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

This study has been completed.
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
University of Copenhagen
B. Braun Melsungen AG
Information provided by (Responsible Party):
Anders Perner, Scandinavian Critical Care Trials Group
ClinicalTrials.gov Identifier:
NCT00962156
First received: August 18, 2009
Last updated: July 9, 2012
Last verified: July 2012
  Purpose
  • 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.

Condition Intervention Phase
Severe Sepsis
Septic Shock
Drug: 6% Hydroxyethyl starch 130/0.4
Drug: Ringers acetate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Hydroxyethyl Starch 130/0.4 Compared With Balanced Crystalloid Solution on Mortality and Kidney Failure in Patients With Severe Sepsis

Resource links provided by NLM:


Further study details as provided by Scandinavian Critical Care Trials Group:

Primary Outcome Measures:
  • Mortality or dialysis-dependency [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Severity organ failure assessment score [ Time Frame: Day 5 ] [ Designated as safety issue: Yes ]
    Excluding Glascow coma score

  • Days free of ventilation [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Among survivors

  • Days free of dialysis [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Among survivors

  • Serious adverse reactions [ Time Frame: Followed up until ICU discharge; consequently the time frame will vary among patients ] [ Designated as safety issue: Yes ]
    Severe bleeding or severe allergic reactions

  • Need of dialysis/haemofiltration [ Time Frame: Within 90 days ] [ Designated as safety issue: No ]
  • Need of ventilation [ Time Frame: Within 90 days ] [ Designated as safety issue: No ]
  • Kidney failure [ Time Frame: Followed up until ICU discharge; consequently the time frame will vary among patients ] [ Designated as safety issue: No ]
    Severity organ failure assessment score > 2 in the renal component

  • Hospital length of stay [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Coagulation analyses [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    At selected hospitals whole-blood and biochemical coagulation analyses constitute additional secondary endpoints

  • NGAL [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    At selected trial sites will plasma and urinary NGAL be analysed at randomisation to assess the predictive value for dialyse and kidney failure


Enrollment: 804
Study Start Date: December 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HES 130/0.4
Volume expansion
Drug: 6% Hydroxyethyl starch 130/0.4
Infusion for volume expansion in the ICU
Other Name: 6% Tetraspan
Active Comparator: Ringer acetate
Volume expansion
Drug: Ringers acetate
Infusion for volume expansion in the ICU
Other Name: Ringerfundin / Sterofundin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00962156

Locations
Denmark
Rigshospitalet
Copenhagen, Denmark
Glostrup Hospital
Copenhagen, Denmark
Gentofte Hosptial
Copenhagen, Denmark
Hvidovre Hospital
Copenhagen, Denmark
Herlev Hospital
Copenhagen, Denmark
Bispebjerg Hospital
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, Denmark
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, Finland
Iceland
Dept. of Intensive Care, Landspitali
Reykjavik, Iceland
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, Norway
Sponsors and Collaborators
Anders Perner
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
University of Copenhagen
B. Braun Melsungen AG
Investigators
Principal Investigator: Anders Perner, MD, PhD ICU, Rigshospitalet, University of Copenhagen
Study Director: Nicolai Haase, MD Rigshospitalet, Denmark
  More Information

Additional Information:
Publications:
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(1):24. doi: 10.1186/1745-6215-12-24.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anders Perner, Chairman, Scandinavian Critical Care Trials Group
ClinicalTrials.gov Identifier: NCT00962156     History of Changes
Other Study ID Numbers: 2008-262, EudraCT no. 2009-010104-28
Study First Received: August 18, 2009
Last Updated: July 9, 2012
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Scandinavian Critical Care Trials Group:
Sepsis
Shock
Fluid therapy
Plasma expanders

Additional relevant MeSH terms:
Sepsis
Toxemia
Shock
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Hydroxyethyl Starch Derivatives
Plasma Substitutes
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014