| Title |
Pharmacogenomic biomarkers do not predict response to drotrecogin alfa in patients with severe sepsis
|
|---|---|
| Published in |
Annals of Intensive Care, January 2018
|
| DOI | 10.1186/s13613-018-0353-2 |
| Pubmed ID | |
| Authors |
Djillali Annane, Jean-Paul Mira, Lorraine B. Ware, Anthony C. Gordon, Charles J. Hinds, David C. Christiani, Jonathan Sevransky, Kathleen Barnes, Timothy G. Buchman, Patrick J. Heagerty, Robert Balshaw, Nadia Lesnikova, Karen de Nobrega, Hugh F. Wellman, Mauricio Neira, Alexandra D. J. Mancini, Keith R. Walley, James A. Russell |
| Abstract |
To 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. Patients 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. Six 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. Neither IRP A nor IRP B predicted differential response to DrotAA on in-hospital 28-day mortality. ClinicalTrials.gov registration NCT01486524. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 5 | 19% |
| Researcher | 4 | 15% |
| Student > Doctoral Student | 3 | 12% |
| Student > Master | 3 | 12% |
| Professor | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 8 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 27% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Agricultural and Biological Sciences | 2 | 8% |
| Computer Science | 2 | 8% |
| Nursing and Health Professions | 1 | 4% |
| Other | 5 | 19% |
| Unknown | 7 | 27% |
Attention Score in Context
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#15,490,822
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Outputs from Annals of Intensive Care
#834
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Outputs of similar age from Annals of Intensive Care
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