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

ProCESS/ARISE/ProMISe methodology writing committee members: Sandra L. Peake and Patricia Williams for the University of Adelaide, South Australia.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.The ProCESS/ARISE/ProMISe Methodology Writing Committe