaot MR. Treating heart disease. Nicotine patches may not be safe. BMJ. 1995 Mar 11;310(6980):663-4. — View Citation

Barnes PJ. New concepts in chronic obstructive pulmonary disease. Annu Rev Med. 2003;54:113-29. Epub 2001 Dec 3. Review. — View Citation

Benowitz NL, Fitzgerald GA, Wilson M, Zhang Q. Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. J Am Coll Cardiol. 1993 Oct;22(4):1159-67. — View Citation

Benowitz NL. Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addition. N Engl J Med. 1988 Nov 17;319(20):1318-30. Review. — View Citation

Brummett BH, Babyak MA, Mark DC, Williams RB, Siegler IC, Clapp-Channing N, Barefoot JC. Predictors of smoking cessation in patients with a diagnosis of coronary artery disease. J Cardiopulm Rehabil. 2002 May-Jun;22(3):143-7. — View Citation

Cardiovascular Disease Surveillance. Laboratory Centre for Disease Control, Statistics Canada 2002, Candian Institutes for Health Information (CIHI), 2002.

Dacosta A, Guy JM, Tardy B, Gonthier R, Denis L, Lamaud M, Cerisier A, Verneyre H. Myocardial infarction and nicotine patch: a contributing or causative factor? Eur Heart J. 1993 Dec;14(12):1709-11. — View Citation

Fiore MC, Smith SS, Jorenby DE, Baker TB. The effectiveness of the nicotine patch for smoking cessation. A meta-analysis. JAMA. 1994 Jun 22-29;271(24):1940-7. — View Citation

Fiore MC. US public health service clinical practice guideline: treating tobacco use and dependence. Respir Care. 2000 Oct;45(10):1200-62. Review. — View Citation

Fredrickson PA, Hurt RD, Lee GM, Wingender L, Croghan IT, Lauger G, Gomez-Dahl L, Offord KP. High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Psychopharmacology (Berl). 1995 Dec;122(3):215-22. — View Citation

Freedman D PRPR. Statistics. New York: Norton Publishers, 1978.

Frid D, Ockene IS, Ockene JK, Merriam P, Goldberg R, Kristeller J, Barrett S. Severity of angiographically proven coronary artery disease predicts smoking cessation. Am J Prev Med. 1991 May-Jun;7(3):131-5. — View Citation

Gillum RF, Ingram DD, Makuc DM. White blood cell count and stroke incidence and death. The NHANES I epidemiologic follow-up study. Am J Epidemiol. 1994 May 1;139(9):894-902. — View Citation

Gourlay S. The pros and cons of transdermal nicotine therapy. Med J Aust. 1994 Feb 7;160(3):152-9. Review. — View Citation

Greenland S, Satterfield MH, Lanes SF. A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Saf. 1998 Apr;18(4):297-308. — View Citation

Grimm RH Jr, Neaton JD, Ludwig W. Prognostic importance of the white blood cell count for coronary, cancer, and all-cause mortality. JAMA. 1985 Oct 11;254(14):1932-7. — View Citation

Hansen PR. Role of neutrophils in myocardial ischemia and reperfusion. Circulation. 1995 Mar 15;91(6):1872-85. Review. — View Citation

Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. — View Citation

Hughes JR, Glaser M. Transdermal nicotine for smoking cessation. Health Values 1993; 17(2):25-31.

Hughes JR. Tobacco withdrawal in self-quitters. J Consult Clin Psychol. 1992 Oct;60(5):689-97. — View Citation

Hwang SL WM. Heart attacks reported in patch users still smoking. Wall Street Journal 1992;(June 19):B1.

Jackson M. Cerebral arterial narrowing with nicotine patch. Lancet. 1993 Jul 24;342(8865):236-7. — View Citation

Jorenby DE, Hatsukami DK, Smith SS, Fiore MC, Allen S, Jensen J, Baker TB. Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain. Psychopharmacology (Berl). 1996 Nov;128(2):130-8. — View Citation

Jorenby DE, Smith SS, Fiore MC, Hurt RD, Offord KP, Croghan IT, Hays JT, Lewis SF, Baker TB. Varying nicotine patch dose and type of smoking cessation counseling. JAMA. 1995 Nov 1;274(17):1347-52. — View Citation

Joseph AM, Norman SM, Ferry LH, Prochazka AV, Westman EC, Steele BG, Sherman SE, Cleveland M, Antonuccio DO, Hartman N, McGovern PG. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med. 1996 Dec 12;335(24):1792-8. Erratum in: N Engl J Med. 2007 Jun 14;356(24):2554. Antonnucio, DO [corrected to Antonuccio, DO]. — View Citation

Kaijser L, Berglund B. Effect of nicotine on coronary blood-flow in man. Clin Physiol. 1985 Dec;5(6):541-52. — View Citation

Longo LD. The biological effects of carbon monoxide on the pregnant woman, fetus, and newborn infant. Am J Obstet Gynecol. 1977 Sep 1;129(1):69-103. — View Citation

Mahmarian JJ, Moyé LA, Nasser GA, Nagueh SF, Bloom MF, Benowitz NL, Verani MS, Byrd WG, Pratt CM. Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia. J Am Coll Cardiol. 1997 Jul;30(1):125-30. — View Citation

Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ 2nd. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N Engl J Med. 1995 May 4;332(18):1198-203. — View Citation

Moyer D. Chapter 13: Physical fitness and carbon monoxide. Tobacco Reference Guide 2000;30-34.

Mulligan SC, Masterson JG, Devane JG, Kelly JG. Clinical and pharmacokinetic properties of a transdermal nicotine patch. Clin Pharmacol Ther. 1990 Mar;47(3):331-7. — View Citation

Nicotine replacement therapy for patients with coronary artery disease. Working Group for the Study of Transdermal Nicotine in Patients with Coronary artery disease. Arch Intern Med. 1994 May 9;154(9):989-95. — View Citation

Ottervanger JP, Festen JM, de Vries AG, Stricker BH. Acute myocardial infarction while using the nicotine patch. Chest. 1995 Jun;107(6):1765-6. — View Citation

Palatini P, Pessina AC, Graniero GR, Canali C, Mormino P, Dorigatti F, Accurso V, Michieletto M, Ferrarese E, Vriz O, et al. [The relationship between overweight, life style and casual and 24-hour pressures in a population of male subjects with mild hypertension. The results of the HARVEST study]. G Ital Cardiol. 1995 Aug;25(8):977-89. Italian. — View Citation

Palmer KJ, Buckley MM, Faulds D. Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Drugs. 1992 Sep;44(3):498-529. Review. — View Citation

Peters RW, Benowitz NL, Valenti S, Modin G, Fisher ML. Electrophysiologic effects of cigarette smoking in patients with and without chronic beta-blocker therapy. Am J Cardiol. 1987 Nov 1;60(13):1078-82. — View Citation

Pickering TG, Schwartz JE, James GD. Ambulatory blood pressure monitoring for evaluating the relationships between lifestyle, hypertension and cardiovascular risk. Clin Exp Pharmacol Physiol. 1995 Mar;22(3):226-31. Review. — View Citation

Pierce JR Jr. Stroke following application of a nicotine patch. Ann Pharmacother. 1994 Mar;28(3):402. — View Citation

Rietbrock N, Kunkel S, Wörner W, Eyer P. Oxygen-dissociation kinetics in the blood of smokers and non-smokers: interaction between oxygen and carbon monoxide at the hemoglobin molecule. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jan;345(1):123-8. — View Citation

Rigotti NA, Arnsten JH, McKool KM, Wood-Reid KM, Pasternak RC, Singer DE. Smoking by patients in a smoke-free hospital: prevalence, predictors, and implications. Prev Med. 2000 Aug;31(2 Pt 1):159-66. — View Citation

Sauer WH, Berlin JA, Strom BL, Miles C, Carson JL, Kimmel SE. Cigarette yield and the risk of myocardial infarction in smokers. Arch Intern Med. 2002 Feb 11;162(3):300-6. — View Citation

Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2001;(3):CD000146. Review. Update in: Cochrane Database Syst Rev. 2002;(4):CD000146. — View Citation

Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2002;(4):CD000146. Review. Update in: Cochrane Database Syst Rev. 2004;(3):CD000146. — View Citation

Silagy C, Mant D, Fowler G, Lodge M. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet. 1994 Jan 15;343(8890):139-42. — View Citation

Stapleton J. Cigarette smoking prevalence, cessation and relapse. Stat Methods Med Res. 1998 Jun;7(2):187-203. — View Citation

Tang JL, Law M, Wald N. How effective is nicotine replacement therapy in helping people to stop smoking? BMJ. 1994 Jan 1;308(6920):21-6. Erratum in: BMJ 1994 Mar 5;308(6929):626. — View Citation

Transdermal nicotine for smoking cessation. Six-month results from two multicenter controlled clinical trials. Transdermal Nicotine Study Group. JAMA. 1991 Dec 11;266(22):3133-8. — View Citation

Treating tobacco dependence: a report of the Surgeon General. Washington, DC: Department of Health and Human Services, 2000.

Tzivoni D, Keren A, Meyler S, Khoury Z, Lerer T, Brunel P. Cardiovascular safety of transdermal nicotine patches in patients with coronary artery disease who try to quit smoking. Cardiovasc Drugs Ther. 1998 Jul;12(3):239-44. — View Citation

Warner JG Jr, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med. 1994 Apr 15;120(8):695. — View Citation

Wilson K, Gibson N, Willan A, Cook D. Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies. Arch Intern Med. 2000 Apr 10;160(7):939-44. — View Citation

Zevin S, Benowitz NL. Drug interactions with tobacco smoking. An update. Clin Pharmacokinet. 1999 Jun;36(6):425-38. Review. — View Citation

Zevin S, Jacob P 3rd, Benowitz NL. Dose-related cardiovascular and endocrine effects of transdermal nicotine. Clin Pharmacol Ther. 1998 Jul;64(1):87-95. — View Citation

* Note: There are 56 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The total duration of ischemic episodes		Day 1 and Day 2	Yes
Secondary	Patient adherence to study protocol		Day 1, Day 7, Day 14	No
Secondary	Incidence of arrhythmia		Day 1 and Day 2	Yes
Secondary	Heart rate		Day 1 and Day 2	Yes
Secondary	Systolic and diastolic blood pressure		Day 1 and Day 2	Yes