Influenza Vaccine To Prevent Adverse Vascular Events:Pilot

Summary

A multi-centre, randomized, placebo controlled, trial. Participants at high-risk for vascular events from the network of INTER- CHF will be randomized to inactivated influenza vaccine or placebo and followed prospectively over three influenza seasons. 600 participants will be enrolled prior to influenza season and randomized to either influenza vaccine or saline placebo.

Timeline

Start

2015-04

Primary completion

2015-12

Completion

2015-12

Publications

• Background DataFax - Data Management Software for Clinical Trials. http://www.datafax.com/; accessed February 15, 2013.
• Background Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6.
• Background ACCORD Study Group; Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14.
• Background ACCORD Study Group; Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr, Cushman WC, Simons-Morton DG, Byington RP. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1563-74. doi: 10.1056/NEJMoa1001282. Epub 2010 Mar 14.
• Background CURRENT-OASIS 7 Investigators; Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010 Sep 2;363(10):930-42. doi: 10.1056/NEJMoa0909475.
• Background ACCORD Study Group; Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH Jr, Byington RP, Rosenberg YD, Friedewald WT. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011 Mar 3;364(9):818-28. doi: 10.1056/NEJMoa1006524.
• Background ORIGIN Trial Investigators; Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012 Jul 26;367(4):309-18. doi: 10.1056/NEJMoa1203859. Epub 2012 Jun 11.
• Background ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
• Background Ontario Case Costing Initiative. Toronto, Ontario: Ontario Ministry of Health and Long-term Care, 2005. (Accessed January 29, 2011 at http://www.occp.com).
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• Background Call SA, Vollenweider MA, Hornung CA, Simel DL, McKinney WP. Does this patient have influenza? JAMA. 2005 Feb 23;293(8):987-97. doi: 10.1001/jama.293.8.987.
• Background Einhorn PT, Davis BR, Massie BM, Cushman WC, Piller LB, Simpson LM, Levy D, Nwachuku CE, Black HR; ALLHAT Collaborative Research Group. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Heart Failure Validation Study: diagnosis and prognosis. Am Heart J. 2007 Jan;153(1):42-53. doi: 10.1016/j.ahj.2006.10.012.
• Background Granger CB, Vogel V, Cummings SR, Held P, Fiedorek F, Lawrence M, Neal B, Reidies H, Santarelli L, Schroyer R, Stockbridge NL, Feng Zhao. Do we need to adjudicate major clinical events? Clin Trials. 2008;5(1):56-60. doi: 10.1177/1740774507087972.
• Background Pogue J, Walter SD, Yusuf S. Evaluating the benefit of event adjudication of cardiovascular outcomes in large simple RCTs. Clin Trials. 2009 Jun;6(3):239-51. doi: 10.1177/1740774509105223.
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• Background Canadian Community Health Survey: influenza immunization coverage results. http://www.bccdc.ca/imm-vac/BCImmunizationCov/flucoverage/default.htm.
• Background Mereckiene J, Cotter S, Nicoll A, Levy-Bruhl D, Ferro A, Tridente G, Zanoni G, Berra P, Salmaso S, O'Flanagan D, O Flanagan D; VENICE Project Gatekeepers Group. National seasonal influenza vaccination survey in Europe, 2008. Euro Surveill. 2008 Oct 23;13(43):19017. doi: 10.2807/ese.13.43.19017-en.
• Background Blank PR, Schwenkglenks M, Szucs TD. Disparities in influenza vaccination coverage rates by target group in five European countries: trends over seven consecutive seasons. Infection. 2009 Oct;37(5):390-400. doi: 10.1007/s15010-009-8467-y. Epub 2009 Sep 18.
• Background Centers for Disease Control and Prevention (CDC). Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP)--United States, 2012-13 influenza season. MMWR Morb Mortal Wkly Rep. 2012 Aug 17;61(32):613-8.
• Background STATEMENT ON SEASONAL INFLUENZA VACCINE FOR 2012-2013: An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI). Can Commun Dis Rep. 2012 Aug 1;38(ACS-2):1-36. doi: 10.14745/ccdr.v38i00a02. eCollection 2012 Aug 1. No abstract available.
• Background Natarajan P, Cannon CP. Myocardial infarction vaccine? Evidence supporting the influenza vaccine for secondary prevention. Eur Heart J. 2011 Jul;32(14):1701-3. doi: 10.1093/eurheartj/ehr053. Epub 2011 Mar 15. No abstract available.
• Background Phrommintikul A, Kuanprasert S, Wongcharoen W, Kanjanavanit R, Chaiwarith R, Sukonthasarn A. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J. 2011 Jul;32(14):1730-5. doi: 10.1093/eurheartj/ehr004. Epub 2011 Feb 2.
• Background Ciszewski A, Bilinska ZT, Brydak LB, Kepka C, Kruk M, Romanowska M, Ksiezycka E, Przyluski J, Piotrowski W, Maczynska R, Ruzyllo W. Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study. Eur Heart J. 2008 Jun;29(11):1350-8. doi: 10.1093/eurheartj/ehm581. Epub 2008 Jan 10.
• Background Gurfinkel EP, Leon de la Fuente R, Mendiz O, Mautner B. Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study. Eur Heart J. 2004 Jan;25(1):25-31. doi: 10.1016/j.ehj.2003.10.018.
• Background Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis. 2009 Oct;9(10):601-10. doi: 10.1016/S1473-3099(09)70233-6.
• Background Keller T, Weeda VB, van Dongen CJ, Levi M. Influenza vaccines for preventing coronary heart disease. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD005050. doi: 10.1002/14651858.CD005050.pub2.
• Background Population Health Research Institute http://www.phri.ca/
• Background Jackson LA, Nelson JC, Benson P, Neuzil KM, Reid RJ, Psaty BM, Heckbert SR, Larson EB, Weiss NS. Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors. Int J Epidemiol. 2006 Apr;35(2):345-52. doi: 10.1093/ije/dyi275. Epub 2005 Dec 20.
• Background Jackson LA, Jackson ML, Nelson JC, Neuzil KM, Weiss NS. Evidence of bias in estimates of influenza vaccine effectiveness in seniors. Int J Epidemiol. 2006 Apr;35(2):337-44. doi: 10.1093/ije/dyi274. Epub 2005 Dec 20.
• Background Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators; Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008 Sep 27;372(9644):1174-83. doi: 10.1016/S0140-6736(08)61242-8. Epub 2008 Aug 29.
• Background ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008 Apr 10;358(15):1547-59. doi: 10.1056/NEJMoa0801317. Epub 2008 Mar 31.
• Background Teo K, Yusuf S, Sleight P, Anderson C, Mookadam F, Ramos B, Hilbrich L, Pogue J, Schumacher H; ONTARGET/TRANSCEND Investigators. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J. 2004 Jul;148(1):52-61. doi: 10.1016/j.ahj.2004.03.020.
• Background Johnstone J, Loeb M, Teo KK, Gao P, Dyal L, Liu L, Avezum A, Cardona-Munoz E, Sleight P, Fagard R, Yusuf S; Ongoing Telmisartan Alone and in Combination With Ramipril Global EndPoint Trial (ONTARGET); Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) Investigators. Influenza vaccination and major adverse vascular events in high-risk patients. Circulation. 2012 Jul 17;126(3):278-86. doi: 10.1161/CIRCULATIONAHA.111.071100. Epub 2012 Jun 19.
• Background Wang CS, Wang ST, Lai CT, Lin LJ, Chou P. Impact of influenza vaccination on major cause-specific mortality. Vaccine. 2007 Jan 26;25(7):1196-203. doi: 10.1016/j.vaccine.2006.10.015. Epub 2006 Oct 25.
• Background Armstrong BG, Mangtani P, Fletcher A, Kovats S, McMichael A, Pattenden S, Wilkinson P. Effect of influenza vaccination on excess deaths occurring during periods of high circulation of influenza: cohort study in elderly people. BMJ. 2004 Sep 18;329(7467):660. doi: 10.1136/bmj.38198.594109.AE. Epub 2004 Aug 15.
• Background 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.
• Background Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med. 2003 Apr 3;348(14):1322-32. doi: 10.1056/NEJMoa025028.
• Background Heffelfinger JD, Heckbert SR, Psaty BM, Weiss NS, Thompson WW, Bridges CB, Jackson LA. Influenza vaccination and risk of incident myocardial infarction. Hum Vaccin. 2006 Jul-Aug;2(4):161-6. doi: 10.4161/hv.2.4.2943. Epub 2006 Jul 24.
• Background Siriwardena AN, Gwini SM, Coupland CA. Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case-control study. CMAJ. 2010 Oct 19;182(15):1617-23. doi: 10.1503/cmaj.091891. Epub 2010 Sep 20.
• Background Siscovick DS, Raghunathan TE, Lin D, Weinmann S, Arbogast P, Lemaitre RN, Psaty BM, Alexander R, Cobb LA. Influenza vaccination and the risk of primary cardiac arrest. Am J Epidemiol. 2000 Oct 1;152(7):674-7. doi: 10.1093/aje/152.7.674.
• Background Lavallee P, Perchaud V, Gautier-Bertrand M, Grabli D, Amarenco P. Association between influenza vaccination and reduced risk of brain infarction. Stroke. 2002 Feb;33(2):513-8. doi: 10.1161/hs0202.102328.
• Background Meyers D, Beahm D, Jurisich P, Milford C, Edlavich S. Influenza and pneumococcal vaccinations fail to prevent myocardial infarction. Heart Drug. 2004;4:96 -100.
• Background Remme WJ, Torp-Pedersen C, Cleland JG, Poole-Wilson PA, Metra M, Komajda M, Swedberg K, Di Lenarda A, Spark P, Scherhag A, Moullet C, Lukas MA. Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET. J Am Coll Cardiol. 2007 Mar 6;49(9):963-71. doi: 10.1016/j.jacc.2006.10.059. Epub 2007 Feb 20.
• Background 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.
• Background Gwini SM, Coupland CA, Siriwardena AN. The effect of influenza vaccination on risk of acute myocardial infarction: self-controlled case-series study. Vaccine. 2011 Feb 1;29(6):1145-9. doi: 10.1016/j.vaccine.2010.12.017. Epub 2010 Dec 18.
• Background Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999 Jul;34(1):146-54. doi: 10.1016/s0735-1097(99)00168-0.
• Background Lundman P, Eriksson M, Schenck-Gustafsson K, Karpe F, Tornvall P. Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease. Circulation. 1997 Nov 18;96(10):3266-8. doi: 10.1161/01.cir.96.10.3266.
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• Background Wanishsawad C, Zhou YF, Epstein SE. Chlamydia pneumoniae-induced transactivation of the major immediate early promoter of cytomegalovirus: potential synergy of infectious agents in the pathogenesis of atherosclerosis. J Infect Dis. 2000 Feb;181(2):787-90. doi: 10.1086/315235.
• Background Davies MJ. The composition of coronary-artery plaques. N Engl J Med. 1997 May 1;336(18):1312-4. doi: 10.1056/NEJM199705013361809. No abstract available.
• Background Chan NN, Colhoun HM, Vallance P. Cardiovascular risk factors as determinants of endothelium-dependent and endothelium-independent vascular reactivity in the general population. J Am Coll Cardiol. 2001 Dec;38(7):1814-20. doi: 10.1016/s0735-1097(01)01669-2.
• Background Gheorghiade M, Bohm M, Greene SJ, Fonarow GC, Lewis EF, Zannad F, Solomon SD, Baschiera F, Botha J, Hua TA, Gimpelewicz CR, Jaumont X, Lesogor A, Maggioni AP; ASTRONAUT Investigators and Coordinators. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA. 2013 Mar 20;309(11):1125-35. doi: 10.1001/jama.2013.1954.
• Background Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A; I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 Dec 4;359(23):2456-67. doi: 10.1056/NEJMoa0805450. Epub 2008 Nov 11.
• Background Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.
• Background Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69. doi: 10.1056/NEJMoa1202299. Epub 2012 May 2.
• Background Warren-Gash C, Hayward AC, Hemingway H, Denaxas S, Thomas SL, Timmis AD, Whitaker H, Smeeth L. Influenza infection and risk of acute myocardial infarction in England and Wales: a CALIBER self-controlled case series study. J Infect Dis. 2012 Dec 1;206(11):1652-9. doi: 10.1093/infdis/jis597. Epub 2012 Oct 9.
• Background Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004 Dec 16;351(25):2611-8. doi: 10.1056/NEJMoa041747.
• Background Pesonen E, Andsberg E, Grubb A, Rautelin H, Meri S, Persson K, Puolakkainen M, Sarna S, Ohlin H. Elevated infection parameters and infection symptoms predict an acute coronary event. Ther Adv Cardiovasc Dis. 2008 Dec;2(6):419-24. doi: 10.1177/1753944708098695.
• Background Guan XR, Li X, Xin XM, Jiang LX, Cui LY, Wang LF, Li HY. Influenza virus infection and risk of acute myocardial infarction. Inflammation. 2008 Aug;31(4):266-72. doi: 10.1007/s10753-008-9074-2.
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• Background Tracking Heart Disease and Stroke in Canada. Released June 2009.
• Background Statistics Canada. Morality, Summary List of Causes 2008. Released October 18, 2011.
• Background Causes of death 2008, World Health Organization, Geneva, http://www.who.int/healthinfo/ global_burden_disease/ cod_2008_sources_methods.pdf.

Drugs

Indications