title: Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe.
abstract: OBJECTIVE
  To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock.
  
  
  METHODS
  We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences.
  
  
  RESULTS
  All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS.
  
  
  CONCLUSIONS
  Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials.
authors: David T
authors: DT
authors: Huang
authors: Derek C
authors: DC
authors: Angus
authors: Amber
authors: A
authors: Barnato
authors: Scott R
authors: SR
authors: Gunn
authors: John A
authors: JA
authors: Kellum
authors: Diana K
authors: DK
authors: Stapleton
authors: Lisa A
authors: LA
authors: Weissfeld
authors: Donald M
authors: DM
authors: Yealy
authors: Sandra L
authors: SL
authors: Peake
authors: Anthony
authors: A
authors: Delaney
authors: Rinaldo
authors: R
authors: Bellomo
authors: Peter
authors: P
authors: Cameron
authors: Alisa
authors: A
authors: Higgins
authors: Anna
authors: A
authors: Holdgate
authors: Belinda
authors: B
authors: Howe
authors: Steven A
authors: SA
authors: Webb
authors: Patricia
authors: P
authors: Williams
authors: Tiffany M
authors: TM
authors: Osborn
authors: Paul R
authors: PR
authors: Mouncey
authors: David A
authors: DA
authors: Harrison
authors: Sheila E
authors: SE
authors: Harvey
authors: Kathryn M
authors: KM
authors: Rowan
mesh_terms: D000328:Adult; D044362:Australasia; D003627:Data Interpretation, Statistical; D004636:Emergency Service, Hospital / Q000592:standards; D017052:Hospital Mortality; D006801:Humans; D007391:International Cooperation; D015337:Multicenter Studies as Topic / Q000379:methods* / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards; D012107:Research Design; D012151:Resuscitation / Q000379:methods*; D012772:Shock, Septic / Q000401:mortality / Q000628:therapy*; D018746:Systemic Inflammatory Response Syndrome / Q000401:mortality / Q000628:therapy*; D061665:Time-to-Treatment; D006113:United Kingdom; D014481:United States
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