Scandinavian Starch for Severe Sepsis/Septic Shock Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Hydroxyethyl Starch 130/0.4 Compared With Balanced Crystalloid Solution on Mortality and Kidney Failure in Patients With Severe Sepsis

Conditions
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Severe Sepsis, Septic Shock

Intervention / Treatment
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* Drug: 6% Hydroxyethyl starch 130/0.4
* Drug: Ringers acetate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HES 130/0.4<br>Volume expansion | Drug: 6% Hydroxyethyl starch 130/0.4<br>* Infusion for volume expansion in the ICU<br>* Other names: 6% Tetraspan;|
| Active Comparator: Ringer acetate<br>Volume expansion | Drug: Ringers acetate<br>* Infusion for volume expansion in the ICU<br>* Other names: Ringerfundin / Sterofundin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality or dialysis-dependency |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 28 days | 
| Mortality |  | 6 months | 
| Mortality |  | 1 year | 
| Severity organ failure assessment score | Excluding Glascow coma score | Day 5 | 
| Days free of ventilation | Among survivors | 90 days | 
| Days free of dialysis | Among survivors | 90 days | 
| Serious adverse reactions | Severe bleeding or severe allergic reactions | Followed up until ICU discharge; consequently the time frame will vary among patients | 
| Need of dialysis/haemofiltration |  | Within 90 days | 
| Need of ventilation |  | Within 90 days | 
| Kidney failure | Severity organ failure assessment score > 2 in the renal component | Followed up until ICU discharge; consequently the time frame will vary among patients | 
| Hospital length of stay |  | 90 days | 
| Coagulation analyses | At selected hospitals whole-blood and biochemical coagulation analyses constitute additional secondary endpoints | 5 days | 
| NGAL | At selected trial sites will plasma and urinary NGAL be analysed at randomisation to assess the predictive value for dialyse and kidney failure | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Shock, Fluid therapy, Plasma expanders