Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8722
Title: Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial.
Authors: Fowler Junior, Vance G.
Allen, Keith B.
Moreira Júnior, Edson Duarte
Moustafa, Moustafa
Isgro, Frank
Boucher, Helen W.
Corey, G. Ralph
Carmeli, Yehuda
Betts, Robert
Hartzel, Jonathan S.
Chan, Ivan S. F.
McNeely, Tessie B.
Kartsonis, Nicholas A.
Guris, Dalya
Onorato, Matthew T.
Smugar, Steven S.
DiNubile, Mark J.
Meulen, Ajoke Sobanjo-ter
Affilliation: Duke University Medical Center. Durham, North Carolina / Duke Clinical Research Institute. Durham, North Carolina
St Luke’s Mid-America Heart and Vascular Institute. Kansas City, Missouri
Associacão Obras Sociais Irmã Dulce. Salvador, Bahia, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
South Carolina Nephrology and Hypertension Center. Orangeburg
Academic City Hospital Ludwigshafen. Ludwigshafen, Germany
Tufts Medical Center. Boston, Massachusetts
Duke University Medical Center. Durham, North Carolina / Duke Clinical Research Institute. Durham, North Carolina
Beth Israel Deaconess Medical. Boston, Massachusetts
University of Rochester School of Medicine. Rochester, New York
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Merck Sharp & Dohme, Whitehouse Station. New Jersey, NJ
Abstract: IMPORTANCE: Infections due to Staphylococcus aureus are serious complications of cardiothoracic surgery. A novel vaccine candidate (V710) containing the highly conserved S. aureus iron surface determinant B is immunogenic and generally well tolerated in volunteers. OBJECTIVE: To evaluate the efficacy and safety of preoperative vaccination in preventing serious postoperative S. aureus infection in patients undergoing cardiothoracic surgery. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, event-driven trial conducted between December 2007 and August 2011 among 8031 patients aged 18 years or older who were scheduled for full median sternotomy within 14 to 60 days of vaccination at 165 sites in 26 countries. INTERVENTION: Participants were randomly assigned to receive a single 0.5-mL intramuscular injection of either V710 vaccine, 60 µg (n = 4015), or placebo (n = 4016). MAIN OUTCOME MEASURES: The primary efficacy end point was prevention of S. aureus bacteremia and/or deep sternal wound infection (including mediastinitis) through postoperative day 90. Secondary end points included all S. aureus surgical site and invasive infections through postoperative day 90. Three interim analyses with futility assessments were planned. RESULTS: The independent data monitoring committee recommended termination of the study after the second interim analysis because of safety concerns and low efficacy. At the end of the study, the V710 vaccine was not significantly more efficacious than placebo in preventing either the primary end points (22/3528 V710 vaccine recipients [2.6 per 100 person-years] vs 27/3517 placebo recipients [3.2 per 100 person-years]; relative risk, 0.81; 95% CI, 0.44-1.48; P = .58) or secondary end points despite eliciting robust antibody responses. Compared with placebo, the V710 vaccine was associated with more adverse experiences during the first 14 days after vaccination (1219/3958 vaccine recipients [30.8%; 95% CI, 29.4%-32.3%] and 866/3967 placebo recipients [21.8%; 95% CI, 20.6%-23.1%], including 797 [20.1%; 95% CI, 18.9%-21.4%] and 378 [9.5%; 95% CI, 8.6%-10.5%] with injection site reactions and 66 [1.7%; 95% CI, 1.3%-2.1%] and 51 [1.3%; 95% CI, 1.0%-1.7%] with serious adverse events, respectively) and a significantly higher rate of multiorgan failure during the entire study (31 vs 17 events; 0.9 [95% CI, 0.6-1.2] vs 0.5 [95% CI, 0.3-0.8] events per 100 person-years; P = .04). Although the overall incidence of vaccine-related serious adverse events (1 in each group) and the all-cause mortality rate (201/3958 vs 177/3967; 5.7 [95% CI, 4.9-6.5] vs 5.0 [95% CI, 4.3-5.7] deaths per 100 person-years; P = .20) were not statistically different between groups, the mortality rate in patients with staphylococcal infections was significantly higher among V710 vaccine than placebo recipients (15/73 vs 4/96; 23.0 [95% CI, 12.9-37.9] vs 4.2 [95% CI, 1.2-10.8] per 100 person-years; difference, 18.8 [95% CI, 8.0-34.1] per 100 person-years). CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiothoracic surgery with median sternotomy, the use of a vaccine against S. aureus compared with placebo did not reduce the rate of serious postoperative S. aureus infections and was associated with increased mortality among patients who developed S. aureus infections. These findings do not support the use of the V710 vaccine for patients undergoing surgical interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00518687
DeCS: Bacteriemia/prevenção & controle
Infecções Estafilocócicas/prevenção & controle
Vacinas Antiestafilocócicas/administração & dosagem
Vacinas Antiestafilocócicas/efeitos adversos
Esternotomia/efeitos adversos
Infecção da Ferida Operatória/prevenção & controle
Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Bacteriemia/mortalidade
Procedimentos Cirúrgicos Cardiovasculares
Método Duplo-Cego
Feminino
Humanos
Masculino
Meia-Idade
Infecções Estafilocócicas/mortalidade
Staphylococcus aureus
Procedimentos Cirúrgicos Torácicos/efeitos adversos
Vacinação
Adulto Jovem
Issue Date: 2013
Publisher: American Medical Association
Citation: FOWLER, V. G. et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA, v.309, n.13, p.1368-1378, 2013.
ISSN: 1538-3598
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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