Clinical trial NCT00962156: Scandinavian Starch for Severe Sepsis/Septic Shock Trial
Official title: Effects of Hydroxyethyl Starch 130/0.4 Compared With Balanced Crystalloid Solution on Mortality and Kidney Failure in Patients With Severe Sepsis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Sepsis
Septic Shock
Keywords: Sepsis
Shock
Fluid therapy
Plasma expanders
Lead sponsor: Scandinavian Critical Care Trials Group
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: University of Copenhagen
name: B. Braun Melsungen AG
First posted: 2009-08-19
Enrollment: 804
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mortality or dialysis-dependency
timeFrame: 90 days
Secondary outcomes:
measure: Mortality
timeFrame: 28 days
measure: Mortality
timeFrame: 6 months
measure: Mortality
timeFrame: 1 year
measure: Severity organ failure assessment score
timeFrame: Day 5
measure: Days free of ventilation
timeFrame: 90 days
measure: Days free of dialysis
timeFrame: 90 days
measure: Serious adverse reactions
timeFrame: Followed up until ICU discharge; consequently the time frame will vary among patients
measure: Need of dialysis/haemofiltration
timeFrame: Within 90 days
measure: Need of ventilation
timeFrame: Within 90 days
measure: Kidney failure
timeFrame: Followed up until ICU discharge; consequently the time frame will vary among patients
measure: Hospital length of stay
timeFrame: 90 days
measure: Coagulation analyses
timeFrame: 5 days
measure: NGAL
timeFrame: 5 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Gentofte Hosptial
city: Copenhagen
country: Denmark
facility: Glostrup Hospital
city: Copenhagen
country: Denmark
facility: Herlev Hospital
city: Copenhagen
country: Denmark
facility: Hvidovre Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Esbjerg
country: Denmark
facility: Esbjerg Hospital
city: Herning
country: Denmark
facility: Herning Hospital
city: Hillerød
country: Denmark
facility: Hillerød Hospital
city: Hjørring
country: Denmark
facility: Hjørring Hospital
city: Holbæk
country: Denmark
facility: Holbæk Hospital
city: Holstebro
country: Denmark
facility: Holstebro Hospital
city: Køge
country: Denmark
facility: Køge Hospital
city: Næstved
country: Denmark
facility: Næstved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Slagelse
country: Denmark
facility: Slagelse Hospital
city: Sønderborg
country: Denmark
facility: Sønderborg Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Helsinki
country: Finland
facility: Dept of Intensive Care, Helsinki University Hospital
city: Kuopio
country: Finland
facility: Dept. of Intensive Care, Kuopio University Hospital
city: Tampere
country: Finland
facility: Dept of Intensive Care, Tampere University Hospital
city: Reykjavik
country: Iceland
facility: Dept. of Intensive Care, Landspitali
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: Intensive Care Unit, University Hospital of North Norway
city: Trondheim
country: Norway
facility: St Olavs Hospital, Trondheim University Hospital
Study officials:
affiliation: ICU, Rigshospitalet, University of Copenhagen
name: Anders Perner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Nicolai Haase, MD
role: STUDY_DIRECTOR
References:
citation: Perner A, Haase N, Wetterslev J, Aneman A, Tenhunen J, Guttormsen AB, Klemenzson G, Pott F, Bodker KD, Badstolokken PM, Bendtsen A, Soe-Jensen P, Tousi H, Bestle M, Pawlowicz M, Winding R, Bulow HH, Kancir C, Steensen M, Nielsen J, Fogh B, Madsen KR, Larsen NH, Carlsson M, Wiis J, Petersen JA, Iversen S, Schoidt O, Leivdal S, Berezowicz P, Pettila V, Ruokonen E, Klepstad P, Karlsson S, Kaukonen M, Rutanen J, Karason S, Kjaeldgaard AL, Holst LB, Wernerman J; Scandinavian Critical Care Trials Group. 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. Trials. 2011 Jan 27;12:24. doi: 10.1186/1745-6215-12-24.
citation: Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman A, Madsen KR, Moller MH, Elkjaer JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Soe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjaeldgaard AL, Fabritius ML, Mondrup F, Pott FC, Moller TP, Winkel P, Wetterslev J; 6S Trial Group; Scandinavian Critical Care Trials Group. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012 Jul 12;367(2):124-34. doi: 10.1056/NEJMoa1204242. Epub 2012 Jun 27.
citation: Ostrowski SR, Haase N, Muller RB, Moller MH, Pott FC, Perner A, Johansson PI. Association between biomarkers of endothelial injury and hypocoagulability in patients with severe sepsis: a prospective study. Crit Care. 2015 Apr 24;19(1):191. doi: 10.1186/s13054-015-0918-5.
citation: Perner A, Haase N, Winkel P, Guttormsen AB, Tenhunen J, Klemenzson G, Muller RG, Aneman A, Wetterslev J. Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer's acetate. Intensive Care Med. 2014 Jul;40(7):927-34. doi: 10.1007/s00134-014-3311-y. Epub 2014 May 8.
citation: Muller RG, Haase N, Wetterslev J, Perner A. Effects of hydroxyethyl starch in subgroups of patients with severe sepsis: exploratory post-hoc analyses of a randomised trial. Intensive Care Med. 2013 Nov;39(11):1963-71. doi: 10.1007/s00134-013-3090-x. Epub 2013 Sep 14.