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{Shankar-Hari:2021:10.3310/eme08100,
author = {Shankar-Hari, M and Santhakumaran, S and Prevost, AT and Ward, JK and Marshall, T and Bradley, C and Calfee, CS and Delucchi, KL and Sinha, P and Matthay, MA and Hackett, J and McDowell, C and Laffey, JG and Gordon, A and OKane, CM and McAuley, DF},
doi = {10.3310/eme08100},
journal = {Efficacy and Mechanism Evaluation},
pages = {1--104},
title = {Defining phenotypes and treatment effect heterogeneity to inform acute respiratory distress syndrome and sepsis trials: secondary analyses of three RCTs},
url = {http://dx.doi.org/10.3310/eme08100},
volume = {8},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundSepsis and acute respiratory distress syndrome are two heterogeneous acute illnesses with high risk of death and for which there are many ‘statistically negative’ randomised controlled trials. We hypothesised that negative randomised controlled trials occur because of between-participant differences in response to treatment, illness manifestation (phenotype) and risk of outcomes (heterogeneity).ObjectivesTo assess (1) heterogeneity of treatment effect, which tests whether or not treatment effect varies with a patient’s pre-randomisation risk of outcome; and (2) whether or not subphenotypes explain the treatment response differences in sepsis and acute respiratory distress syndrome demonstrated in randomised controlled trials.Study populationWe performed secondary analysis of two randomised controlled trials in patients with sepsis [i.e. the Vasopressin vs Noradrenaline as Initial Therapy in Septic Shock (VANISH) trial and the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial] and one acute respiratory distress syndrome multicentre randomised controlled trial [i.e. the Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial], conducted in the UK. The VANISH trial is a 2 × 2 factorial randomised controlled trial of vasopressin (Pressyn AR®; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and hydrocortisone sodium phosphate (hereafter referred to as hydrocortisone) (EfcortesolTM; Amdipharm plc, St Helier, Jersey) compared with placebo. The LeoPARDS trial is a two-arm-parallel-group randomised controlled trial of levosimendan (Simdax®; Orion Pharma, Espoo, Finland) compared with placebo. The HARP-2 trial is a parallel-group randomised controlled trial of simvastatin compared with placebo.MethodsTo test for heterogeneity of the effect on 28-day mortality of vasopressin, hydrocortisone and levosimendan in
AU  - Shankar-Hari,M
AU  - Santhakumaran,S
AU  - Prevost,AT
AU  - Ward,JK
AU  - Marshall,T
AU  - Bradley,C
AU  - Calfee,CS
AU  - Delucchi,KL
AU  - Sinha,P
AU  - Matthay,MA
AU  - Hackett,J
AU  - McDowell,C
AU  - Laffey,JG
AU  - Gordon,A
AU  - OKane,CM
AU  - McAuley,DF
DO  - 10.3310/eme08100
EP  - 104
PY  - 2021///
SN  - 2050-4365
SP  - 1
TI  - Defining phenotypes and treatment effect heterogeneity to inform acute respiratory distress syndrome and sepsis trials: secondary analyses of three RCTs
T2  - Efficacy and Mechanism Evaluation
UR  - http://dx.doi.org/10.3310/eme08100
UR  - https://www.journalslibrary.nihr.ac.uk/eme/eme08100#/abstract
UR  - http://hdl.handle.net/10044/1/91846
VL  - 8
ER  -
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