Imperial College London
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Professor Anthony Gordon

Faculty of Medicine, Department of Surgery & Cancer

Chair in Anaesthesia and Critical Care
 
 
 
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Contact

 

anthony.gordon

 
 
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Location

 

ICUQueen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Annane:2018:10.1186/s13613-018-0353-2,
author = {Annane, D and Mira, J-P and Ware, LB and Gordon, AC and HInds, CJ and Christiani, DC and Sevransky, J and Barnes, K and Buchman, TG and Heagerty, PJ and Balshaw, R and Lesnikova, N and de, Nobrega K and Wellman, HF and Neira, M and Mancini, ADJ and Walley, KR and Russell, JA},
doi = {10.1186/s13613-018-0353-2},
journal = {Annals of Intensive Care},
pages = {1--11},
title = {Pharmacogenomic biomarkers do not predict response to drotrecogin alfa in patients with severe sepsis},
url = {http://dx.doi.org/10.1186/s13613-018-0353-2},
volume = {8},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PurposeTo explore potential design for pharmacogenomics trials in sepsis, we investigate the interaction between pharmacogenomic biomarkers and response to drotrecogin alfa (activated) (DrotAA). This trial was designed to validate whether previously identified improved response polymorphisms (IRPs A and B) were associated with an improved response to DrotAA in severe sepsis.MethodsPatients with severe sepsis at high risk of death, who received DrotAA or not, with DNA available were included and matched to controls adjusting for age, APACHE II or SAPS II, organ dysfunction, ventilation, medical/surgical status, infection site, and propensity score (probability that a patient would have received DrotAA given their baseline characteristics). Independent genotyping and two-phase data transfer mitigated bias. The primary analysis compared the effect of DrotAA in IRP+ and IRP− groups on in-hospital 28-day mortality. Secondary endpoints included time to death in hospital; intensive care unit (ICU)-, hospital-, and ventilator-free days; and overall DrotAA treatment effect on mortality.ResultsSix hundred and ninety-two patients treated with DrotAA were successfully matched to 1935 patients not treated with DrotAA. Genotyping was successful for 639 (DrotAA) and 1684 (nonDrotAA) matched patients. The primary hypothesis of a genotype-by-treatment interaction (assessed by conditional logistic regression analysis) was not significant (P = 0.30 IRP A; P = 0.78 IRP B), and there was no significant genotype by treatment interaction for any secondary endpoint.ConclusionsNeither IRP A nor IRP B predicted differential response to DrotAA on in-hospital 28-day mortality.
AU  - Annane,D
AU  - Mira,J-P
AU  - Ware,LB
AU  - Gordon,AC
AU  - HInds,CJ
AU  - Christiani,DC
AU  - Sevransky,J
AU  - Barnes,K
AU  - Buchman,TG
AU  - Heagerty,PJ
AU  - Balshaw,R
AU  - Lesnikova,N
AU  - de,Nobrega K
AU  - Wellman,HF
AU  - Neira,M
AU  - Mancini,ADJ
AU  - Walley,KR
AU  - Russell,JA
DO  - 10.1186/s13613-018-0353-2
EP  - 11
PY  - 2018///
SN  - 2110-5820
SP  - 1
TI  - Pharmacogenomic biomarkers do not predict response to drotrecogin alfa in patients with severe sepsis
T2  - Annals of Intensive Care
UR  - http://dx.doi.org/10.1186/s13613-018-0353-2
UR  - http://hdl.handle.net/10044/1/56667
VL  - 8
ER  -
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