Crystalloid Versus Hydroxyethyl Starch Trials

NCT ID: NCT00935168

Last Updated: 2012-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 7000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-09-30

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.

Detailed Description

Patients in intensive care units frequently require intravenous fluid because the treating clinicians consider that the patient's blood pressure or circulating blood volume needs to be increased to clinically acceptable levels. Despite fluid resuscitation being a fundamental part of standard medical treatment for critically ill patients, clinicians are left with uncertainty about the optimal choice and volume of fluid that should be administered.

This study is a prospective, multi-centre, blinded, randomised controlled trial.

The two fluids being compared are 0.9% sodium chloride (saline) and 6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride,(starch). The null hypothesis assumes no difference in all-cause mortality between patients given starch in comparison with patients given saline for fluid resuscitation.

Each patient who meets all inclusion criteria and none of the exclusion criteria will be randomised to receive one of the two study fluids for fluid resuscitation.

Once treatment has been assigned the participant will continue to receive either starch or saline only for all fluid resuscitation requirements in intensive care. The treating clinical team will decide the amount and frequency of the fluid given for resuscitation based on standard care.

During their ICU stay, participants will have information on the use of study fluids, other fluids, kidney function, blood pressure, heart rate and other haemodynamic data that is routinely recorded in the medical record collected. All participants will be followed up at day 90 and at 6 months after randomisation.

The participants status (alive, in hospital and length of stay) will be recorded at day 28 and day 90 after randomisation. At the 6 month follow-up all participants or their carer will be interviewed by telephone using standardised questionnaires about the participant's quality of life. In addition, participants who were admitted to intensive care with a traumatic brain injury will be interviewed to determine how well the participant is recovering.

After all patients have completed the 6 months of follow-up, data linkage will also be used to link patients (in NSW only) to health databases in order to obtain information on their use of health services.

Conditions

Intensive Care

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hydroxy-ethyl starch

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

Group Type: EXPERIMENTAL

6% Hydroxy-ethyl starch (130/0.4)

Intervention Type: DRUG

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

Saline

Intravenous fluid resuscitation with saline (0.9% sodium chloride)

Group Type: ACTIVE_COMPARATOR

Saline

Intervention Type: DRUG

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

Interventions

6% Hydroxy-ethyl starch (130/0.4)

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

Intervention Type: DRUG

Saline

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

Intervention Type: DRUG

Other Intervention Names

Voluven 6%; Sodium Chloride 0.9%

Eligibility Criteria

Inclusion Criteria

• 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:

1. Heart rate > 90 beats per minute

2. Systolic blood pressure (SBP) < 100mmHg or mean arterial pressure (MAP) < 75mmHg or at least 40mmHg decrease in SBP or MAP from the baseline recording

3. Central venous pressure < 10mmHg

4. Pulmonary artery wedge pressure < 12 mmHg

5. Respiratory variation in systolic or mean arterial blood pressure of >5 mmHg

6. Capillary refill time > one second

7. Urine output < 0.5 ml/kg for one hour

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sydney

OTHER

Sponsor Role: collaborator

Australian and New Zealand Intensive Care Society Clinical Trials Group

NETWORK

Sponsor Role: collaborator

Fresenius Kabi

INDUSTRY

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John A Myburgh, PhD FJFICM

Role: STUDY_CHAIR

The George Institute

Simon Finfer

Role: PRINCIPAL_INVESTIGATOR

Royal North Shore Hospital, NSW, Australia

David Gattas

Role: PRINCIPAL_INVESTIGATOR

Royal Prince Alfred Hospital, NSW, Australia

Eddie Stachowski

Role: PRINCIPAL_INVESTIGATOR

Westmead Hospital, NSW, Australia

Michael Parr

Role: PRINCIPAL_INVESTIGATOR

Liverpool Hospital, NSW, Australia

Ian Seppelt

Role: PRINCIPAL_INVESTIGATOR

Nepean Hospital, NSW, Australia

Peter Harrigan

Role: PRINCIPAL_INVESTIGATOR

John Hunter Hospital, NSW, Australia

Rinaldo Bellomo

Role: PRINCIPAL_INVESTIGATOR

Austin Hospital, VIC, Australia

Forbes McGain

Role: PRINCIPAL_INVESTIGATOR

Western Hospital, VIC, Australia

Rob Boots

Role: PRINCIPAL_INVESTIGATOR

Royal Brisbane & Women's Hospital, QLD, Australia

Jason Fletcher

Role: PRINCIPAL_INVESTIGATOR

Bendigo Health, VIC, Australia

David Milliss

Role: PRINCIPAL_INVESTIGATOR

Concord Hospital, NSW, Australia

Benno Ihle

Role: PRINCIPAL_INVESTIGATOR

Epworth Richmond, VIC, Australia

David Ernest

Role: PRINCIPAL_INVESTIGATOR

Box Hill Hospital, VIC, Australia

Jeffrey Presneill

Role: PRINCIPAL_INVESTIGATOR

Mater Health Services, QLD, Australia

Claire Cattigan

Role: PRINCIPAL_INVESTIGATOR

Geelong Hospital, VIC, Australia

Katrina Ellem

Role: PRINCIPAL_INVESTIGATOR

Calvary Mater Newcastle, NSW, Australia

Seton Henderson

Role: PRINCIPAL_INVESTIGATOR

Christchurch Hospital, New Zealand

Shay McGuinness

Role: PRINCIPAL_INVESTIGATOR

Auckland CVICU, New Zealand

Dick Dinsdale

Role: PRINCIPAL_INVESTIGATOR

Wellington Hospital, New Zealand

Michael Reade

Role: PRINCIPAL_INVESTIGATOR

The Northen Hospital, VIC, Australia

Bart de Keulenaer

Role: PRINCIPAL_INVESTIGATOR

Fremantle Hospital, WA, Australia

Latesh Poojara

Role: PRINCIPAL_INVESTIGATOR

Blacktown Hospital, NSW, Australia

Yahya Shehabi

Role: PRINCIPAL_INVESTIGATOR

Prince of Wales Hospital, NSW, Australia

Imogen Mitchell

Role: PRINCIPAL_INVESTIGATOR

The Canberra Hospital, ACT, Australia

John Santamaria

Role: PRINCIPAL_INVESTIGATOR

St Vincent's Hospital, VIC, Australia

Troy Browne

Role: PRINCIPAL_INVESTIGATOR

Tauranga Hospital, New Zealand

Kavi Haji

Role: PRINCIPAL_INVESTIGATOR

Frankston Hospital, VIC Australia

Frank van Haren

Role: PRINCIPAL_INVESTIGATOR

Waikato Hospital, New Zealand

Janet Liang

Role: PRINCIPAL_INVESTIGATOR

North Shore Hospital, New Zealand

Bala Venkatesh

Role: PRINCIPAL_INVESTIGATOR

Wesley Hospital, VIC, Australia

David Cooper

Role: PRINCIPAL_INVESTIGATOR

Royal Hobart Hospital, TAS, Australia

John Myburgh

Role: PRINCIPAL_INVESTIGATOR

St George Hospital, NSW, Australia

Locations

The George Institute for International Health

Sydney, New South Wales, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 27324967 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23731998 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23075127 (View on PubMed)

Other Identifiers

ACTRN12609000245291

Identifier Type: REGISTRY

Identifier Source: secondary_id

GI-CCT24378

Identifier Type: -

Identifier Source: org_study_id