search
Back to results

Scandinavian Starch for Severe Sepsis/Septic Shock Trial (6S)

Primary Purpose

Severe Sepsis, Septic Shock

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
6% Hydroxyethyl starch 130/0.4
Ringers acetate
Sponsored by
Anders Perner
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Sepsis focused on measuring Sepsis, Shock, Fluid therapy, Plasma expanders

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Bispebjerg Hospital
  • Gentofte Hosptial
  • Glostrup Hospital
  • Herlev Hospital
  • Hvidovre Hospital
  • Rigshospitalet
  • Esbjerg Hospital
  • Herning Hospital
  • Hillerød Hospital
  • Hjørring Hospital
  • Holbæk Hospital
  • Holstebro Hospital
  • Køge Hospital
  • Næstved Hospital
  • Odense University Hospital
  • Slagelse Hospital
  • Sønderborg Hospital
  • Vejle Hospital
  • Dept of Intensive Care, Helsinki University Hospital
  • Dept. of Intensive Care, Kuopio University Hospital
  • Dept of Intensive Care, Tampere University Hospital
  • Dept. of Intensive Care, Landspitali
  • Haukeland University Hospital
  • Stavanger University Hospital
  • Intensive Care Unit, University Hospital of North Norway
  • St Olavs Hospital, Trondheim University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HES 130/0.4

Ringer acetate

Arm Description

Volume expansion

Volume expansion

Outcomes

Primary Outcome Measures

Mortality or dialysis-dependency

Secondary Outcome Measures

Mortality
Mortality
Mortality
Severity organ failure assessment score
Excluding Glascow coma score
Days free of ventilation
Among survivors
Days free of dialysis
Among survivors
Serious adverse reactions
Severe bleeding or severe allergic reactions
Need of dialysis/haemofiltration
Need of ventilation
Kidney failure
Severity organ failure assessment score > 2 in the renal component
Hospital length of stay
Coagulation analyses
At selected hospitals whole-blood and biochemical coagulation analyses constitute additional secondary endpoints
NGAL
At selected trial sites will plasma and urinary NGAL be analysed at randomisation to assess the predictive value for dialyse and kidney failure

Full Information

First Posted
August 18, 2009
Last Updated
July 9, 2012
Sponsor
Anders Perner
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research, University of Copenhagen, B. Braun Melsungen AG
search

1. Study Identification

Unique Protocol Identification Number
NCT00962156
Brief Title
Scandinavian Starch for Severe Sepsis/Septic Shock Trial
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anders Perner
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research, University of Copenhagen, B. Braun Melsungen AG

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Septic Shock
Keywords
Sepsis, Shock, Fluid therapy, Plasma expanders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
804 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HES 130/0.4
Arm Type
Experimental
Arm Description
Volume expansion
Arm Title
Ringer acetate
Arm Type
Active Comparator
Arm Description
Volume expansion
Intervention Type
Drug
Intervention Name(s)
6% Hydroxyethyl starch 130/0.4
Other Intervention Name(s)
6% Tetraspan
Intervention Description
Infusion for volume expansion in the ICU
Intervention Type
Drug
Intervention Name(s)
Ringers acetate
Other Intervention Name(s)
Ringerfundin / Sterofundin
Intervention Description
Infusion for volume expansion in the ICU
Primary Outcome Measure Information:
Title
Mortality or dialysis-dependency
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Mortality
Time Frame
28 days
Title
Mortality
Time Frame
6 months
Title
Mortality
Time Frame
1 year
Title
Severity organ failure assessment score
Description
Excluding Glascow coma score
Time Frame
Day 5
Title
Days free of ventilation
Description
Among survivors
Time Frame
90 days
Title
Days free of dialysis
Description
Among survivors
Time Frame
90 days
Title
Serious adverse reactions
Description
Severe bleeding or severe allergic reactions
Time Frame
Followed up until ICU discharge; consequently the time frame will vary among patients
Title
Need of dialysis/haemofiltration
Time Frame
Within 90 days
Title
Need of ventilation
Time Frame
Within 90 days
Title
Kidney failure
Description
Severity organ failure assessment score > 2 in the renal component
Time Frame
Followed up until ICU discharge; consequently the time frame will vary among patients
Title
Hospital length of stay
Time Frame
90 days
Title
Coagulation analyses
Description
At selected hospitals whole-blood and biochemical coagulation analyses constitute additional secondary endpoints
Time Frame
5 days
Title
NGAL
Description
At selected trial sites will plasma and urinary NGAL be analysed at randomisation to assess the predictive value for dialyse and kidney failure
Time Frame
5 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Perner, MD, PhD
Organizational Affiliation
ICU, Rigshospitalet, University of Copenhagen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nicolai Haase, MD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Study Director
Facility Information:
Facility Name
Bispebjerg Hospital
City
Copenhagen
Country
Denmark
Facility Name
Gentofte Hosptial
City
Copenhagen
Country
Denmark
Facility Name
Glostrup Hospital
City
Copenhagen
Country
Denmark
Facility Name
Herlev Hospital
City
Copenhagen
Country
Denmark
Facility Name
Hvidovre Hospital
City
Copenhagen
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Esbjerg Hospital
City
Esbjerg
Country
Denmark
Facility Name
Herning Hospital
City
Herning
Country
Denmark
Facility Name
Hillerød Hospital
City
Hillerød
Country
Denmark
Facility Name
Hjørring Hospital
City
Hjørring
Country
Denmark
Facility Name
Holbæk Hospital
City
Holbæk
Country
Denmark
Facility Name
Holstebro Hospital
City
Holstebro
Country
Denmark
Facility Name
Køge Hospital
City
Køge
Country
Denmark
Facility Name
Næstved Hospital
City
Næstved
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Facility Name
Slagelse Hospital
City
Slagelse
Country
Denmark
Facility Name
Sønderborg Hospital
City
Sønderborg
Country
Denmark
Facility Name
Vejle Hospital
City
Vejle
Country
Denmark
Facility Name
Dept of Intensive Care, Helsinki University Hospital
City
Helsinki
Country
Finland
Facility Name
Dept. of Intensive Care, Kuopio University Hospital
City
Kuopio
Country
Finland
Facility Name
Dept of Intensive Care, Tampere University Hospital
City
Tampere
Country
Finland
Facility Name
Dept. of Intensive Care, Landspitali
City
Reykjavik
Country
Iceland
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Facility Name
Stavanger University Hospital
City
Stavanger
Country
Norway
Facility Name
Intensive Care Unit, University Hospital of North Norway
City
Tromsø
Country
Norway
Facility Name
St Olavs Hospital, Trondheim University Hospital
City
Trondheim
Country
Norway

12. IPD Sharing Statement

Citations:
PubMed Identifier
21269526
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.
Results Reference
background
PubMed Identifier
22738085
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. Erratum In: N Engl J Med. 2012 Aug 2;367(5):481.
Results Reference
result
PubMed Identifier
25907781
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.
Results Reference
derived
PubMed Identifier
24807084
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.
Results Reference
derived
PubMed Identifier
24037226
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.
Results Reference
derived

Learn more about this trial

Scandinavian Starch for Severe Sepsis/Septic Shock Trial

We'll reach out to this number within 24 hrs