LB-1. Efficacy and Safety of an Investigational Staphylococcus aureus Vaccine in Preventing Bacteremia and Deep Sternal Wound Infections after Cardiothoracic Surgery
Session: Oral Abstract Session: Late Breaker Symposium
Saturday, October 20, 2012: 10:30 AM
Room: SDCC 24 ABC
Background: S. aureus causes serious infections following cardiothoracic (CT) surgery.  V710 is a novel vaccine containing the conserved S. aureus iron surface determinant B (IsdB) and was immunogenic & generally well-tolerated in volunteers.  We studied preoperative vaccination to prevent serious S. aureus infections after CT surgery.

Methods: In a blinded, randomized, event-driven Phase 2b/3 study, eligible adult patients scheduled for median sternotomy within 14-60 days of entry received a single 0.5-mL injection of V710 (60 μg) or placebo.  The primary efficacy outcome was prevention of S. aureus bacteremia & deep sternal wound infection (including mediastinitis) through postoperative Day 90.  Death, S. aureus-associated, & vaccine-related serious adverse events were monitored for the duration of the study.

Results: An independent monitoring committee recommended study termination after the 2nd planned interim analysis due to safety concerns & low efficacy.  Anti-IsdB IgG titers at the time of surgery in V710 recipients were consistently higher than prevaccination baseline levels & significantly higher than in placebo recipients.  In V710 recipients, the geometric mean fold-rise [95% CI] in antibody titer with opsonophagocytic activity from baseline was 2.5 [2.2, 2.8] just prior to surgery & 1.9 [1.6, 2.2] on postoperative Day 90.  However, V710 was not more efficacious than placebo in preventing primary endpoints (22 in 3528 V710 recipients vs 27 in 3517 placebo recipients; p = 0.584).  Rates of vaccine-related serious adverse events (1 in each group) & all-cause mortality (5.7 vs 5.0 deaths per 100 person-yrs; p = 0.200) were not statistically different between groups, but V710 was associated with a higher rate of postoperative multi-organ failure than placebo (0.9 vs 0.5 events per 100 person-yrs; p=0.042).  Mortality rates in patients who developed S. aureus infections were higher among V710 than placebo recipients (24.4 vs 4.2 per 100 person-yrs; D [95% CI] = 20.2 [9.2, 35.7]).

Conclusion: Despite eliciting opsonophagocytic antibody, preoperative administration of V710 did not reduce serious S. aureus infections after CT surgery.  Postoperative multi-organ failure occurred more often in V710 than placebo recipients.  Higher mortality was observed among S. aureus-infected V710 recipients than S. aureus-infected placebo recipients.

Vance G Fowler, MD, MHS1, Keith Allen2, Edson Moreira3, Moustafa Moustafa4, Frank Isgro5, Helen Boucher, MD, FIDSA6, Ralph Corey1, Yehuda Carmeli, MD, MPH7, Robert Betts8, Jonathan Hartzel9, Tessie Mcneely9, Nicholas Kartsonis9, Dalya Guris9, Matthew Onorato9, Steven Smugar9, Mark Dinubile9 and Ajoke Sobanjo-Ter Meulen9, (1)Duke University Medical Center, Durham, NC, (2)St. Luke's Mid-America Heart and Vascular Institute, Kansas City, MO, (3)Mcgill University, Montreal, QC, Canada, (4)South Carolina Nephrology & Hypertension Center, Orangeburg, SC, (5)Academic City Hospital Ludwigshafen, Ludwigshafen, Germany, (6)Tufts New Engl Med Ctr, Boston, MA, (7)Beth Israel Deaconess Medical Center, Stamford, CT, (8)University of Rochester, Rochester, NY, (9)Merck Sharp & Dohme, Corp., Whitehouse Station, NJ

Disclosures:

V. G. Fowler, Merck: Consultant, Investigator and Scientific Advisor, Research grant, Research support and Speaker honorarium

K. Allen, Merck: Investigator, Research support

E. Moreira, Merck: Board Member and Speaker's Bureau, Educational grant and Speaker honorarium

M. Moustafa, Merck: Investigator, Research support

F. Isgro, Merck: Investigator, Research support

H. Boucher, Merck: Consultant and Investigator, Consulting fee and Research grant

R. Corey, Merck: Investigator, Research support

Y. Carmeli, Merck: Investigator, Research support

R. Betts, Merck: Investigator, Research support

J. Hartzel, Merck: Employee, Salary and stock or stock options

T. Mcneely, Merck: Employee, Salary and stock or stock options

N. Kartsonis, Merck: Employee, Salary and stock or stock options

D. Guris, Merck: Employee, Salary and stock or stock options

M. Onorato, Merck: Employee, Salary and stock or stock options

S. Smugar, Merck: Employee, Salary and stock or stock options

M. Dinubile, Merck: Employee, Salary and stock or stock options

A. Sobanjo-Ter Meulen, Merck: Employee, Salary and stock or stock options

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