Septic Shock, Severe Sepsis
Conditions
Keywords
Sepsis, Shock, Fluid therapy, Plasma expanders
Brief summary
* By tradition hydroxyethyl starch (HES) is used to obtain fast circulatory stabilisation in critically ill. * High molecular weight HES may, however, cause acute kidney failure in patients with severe sepsis. * Now the low molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICU) and 1st choice fluid for patients with severe sepsis. * HES 130/0.4 is largely unstudied in ICU patients. * This investigator-initiated Scandinavian multicentre trial will be conducted to assess the effects of HES 130/0.4 on mortality and endstage kidney failure in patients with severe sepsis. * The trial will provide important data to all clinicians who resuscitate septic patients.
Detailed description
Fluid is the mainstay treatment in sepsis resuscitation, but the effects of different crystalloid and colloid solutions on outcome remain unknown. Previously, a high molecular weight hydroxyethyl starch, HES 200, was used, but this was found to cause acute kidney failure in patients with severe sepsis. As kidney failure is an independent risk factor for death in these patients, HES 200 is not used anymore. In stead a lower molecular weight starch, HES 130, has been developed. Presently, this is the preferred colloid in Scandinavian intensive care units (ICU), but the effects of HES 130 in ICU patients are currently unknown. The proposed Scandinavian multicentre study will be conducted to assess if HES 130 contributes to acute kidney failure in patients with severe sepsis. As HES 130 is widely used, the trial will provide important safety data to clinicians who resuscitate septic patients.
Interventions
Infusion for volume expansion in the ICU
DRUGRingers acetate
Infusion for volume expansion in the ICU
Sponsors
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
University of Copenhagen
B. Braun Melsungen AG
Anders Perner
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All adult patients who * Undergo resuscitation in the ICU * AND fulfillment within the previous 24 hours of the criteria for severe sepsis (SCCM/ACCP) * AND consent is obtainable either from the patient or by proxy (physician and/or next of kin)
Exclusion criteria
The following patients will not be evaluated for inclusion: * Age \< 18 years old * Previously randomised in the 6S trial * Allergy towards hydroxyethyl starch or malic acid * Treatment with \> 1000 ml's of any synthetic colloid within the last 24 hours prior to randomisation * Any form of renal replacement therapy * Acute burn injury \> 10% body surface area * Severe hyperkalaemia, p-K \> 6 mM * Liver or kidney transplantation during current hospital admission * Intracranial bleeding within current hospitalisation * Enrollment into another ICU trial of drugs with potential action on circulation, renal function or coagulation * Withdrawal of active therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mortality or dialysis-dependency | 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 28 days | — |
| Severity organ failure assessment score | Day 5 | Excluding Glascow coma score |
| Days free of ventilation | 90 days | Among survivors |
| Serious adverse reactions | Followed up until ICU discharge; consequently the time frame will vary among patients | Severe bleeding or severe allergic reactions |
| Need of dialysis/haemofiltration | Within 90 days | — |
| Days free of dialysis | 90 days | Among survivors |
| Kidney failure | Followed up until ICU discharge; consequently the time frame will vary among patients | Severity organ failure assessment score \> 2 in the renal component |
| Hospital length of stay | 90 days | — |
| Coagulation analyses | 5 days | At selected hospitals whole-blood and biochemical coagulation analyses constitute additional secondary endpoints |
| NGAL | 5 days | At selected trial sites will plasma and urinary NGAL be analysed at randomisation to assess the predictive value for dialyse and kidney failure |
| Need of ventilation | Within 90 days | — |
Countries
Denmark, Finland, Iceland, Norway
Outcome results
None listed