Recombinant human activated protein C for severe sepsis in neonates

Kylat, Ranjit I; Ohlsson, Arne

doi:10.1002/14651858.cd005385.pub2

Cited by 19 publications

(10 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To more fully address the latter question of whether IVIG reduces sepsis (suspected or proven) mortality, a multi-center, international, double-blind, randomized controlled clinical trial (International Neonatal Immunotherapy Study) has been completed with publication of the results anticipated in 2009. Other therapies such as activated protein C 49 and pentoxfylline 31,32 (currently being evaluated in a phase II trial as an adjunctive treatment for necrotizing enterocolitis (NEC) in premature infants [clinicaltrials.gov trial #NCT00271336]) have shown some promise, although future evaluation is warranted as their mechanisms of action are incompletely characterized and dangerous side effects (increased risk of bleeding) remain a concern with activated protein C 50 . Other potential immunomodulatory targets include reduction of oxidative stress and amino acid supplementation during periods of critical illness.…”

Section: Attempts At Neonatal Immunomodulationmentioning

confidence: 99%

Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis

et al. 2008

View full text Add to dashboard Cite

Prevention of neonatal infection-related mortality represents a significant global challenge particularly in the vulnerable premature population. The increased risk of death from sepsis is likely due to the specific immune deficits found in the neonate as compared to the adult. Stimulation of the neonatal immune system to prevent and or treat infection has been attempted in the past largely without success. In this review, we identify some of the known deficits in the neonatal immune system and their clinical impact, summarize previous attempts at immunomodulation and the outcomes of these interventions, and discuss the potential of novel immunomodulatory therapies to improve neonatal sepsis outcome.

show abstract

Section: Attempts At Neonatal Immunomodulationmentioning

confidence: 99%

Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Protein C has been studied as a potential treatment for severe neonatal sepsis using activated protein C concentrate, although there is no clear evidence of benefit. 22 Protein C levels are significantly higher in healthy controls compared with septic neonates, and protein C has been described as a useful biomarker in severe sepsis. 23 Protein C has also demonstrated prognostic utility for mortality in septic low birthweight neonates.…”

Section: Novel Pathogen-targeted Ngs Systemmentioning

confidence: 99%

Fast I(n)dentification of Pathogens in Neonates (FINDPATH-N): protocol for a prospective pilot cohort study of next-generation sequencing for pathogen identification in neonates with suspected sepsis

Klowak

Helou

Pernica

et al. 2020

bmjpo

View full text Add to dashboard Cite

IntroductionSepsis is a major source of morbidity and mortality in neonates; however, identification of the causative pathogens is challenging. Many neonates have negative blood cultures despite clinical evidence of sepsis. Next-generation sequencing (NGS) is a high-throughput, parallel sequencing technique for DNA. Pathogen-targeted enrichment followed by NGS has the potential to be more sensitive and faster than current gold-standard blood culture. In this pilot study, we will test the feasibility and pathogen detection patterns of pathogen-targeted NGS in neonates with suspected sepsis. Additionally, the distribution and diagnostic accuracy of biomarkers cell-free DNA and protein C levels at two time points will be explored.Methods and analysisWe will conduct a prospective, pilot observational study. Neonates over 1 kg with suspected sepsis from a single tertiary care children’s hospital will be recruited for the study. Recruitment will be censored at 200 events or 6 months’ duration. Two blood study samples will be taken: the first simultaneous to the blood culture (time=0 hour, for NGS and biomarkers) via an exception to consent (deferred consent) and another 24 hours later after prospective consent (biomarkers only). Neonates will be adjudicated into those with clinical sepsis, culture-proven sepsis and without sepsis based on clinical criteria. Feasibility parameters (eg, recruitment) and NGS process time will be reported.For analysis, NGS results will be described in aggregate, compared with the simultaneous blood culture (sensitivity and specificity) and reviewed via expert panel for plausibility. Pilot data for biomarker distribution and diagnostic accuracy (sensitivity and specificity) for distinguishing between septic and non-septic neonates will be reported.Ethics and disseminationEthics approval has been granted by the Hamilton Integrated Research Ethics Board. We will seek publication of study results in peer-reviewed journals.

show abstract

“…However, results among adults and children demonstrated lack of efficacy and an increased risk of bleeding associated with higher mortality rates ( 122 , 123 ). Consequently, rhAPC was withdrawn from the market before any randomized trials were performed in preterm neonates, and in 2012 a clear recommendation against the treatment with rhAPC for neonatal sepsis was proclaimed ( 124 ).…”

Section: Prior Studies That Have Not Demonstrated Clinical Benefitmentioning

confidence: 99%

Immunomodulation to Prevent or Treat Neonatal Sepsis: Past, Present, and Future

et al. 2018

View full text Add to dashboard Cite

Despite continued advances in neonatal medicine, sepsis remains a leading cause of death worldwide in neonatal intensive care units. The clinical presentation of sepsis in neonates varies markedly from that in older children and adults, and distinct acute inflammatory responses results in age-specific inflammatory and protective immune response to infection. This review first provides an overview of the neonatal immune system, then covers current mainstream, and experimental preventive and adjuvant therapies in neonatal sepsis. We also discuss how the distinct physiology of the perinatal period shapes early life immune responses and review strategies to reduce neonatal sepsis-related morbidity and mortality. A summary of studies that characterize immune ontogeny and neonatal sepsis is presented, followed by discussion of clinical trials assessing interventions such as breast milk, lactoferrin, probiotics, and pentoxifylline. Finally, we critically appraise future treatment options such as stem cell therapy, other antimicrobial protein and peptides, and targeting of pattern recognition receptors in an effort to prevent and/or treat sepsis in this highly vulnerable neonatal population.

show abstract

Recombinant human activated protein C for severe sepsis in neonates

Cited by 19 publications

References 58 publications

Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis

Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis

Fast I(n)dentification of Pathogens in Neonates (FINDPATH-N): protocol for a prospective pilot cohort study of next-generation sequencing for pathogen identification in neonates with suspected sepsis

Immunomodulation to Prevent or Treat Neonatal Sepsis: Past, Present, and Future

Contact Info

Product

Resources

About