Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe

Intensive Care Med. 2013 Oct;39(10):1760-75. doi: 10.1007/s00134-013-3024-7. Epub 2013 Aug 30.


Purpose: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australasia
  • Data Interpretation, Statistical
  • Emergency Service, Hospital / standards
  • Hospital Mortality
  • Humans
  • International Cooperation
  • Multicenter Studies as Topic / methods*
  • Multicenter Studies as Topic / standards
  • Randomized Controlled Trials as Topic / methods*
  • Randomized Controlled Trials as Topic / standards
  • Research Design
  • Resuscitation / methods*
  • Shock, Septic / mortality
  • Shock, Septic / therapy*
  • Systemic Inflammatory Response Syndrome / mortality
  • Systemic Inflammatory Response Syndrome / therapy*
  • Time-to-Treatment
  • United Kingdom
  • United States