Crystalloid Versus Hydroxyethyl Starch Trials

NCT00935168 | Completed Phase 3 DMC

• 2 other identifiers: GI-CCT24378ACTRN12609000245291
• Study Type: interventional
• Target: 7,000
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determine whether patients in the Intensive Care Unit who receive fluid resuscitation with either hydroxyethyl starch (a synthetic colloid solution) or saline (a salt solution), have an increased rate of survival at 90 days.

Conditions

Intensive Care

Keywords

Intensive Care; Fluid Resuscitation; Saline; Hydroxy-ethyl starch

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  90 days

Secondary Outcomes (5)

• Renal failure requiring renal replacement therapy will be assessed using hospital records.

  During intensive care Unit (ICU) stay after randomisation up to 90 days

• Other organ failures will be assessed using the Sequential Organ Failure Assessment (SOFA) score which is based on biochemical and bio-physiological parameters recorded in the hospital record.

  During ICU stay after randomisation up to 90 days

• ICU, hospital and 28 day mortality

  At 28 days and 6 months after randomisation

• Quality of life will be assessed using the EQ-5D questionnaire.

  6 months after randomisation

• Functional status will be assessed using the Glasgow Outcome score.

  6 months after randomisation.

Study Arms (2)

Hydroxy-ethyl starch

EXPERIMENTAL

Intravenous fluid resuscitation with 6% Hydroxy-ethyl starch (130/0.4)

Drug: 6% Hydroxy-ethyl starch (130/0.4)

Saline

ACTIVE COMPARATOR

Intravenous fluid resuscitation with saline (0.9% sodium chloride)

Drug: Saline

Interventions

6% Hydroxy-ethyl starch (130/0.4) DRUG

Maximum dose of 50ml/kg/day of 6% hydroxy-ethyl starch (130/0.4) for intravascular volume fluid resuscitation

Also known as: Voluven 6%

Hydroxy-ethyl starch

Saline DRUG

Maximum dose of 50ml/kg/day of saline for intravascular volume fluid resuscitation

Also known as: Sodium Chloride 0.9%

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent has been obtained or if not possible, the procedure for obtaining informed consent has been approved by the ethics committee.
• Fluid resuscitation is required to increase or maintain intravascular volume that is in addition to maintenance fluids, enteral and parenteral nutrition, blood products and specific replacement fluids to replace ongoing insensible or fluid losses from other sites (e.g., fistula losses from the gastrointestinal tract, urinary losses from diabetes insipidus or the polyuric phase of acute renal failure or to correct metabolic derangements).
• The ICU clinician considers that both 6% hydroxyethyl starch (130/0.4) and saline are equally appropriate for the patient and that no specific indication or contraindication for either exists.
• The requirement for fluid resuscitation must be supported by AT LEAST ONE of the following clinical signs:
• Heart rate \> 90 beats per minute
• Systolic blood pressure (SBP) \< 100mmHg or mean arterial pressure (MAP) \< 75mmHg or at least 40mmHg decrease in SBP or MAP from the baseline recording
• Central venous pressure \< 10mmHg
• Pulmonary artery wedge pressure \< 12 mmHg
• Respiratory variation in systolic or mean arterial blood pressure of \>5 mmHg
• Capillary refill time \> one second
• Urine output \< 0.5 ml/kg for one hour

You may not qualify if:

• Previous allergic reaction to hydroxyethyl starch solution.
• Primary non-traumatic intracranial haemorrhage or severe traumatic intracranial haemorrhage (mass lesion \> 25 ml).
• Patients who are receiving renal replacement therapy or in whom the ICU physician considers renal replacement therapy is imminent (i.e. renal replacement therapy will start in 6 hours)
• Patients with documented serum creatinine value ≥ 350µmol/L and urine output averaging ≤ 10ml / hr over 12 hours
• Severe hypernatraemia (Serum sodium \> 160 mmol/l) or severe hyperchloraemia (Serum chloride \> 130 mmol/l).
• Women of child bearing age (18-49 years old), unless evidence of documented menopause, hysterectomy or surgical sterilisation or negative pregnancy test before randomisation
• Breastfeeding
• Patients who have received \> 1000mL hydroxyethyl starch in the 24 hours before randomization.
• Patients admitted to the ICU following cardiac surgery; patients admitted to ICU following cardiac surgery.
• Patients admitted to the ICU for the treatment of burns or following liver transplantation surgery.
• Death is deemed imminent and inevitable or the patient has an underlying disease process with a life expectancy of \< 90 days.
• A limitation of therapy order has been documented restricting implementation of the study protocol or the treating clinician deems aggressive care unsuitable.
• Patient has previously been enrolled in the CHEST study.
• Patient has previously received fluid resuscitation that was prescribed within the study ICU during this current ICU admission.
• Patient has been transferred to the study ICU from another ICU and received fluid resuscitation for the treatment of volume depletion in that other ICU.

Sponsors & Collaborators

• The George Institute: lead
• University of Sydney: collaborator
• Australian and New Zealand Intensive Care Society Clinical Trials Group: collaborator
• Fresenius Kabi: collaborator

Study Sites (1)

The George Institute for International Health

Sydney, New South Wales, 2000, Australia

Location

Related Publications (3)

• Taylor C, Thompson K, Finfer S, Higgins A, Jan S, Li Q, Liu B, Myburgh J; Crystalloid versus Hydroxyethyl Starch Trial (CHEST) investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch versus saline for resuscitation of patients in intensive care: long-term outcomes and cost-effectiveness analysis of a cohort from CHEST. Lancet Respir Med. 2016 Oct;4(10):818-825. doi: 10.1016/S2213-2600(16)30120-5. Epub 2016 Jun 17.

  PMID: 27324967 DERIVED

• Phillips DP, Kaynar AM, Kellum JA, Gomez H. Crystalloids vs. colloids: KO at the twelfth round? Crit Care. 2013 May 29;17(3):319. doi: 10.1186/cc12708.

  PMID: 23731998 DERIVED

• Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012 Nov 15;367(20):1901-11. doi: 10.1056/NEJMoa1209759. Epub 2012 Oct 17.

  PMID: 23075127 DERIVED

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• John A Myburgh, PhD FJFICM

  The George Institute

  STUDY CHAIR

• Simon Finfer

  Royal North Shore Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• David Gattas

  Royal Prince Alfred Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Eddie Stachowski

  Westmead Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Michael Parr

  Liverpool Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Ian Seppelt

  Nepean Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Peter Harrigan

  John Hunter Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Rinaldo Bellomo

  Austin Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• Forbes McGain

  Western Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• Rob Boots

  Royal Brisbane & Women's Hospital, QLD, Australia

  PRINCIPAL INVESTIGATOR

• Jason Fletcher

  Bendigo Health, VIC, Australia

  PRINCIPAL INVESTIGATOR

• David Milliss

  Concord Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Benno Ihle

  Epworth Richmond, VIC, Australia

  PRINCIPAL INVESTIGATOR

• David Ernest

  Box Hill Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• Jeffrey Presneill

  Mater Health Services, QLD, Australia

  PRINCIPAL INVESTIGATOR

• Claire Cattigan

  Geelong Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• Katrina Ellem

  Calvary Mater Newcastle, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Seton Henderson

  Christchurch Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

• Shay McGuinness

  Auckland CVICU, New Zealand

  PRINCIPAL INVESTIGATOR

• Dick Dinsdale

  Wellington Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

• Michael Reade

  The Northen Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• Bart de Keulenaer

  Fremantle Hospital, WA, Australia

  PRINCIPAL INVESTIGATOR

• Latesh Poojara

  Blacktown Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Yahya Shehabi

  Prince of Wales Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

• Imogen Mitchell

  The Canberra Hospital, ACT, Australia

  PRINCIPAL INVESTIGATOR

• John Santamaria

  St Vincent's Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• Troy Browne

  Tauranga Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

• Kavi Haji

  Frankston Hospital, VIC Australia

  PRINCIPAL INVESTIGATOR

• Frank van Haren

  Waikato Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

• Janet Liang

  North Shore Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

• Bala Venkatesh

  Wesley Hospital, VIC, Australia

  PRINCIPAL INVESTIGATOR

• David Cooper

  Royal Hobart Hospital, TAS, Australia

  PRINCIPAL INVESTIGATOR

• John Myburgh

  St George Hospital, NSW, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 8, 2009
• Study Start: December 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 16, 2012

Record last verified: 2012-02

Locations

AU (1)