Scandinavian Starch for Severe Sepsis/Septic Shock Trial

Septic Shock Clinical Trial

— 6S  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00962156
• Other study ID #: 2008-262
• Secondary ID: EudraCT no. 2009
• Status: Completed
• Phase: Phase 3
• First received: August 18, 2009
• Last updated: July 9, 2012
• Start date: December 2009
• Est. completion date: March 2012

Study information

• Verified date: July 2012
• Source: Scandinavian Critical Care Trials Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 804
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

Drug:
• 6% Hydroxyethyl starch 130/0.4
Infusion for volume expansion in the ICU
• Ringers acetate
Infusion for volume expansion in the ICU

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Gentofte Hosptial	Copenhagen
Denmark	Glostrup Hospital	Copenhagen
Denmark	Herlev Hospital	Copenhagen
Denmark	Hvidovre Hospital	Copenhagen
Denmark	Rigshospitalet	Copenhagen
Denmark	Esbjerg Hospital	Esbjerg
Denmark	Herning Hospital	Herning
Denmark	Hillerød Hospital	Hillerød
Denmark	Hjørring Hospital	Hjørring
Denmark	Holbæk Hospital	Holbæk
Denmark	Holstebro Hospital	Holstebro
Denmark	Køge Hospital	Køge
Denmark	Næstved Hospital	Næstved
Denmark	Odense University Hospital	Odense
Denmark	Slagelse Hospital	Slagelse
Denmark	Sønderborg Hospital	Sønderborg
Denmark	Vejle Hospital	Vejle
Finland	Dept of Intensive Care, Helsinki University Hospital	Helsinki
Finland	Dept. of Intensive Care, Kuopio University Hospital	Kuopio
Finland	Dept of Intensive Care, Tampere University Hospital	Tampere
Iceland	Dept. of Intensive Care, Landspitali	Reykjavik
Norway	Haukeland University Hospital	Bergen
Norway	Stavanger University Hospital	Stavanger
Norway	Intensive Care Unit, University Hospital of North Norway	Tromsø
Norway	St Olavs Hospital, Trondheim University Hospital	Trondheim

Sponsors (5)

Lead Sponsor	Collaborator
Anders Perner	B. Braun Melsungen AG, Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Denmark, University of Copenhagen

Countries where clinical trial is conducted

Denmark,  Finland,  Iceland,  Norway, 

References & Publications (2)

Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, Madsen KR, Møller MH, Elkjær JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Ander — View Citation

Perner A, Haase N, Wetterslev J, Aneman A, Tenhunen J, Guttormsen AB, Klemenzson G, Pott F, Bødker KD, Bådstøløkken PM, Bendtsen A, Søe-Jensen P, Tousi H, Bestle M, Pawlowicz M, Winding R, Bülow HH, Kancir C, Steensen M, Nielsen J, Fogh B, Madsen KR, Larsen NH, Carlsson M, Wiis J, Petersen JA, Iversen S, Schøidt O, Leivdal S, Berezowicz P, Pettilä V, Ruokonen E, Klepstad P, Karlsson S, Kaukonen M, Rutanen J, Karason S, Kjældgaard 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality or dialysis-dependency		90 days	No
Secondary	Mortality		28 days	Yes
Secondary	Mortality		6 months	No
Secondary	Mortality		1 year	No
Secondary	Severity organ failure assessment score	Excluding Glascow coma score	Day 5	Yes
Secondary	Days free of ventilation	Among survivors	90 days	No
Secondary	Days free of dialysis	Among survivors	90 days	No
Secondary	Serious adverse reactions	Severe bleeding or severe allergic reactions	Followed up until ICU discharge; consequently the time frame will vary among patients	Yes
Secondary	Need of dialysis/haemofiltration		Within 90 days	No
Secondary	Need of ventilation		Within 90 days	No
Secondary	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	No
Secondary	Hospital length of stay		90 days	No
Secondary	Coagulation analyses	At selected hospitals whole-blood and biochemical coagulation analyses constitute additional secondary endpoints	5 days	No
Secondary	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	No