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Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis.

ABSTRACT: Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 ?g V710 (with or without adjuvant), 90 ?g V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a ?2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a ?2.5 GMFR in anti-IsdB antibodies compared to the baseline (P values of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis.

SUBMITTER: Moustafa M

PROVIDER: S-EPMC3428394 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis.

Moustafa Moustafa M Aronoff George R GR Chandran Chandra C Hartzel Jonathan S JS Smugar Steven S SS Galphin Claude M CM Mailloux Lionel U LU Brown Elizabeth E Dinubile Mark J MJ Kartsonis Nicholas A NA Guris Dalya D

Clinical and vaccine immunology : CVI 20120725 9

Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase I ...[more]

PMID: 22837094

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Project description:Rationale & objectiveStaphylococcus aureus (Saureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations with clinical outcomes with SAB in this population over a 21-year period.Study designProspective cohort study.Setting & participants453 hospitalized, non-neutropenic adults receiving maintenance HD who developed monomicrobial SAB between 1995 and 2015.ExposureClinical characteristics and bacterial genotype.OutcomeAll-cause and SAB-attributable mortality, persistent bacteremia, and metastatic complications.Analytical approachProportions of participants experiencing each outcome were calculated overall and by calendar year. Secular trends were estimated using binomial risk regression, a generalized linear model with the log link function for a binomial outcome. Associations with outcomes were estimated using logistic regression.ResultsOver the 21-year study period, patients receiving maintenance HD experienced significant increases in age- and diabetes-adjusted SAB-attributable mortality (0.45% [95% CI, 0.36%-0.46%] per year), persistent bacteremia (0.86% [95% CI, 0.14%-1.55%] per year), metastatic complications (0.84% [95% CI, 0.11%-1.56%] per year), and infection with the virulent Saureus clone USA300 (1.47% [95% CI, 0.33%-2.52%] per year). Over time, the suspected source of SAB was less likely to be a central venous catheter (-1.32% [95% CI, -2.05 to-0.56%] per year) or arteriovenous graft (-1.08% [95% CI, -1.54 to-0.56] per year), and more likely to be a nonvascular access source (1.89% [95% CI, 1.29%-2.43%] per year). Patients with a nonvascular access suspected source of infection were more likely to die as a result of their S aureus infection (OR, 3.20 [95% CI, 1.36-7.55]). The increase in USA300 infections may have contributed to the observed increase in persistent bacteremia (OR, 2.96 [95% CI, 1.12-7.83]) but did not explain the observed increases in SAB-attributable mortality (OR, 0.83 [95% CI, 0.19-3.61]) or metastatic complications (OR, 1.34 [95% CI, 0.53-3.41]).LimitationsSingle-center, inpatient cohort.ConclusionsThe clinical and molecular epidemiology of SAB in patients receiving maintenance HD has changed over time, with an increase in SAB-attributable mortality and morbidity despite a decline in catheter-related infections.

Project description:BackgroundPatients with end-stage renal disease on hemodialysis (ESRD-HD) and aortic stenosis have poor prognosis. The role of transcatheter aortic valve replacement (TAVR) in this high-risk population is debated.MethodsWe compared the outcomes among ESRD-HD Medicare beneficiaries who were managed with TAVR, surgical AVR (SAVR), or conservative management for aortic stenosis between 2015 and 2017, using overlap propensity score weighting analysis to control for differences in treatment assignment. The primary outcome was all-cause mortality and was compared between treatment groups as well as to age-sex matched mortality for ESRD-HD in the US population. Secondary outcomes included trend of heart failure hospitalizations.ResultsA total of 8107 ESRD-HD patients with aortic stenosis were included, 4130 (50%) underwent TAVR, 2565 (31.6%) underwent SAVR, and 1412 (17.4%) were managed conservatively. TAVR patients had more comorbidities and higher frailty compared with the other 2 groups. Thirty-day mortality was lower with TAVR compared with SAVR (4.6% versus 12.8%, P<0.01). After a median follow-up of 465 days (interquartile range, 261-759), on overlap propensity score weighting analysis, there was no difference in mortality between TAVR and SAVR (adjusted hazard ratio, 1.02 [95% CI, 0.91-1.15], P=0.7), and mortality was lower with TAVR compared with conservative management (adjusted hazard ratio, 0.53 [95% CI, 0.47-0.60], P<0.001). Standardized mortality ratios with TAVR, SAVR, and conservative management compared with age-sex matched ESRD-HD US population were 1.24, 1.27, and 1.83, respectively. The rate of heart failure admissions declined after TAVR (incidence rate ratio, 0.55 [95% CI, 0.48-0.62], P<0.001) and SAVR (incidence rate ratio, 0.76 [95% CI, 0.65-0.88], P<0.001).ConclusionsIn ESRD-HD patients with aortic stenosis, mortality was lower in the short-term with TAVR compared with SAVR but comparable in the mid-term. AVR is associated with an improvement in survival and reduction in heart failure hospitalizations compared with conservative management.

Dataset Information

Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis.

Publications

Phase IIa study of the immunogenicity and safety of the novel Staphylococcus aureus vaccine V710 in adults with end-stage renal disease receiving hemodialysis.

Similar Datasets

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