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.
BACKGROUND
By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis.


METHODS
The 6S trial will randomize 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%.


CONCLUSIONS
The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed.


BACKGROUND
ClinicalTrials.gov: NCT00962156.
Department of Intensive Care, Centre of Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Denmark. anders.perner@rh.regionh.dk
Anders
A
Perner
Nicolai
N
Haase
Jørn
J
Wetterslev
Anders
A
Aneman
Jyrki
J
Tenhunen
Anne Berit
AB
Guttormsen
Gudmundur
G
Klemenzson
Frank
F
Pott
Karen Doris
KD
Bødker
Per Martin
PM
Bådstøløkken
Asger
A
Bendtsen
Peter
P
Søe-Jensen
Hamid
H
Tousi
Morten
M
Bestle
Malgorzata
M
Pawlowicz
Robert
R
Winding
Hans-Henrik
HH
Bülow
Claude
C
Kancir
Morten
M
Steensen
Jonas
J
Nielsen
Bjarne
B
Fogh
Kristian R
KR
Madsen
Nils H
NH
Larsen
Marcela
M
Carlsson
Jørgen
J
Wiis
John Asger
JA
Petersen
Susanne
S
Iversen
Ole
O
Schøidt
Siv
S
Leivdal
Pawel
P
Berezowicz
Ville
V
Pettilä
Esko
E
Ruokonen
Pål
P
Klepstad
Sari
S
Karlsson
Maija
M
Kaukonen
Juha
J
Rutanen
Sigurbergur
S
Karason
Anne Lene
AL
Kjældgaard
Lars Broksø
LB
Holst
Jan
J
Wernerman
D000328:Adult; D000077324:Crystalloid Solutions; D004311:Double-Blind Method; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry / Q000627:therapeutic use*; D007552:Isotonic Solutions / Q000737:chemistry / Q000627:therapeutic use; D008970:Molecular Weight; D010952:Plasma Substitutes / Q000737:chemistry / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000401:mortality*; D012107:Research Design; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality*; D012720:Severity of Illness Index
D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes
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