The Efficacy of Influenza Vaccine in Reducing Cardiovascular Events in Patients With Coronary Artery Diseases

NCT ID: NCT00607178

Last Updated: 2009-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2008-09-30

Brief Summary

Influenza vaccine reduces the cardiovascular events in post-myocardial infarction (MI) patients and in those with stable angina (SA).

Detailed Description

A connection between infectious processes and atherosclerosis is repeatedly reported [1]. Acute respiratory infection was found to be associated with myocardial infarction (MI) [2,3] and a number of epidemiological studies found that mortality attributable to cardiovascular diseases is increased during influenza epidemics [4]. Naghavi et al [5] in a case-control study of patients with coronary artery disease (CAD) found that vaccination against influenza was negatively associated with the development of new MI during the same influenza season. While some clinical trials found influenza vaccine effective in secondary prevention of cardiovascular adverse events [6,7], a large trial [8] failed to approve such an efficacy. Furthermore, a recent review of published trials on the subject concluded that frailty selection bias and use of non-specific endpoints such as all cause mortality have led cohort studies to greatly exaggerate vaccine benefits and that the remaining evidence base is currently insufficient to indicate the magnitude of the mortality benefit of the vaccination program [9].

This study aims to assess the efficacy of vaccine in secondary prevention of cardiovascular events in MI and stable angina (SA) patients using specific endpoints including reliable quantitative tools.

Conditions

Coronary Artery Diseases; Myocardial Infarction; Stable Angina

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Influenza vaccine

Enrolled patients who are randomly assigned to receive influenza vaccine

Group Type: EXPERIMENTAL

influenza vaccine

Intervention Type: BIOLOGICAL

Intramuscular injection of one 0.5-mL dose of influenza vaccine

Placebo

Enrolled patients who are randomly assigned to receive placebo of influenza vaccine

Group Type: PLACEBO_COMPARATOR

placebo for influenza vaccine

Intervention Type: BIOLOGICAL

Intramuscular injection of one 0.5-mL dose of placebo for influenza vaccine

Interventions

influenza vaccine

Intramuscular injection of one 0.5-mL dose of influenza vaccine

Intervention Type: BIOLOGICAL

placebo for influenza vaccine

Intramuscular injection of one 0.5-mL dose of placebo for influenza vaccine

Intervention Type: BIOLOGICAL

Other Intervention Names

2006-2007 vaccination campaign of Influvac (SolvayPharma)

Eligibility Criteria

Inclusion Criteria

• Patients with the diagnosis of acute, evolving or recent MI (after recovered the acute phase) as defined by:

1. Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:

• Ischemic symptoms
• Development of pathologic Qwaves on the ECG
• ECG changes indicative of ischemia (ST segment elevation or depression); OR
• Coronary artery intervention (e.g., coronary angioplasty).

2. Pathologic findings of an acute MI [12]

• Patients with stable angina pectoris and documented coronary artery stenosis (angiography).

Exclusion Criteria

• Any acute disease
• Chronic liver or kidney diseases
• Conditions accompanied by immunosuppression (like organ transplantation, HIV)
• Diagnosed malignancy
• Incubation with influenza vaccine within the past 5 years
• Any psychological disease that interferes with regular follow-up
• Congestive heart failure (Killip class IV)
• Unstable angina, and contradictions of vaccine incubation (like egg allergy).

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shahid Beheshti University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Infectious Diseases and Tropical Medicine Research Center, SBMU, Tehran, Iran

Principal Investigators

Maryam Keshtkar-Jahromi, M.D.; M.P.H.

Role: STUDY_CHAIR

Infectious Diseases and Tropical Medicine Research Center, Shaheed Beheshti Medical University, Tehran, Iran

Hossein Vakili, M.D.

Role: PRINCIPAL_INVESTIGATOR

Cardiovascular Research Center, Shaheed Beheshti Medical University, Tehran, Iran

Ali Eskandari, MD

Role: PRINCIPAL_INVESTIGATOR

Shahid Beheshti University of Medical Sciences

Mohammad Rahnavardi, MD

Role: PRINCIPAL_INVESTIGATOR

Shahid Beheshti University of Medical Sciences

Sharareh Gholamin, MD

Role: PRINCIPAL_INVESTIGATOR

Shaheed Beheshti University (MC)

Seyed Mostafa Razavi, MD

Role: PRINCIPAL_INVESTIGATOR

Shaheed Beheshti University (MC)

Locations

Shaheed Modarres Medical Center

Tehran, Tehran Province, Iran

Countries

Iran

References

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Reference Type: BACKGROUND

PMID: 16375635 (View on PubMed)

Spodick DH, Flessas AP, Johnson MM. Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol. 1984 Feb 1;53(4):481-2. doi: 10.1016/0002-9149(84)90016-x.

Reference Type: BACKGROUND

PMID: 6695777 (View on PubMed)

Bainton D, Jones GR, Hole D. Influenza and ischaemic heart disease--a possible trigger for acute myocardial infarction? Int J Epidemiol. 1978 Sep;7(3):231-9. doi: 10.1093/ije/7.3.231.

Reference Type: BACKGROUND

PMID: 721358 (View on PubMed)

Gurevich VS. Influenza, autoimmunity and atherogenesis. Autoimmun Rev. 2005 Feb;4(2):101-5. doi: 10.1016/j.autrev.2004.10.006. Epub 2004 Nov 20.

Reference Type: BACKGROUND

PMID: 15722256 (View on PubMed)

Naghavi M, Barlas Z, Siadaty S, Naguib S, Madjid M, Casscells W. Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation. 2000 Dec 19;102(25):3039-45. doi: 10.1161/01.cir.102.25.3039.

Reference Type: BACKGROUND

PMID: 11120692 (View on PubMed)

Gurfinkel EP, de la Fuente RL, Mendiz O, Mautner B. Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study. Circulation. 2002 May 7;105(18):2143-7. doi: 10.1161/01.cir.0000016182.85461.f4.

Reference Type: BACKGROUND

PMID: 11994246 (View on PubMed)

Leon de la Fuente R, Gurfinkel EP, Toledo D, Mautner B; Grupo de Estudio FLUVACS. [Flu vaccination in patients with acute coronary syndromes: treatment benefit in prespecified subgroups]. Rev Esp Cardiol. 2003 Oct;56(10):949-54. doi: 10.1016/s0300-8932(03)76991-7. Spanish.

Reference Type: BACKGROUND

PMID: 14563288 (View on PubMed)

Jackson LA, Yu O, Heckbert SR, Psaty BM, Malais D, Barlow WE, Thompson WW; Vaccine Safety Datalink Study Group. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Am J Epidemiol. 2002 Oct 1;156(7):634-40. doi: 10.1093/aje/kwf073.

Reference Type: BACKGROUND

PMID: 12244032 (View on PubMed)

Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis. 2007 Oct;7(10):658-66. doi: 10.1016/S1473-3099(07)70236-0.

Reference Type: BACKGROUND

PMID: 17897608 (View on PubMed)

Spertus JA, Winder JA, Dewhurst TA, Deyo RA, Prodzinski J, McDonell M, Fihn SD. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol. 1995 Feb;25(2):333-41. doi: 10.1016/0735-1097(94)00397-9.

Reference Type: BACKGROUND

PMID: 7829785 (View on PubMed)

Gensini GG. Coronary Angiography. Mount Kisco, NY: Futura Publishing Co; 1975.

Reference Type: BACKGROUND

Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000 Sep;36(3):959-69. doi: 10.1016/s0735-1097(00)00804-4.

Reference Type: BACKGROUND

PMID: 10987628 (View on PubMed)

Dehesh M, Gholamin S, Razavi SM, Eskandari A, Vakili H, Rahnavardi Azari M, Wang Y, Gough EK, Keshtkar-Jahromi M. Influenza Vaccination and Cardiovascular Outcomes in Patients with Coronary Artery Diseases: A Placebo-Controlled Randomized Study, IVCAD. Vaccines (Basel). 2025 Apr 27;13(5):472. doi: 10.3390/vaccines13050472.

Reference Type: DERIVED

PMID: 40432084 (View on PubMed)

Other Identifiers

SMMC- 13861008A

Identifier Type: -

Identifier Source: secondary_id

SBMU- 86-03-105-5433A

Identifier Type: -

Identifier Source: org_study_id