Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S--Scandinavian Starch for Severe Sepsis/Septic Shock trial): study protocol, design and rationale for a double-blinded, randomised clinical trial

Abstract

Background: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis.

Methods/design: The 6S trial will randomize 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%.

Discussion: The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed.

Trial registration: ClinicalTrials.gov: NCT00962156.

Figure 1

Screen print of the randomisation instruction generated by the web-based electronic case record form following successful screening of a patient (all inclusion criteria fulfilled, no exclusion criteria fulfilled and consent obtained). Staff at trial sites will use this instruction to call the phone-based, interactive, voice response randomisation system available around the clock at Copenhagen Trial Unit for immediate and concealed allocation of the patient to trial fluid.

Figure 2

Trial fluid chart generated by the web-based electronic case record form following successful randomisation of a patient. The fluid chart is to be used bed-side by clinical staff to ensure proper use of trial fluid and document the administration of trial fluid.

Figure 3

Screen print of the first page of the screening part of the web-based electronic case record form (eCRF) (ExpertMaker, Lund, Sweden).