Clinical trial NCT00935168: Crystalloid Versus Hydroxyethyl Starch Trials
Official title: A Multi-centre Randomized Controlled Trial of Fluid Resuscitation With Starch (6%Hydroxyethyl Starch 130/0.4) Compared to Saline (0.9% Sodium Chloride) in Intensive Care Patients on Mortality
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intensive Care
Keywords: Intensive Care
Fluid Resuscitation
Saline
Hydroxy-ethyl starch
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: University of Sydney
name: Australian and New Zealand Intensive Care Society Clinical Trials Group
name: Fresenius Kabi
First posted: 2009-07-08
Enrollment: 7000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: All cause mortality
timeFrame: 90 days
Secondary outcomes:
measure: Renal failure requiring renal replacement therapy will be assessed using hospital records.
timeFrame: During intensive care Unit (ICU) stay after randomisation up to 90 days
measure: 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.
timeFrame: During ICU stay after randomisation up to 90 days
measure: ICU, hospital and 28 day mortality
timeFrame: At 28 days and 6 months after randomisation
measure: Quality of life will be assessed using the EQ-5D questionnaire.
timeFrame: 6 months after randomisation
measure: Functional status will be assessed using the Glasgow Outcome score.
timeFrame: 6 months after randomisation.
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: The George Institute for International Health
state: New South Wales
Study officials:
affiliation: The George Institute
name: John A Myburgh, PhD FJFICM
role: STUDY_CHAIR
affiliation: Royal North Shore Hospital, NSW, Australia
name: Simon Finfer
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Prince Alfred Hospital, NSW, Australia
name: David Gattas
role: PRINCIPAL_INVESTIGATOR
affiliation: Westmead Hospital, NSW, Australia
name: Eddie Stachowski
role: PRINCIPAL_INVESTIGATOR
affiliation: Liverpool Hospital, NSW, Australia
name: Michael Parr
role: PRINCIPAL_INVESTIGATOR
affiliation: Nepean Hospital, NSW, Australia
name: Ian Seppelt
role: PRINCIPAL_INVESTIGATOR
affiliation: John Hunter Hospital, NSW, Australia
name: Peter Harrigan
role: PRINCIPAL_INVESTIGATOR
affiliation: Austin Hospital, VIC, Australia
name: Rinaldo Bellomo
role: PRINCIPAL_INVESTIGATOR
affiliation: Western Hospital, VIC, Australia
name: Forbes McGain
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Brisbane & Women's Hospital, QLD, Australia
name: Rob Boots
role: PRINCIPAL_INVESTIGATOR
affiliation: Bendigo Health, VIC, Australia
name: Jason Fletcher
role: PRINCIPAL_INVESTIGATOR
affiliation: Concord Hospital, NSW, Australia
name: David Milliss
role: PRINCIPAL_INVESTIGATOR
affiliation: Epworth Richmond, VIC, Australia
name: Benno Ihle
role: PRINCIPAL_INVESTIGATOR
affiliation: Box Hill Hospital, VIC, Australia
name: David Ernest
role: PRINCIPAL_INVESTIGATOR
affiliation: Mater Health Services, QLD, Australia
name: Jeffrey Presneill
role: PRINCIPAL_INVESTIGATOR
affiliation: Geelong Hospital, VIC, Australia
name: Claire Cattigan
role: PRINCIPAL_INVESTIGATOR
affiliation: Calvary Mater Newcastle, NSW, Australia
name: Katrina Ellem
role: PRINCIPAL_INVESTIGATOR
affiliation: Christchurch Hospital, New Zealand
name: Seton Henderson
role: PRINCIPAL_INVESTIGATOR
affiliation: Auckland CVICU, New Zealand
name: Shay McGuinness
role: PRINCIPAL_INVESTIGATOR
affiliation: Wellington Hospital, New Zealand
name: Dick Dinsdale
role: PRINCIPAL_INVESTIGATOR
affiliation: The Northen Hospital, VIC, Australia
name: Michael Reade
role: PRINCIPAL_INVESTIGATOR
affiliation: Fremantle Hospital, WA, Australia
name: Bart de Keulenaer
role: PRINCIPAL_INVESTIGATOR
affiliation: Blacktown Hospital, NSW, Australia
name: Latesh Poojara
role: PRINCIPAL_INVESTIGATOR
affiliation: Prince of Wales Hospital, NSW, Australia
name: Yahya Shehabi
role: PRINCIPAL_INVESTIGATOR
affiliation: The Canberra Hospital, ACT, Australia
name: Imogen Mitchell
role: PRINCIPAL_INVESTIGATOR
affiliation: St Vincent's Hospital, VIC, Australia
name: John Santamaria
role: PRINCIPAL_INVESTIGATOR
affiliation: Tauranga Hospital, New Zealand
name: Troy Browne
role: PRINCIPAL_INVESTIGATOR
affiliation: Frankston Hospital, VIC Australia
name: Kavi Haji
role: PRINCIPAL_INVESTIGATOR
affiliation: Waikato Hospital, New Zealand
name: Frank van Haren
role: PRINCIPAL_INVESTIGATOR
affiliation: North Shore Hospital, New Zealand
name: Janet Liang
role: PRINCIPAL_INVESTIGATOR
affiliation: Wesley Hospital, VIC, Australia
name: Bala Venkatesh
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Hobart Hospital, TAS, Australia
name: David Cooper
role: PRINCIPAL_INVESTIGATOR
affiliation: St George Hospital, NSW, Australia
name: John Myburgh
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.