Intensive CarePhase 3CHESTNCT00935168
Crystalloid Versus Hydroxyethyl Starch Trials
A Phase 3 study testing 6% Hydroxy-ethyl starch (130/0.4) and Saline in people with Intensive Care, run by The George Institute at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intensive Care
- What is being tested?
- 6% Hydroxy-ethyl starch (130/0.4) and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7,000 participants
- Where
- 1 siteAustralia
- Study dates
- Dec 2009to Sep 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Australia1 site
The George Institute for International Health
Sydney, New South Wales, 2000
About this study
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
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.
Read the 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
- Being tested
- 6% Hydroxy-ethyl starch (130/0.4), Saline
- Keywords
- Intensive Care, Fluid Resuscitation, Saline, Hydroxy-ethyl starch
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6% Hydroxy-ethyl starch (130/0.4)Drug
Also called Voluven 6%
Maximum dose of 50ml/kg/day of 6% hydroxy-ethyl starch (130/0.4) for intravascular volume fluid resuscitation
SalineDrug
Also called Sodium Chloride 0.9%
Maximum dose of 50ml/kg/day of saline for intravascular volume fluid resuscitation
| Study group | Role | What they receive |
|---|---|---|
| Hydroxy-ethyl starch | Experimental | Intravenous fluid resuscitation with 6% Hydroxy-ethyl starch (130/0.4) Receives: Drug: 6% Hydroxy-ethyl starch (130/0.4) |
| Saline | Active comparator | Intravenous fluid resuscitation with saline (0.9% sodium chloride) Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
All cause mortality
Measured: 90 days
Secondary outcomes (5)
Renal failure requiring renal replacement therapy will be assessed using hospital records.
Measured: 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.
Measured: During ICU stay after randomisation up to 90 days
ICU, hospital and 28 day mortality
Measured: At 28 days and 6 months after randomisation
Quality of life will be assessed using the EQ-5D questionnaire.
Measured: 6 months after randomisation
Functional status will be assessed using the Glasgow Outcome score.
Measured: 6 months after randomisation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2009 (estimated)
- Study startDec 2009
- Primary completionApr 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Intensive CareStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sydney, Australian and New Zealand Intensive Care Society Clinical Trials Group, Fresenius Kabi
- Responsible party
- Sponsor
- Investigators
- John A Myburgh, PhD FJFICM, Study chair, The George InstituteSimon Finfer, Principal investigator, Royal North Shore Hospital, NSW, AustraliaDavid Gattas, Principal investigator, Royal Prince Alfred Hospital, NSW, AustraliaEddie Stachowski, Principal investigator, Westmead Hospital, NSW, AustraliaMichael Parr, Principal investigator, Liverpool Hospital, NSW, AustraliaIan Seppelt, Principal investigator, Nepean Hospital, NSW, AustraliaPeter Harrigan, Principal investigator, John Hunter Hospital, NSW, AustraliaRinaldo Bellomo, Principal investigator, Austin Hospital, VIC, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00935168
- Sponsor's protocol ID
- GI-CCT24378
- Other IDs
- ACTRN12609000245291
- Acronym
- CHEST
- Status last verified
- Feb 2012
- First submitted
- 1 Jul 2009
- Last updated
- 16 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27324967Phillips 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.
PubMed 23731998Myburgh 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.
PubMed 23075127
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00935168
- Acronym / sponsor ID
- CHEST / GI-CCT24378
- Conditions
- Intensive Care
- Keywords
- Intensive Care, Fluid Resuscitation, Saline, Hydroxy-ethyl starch
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7,000 participants (actual)
- Lead sponsor
- The George InstituteUniversity, hospital or other
- Collaborators
- University of Sydney, Australian and New Zealand Intensive Care Society Clinical Trials Group, Fresenius Kabi
- Study start
- Dec 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 8 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxy-ethyl starch | Experimental | Drug: 6% Hydroxy-ethyl starch (130/0.4)Intravenous fluid resuscitation with 6% Hydroxy-ethyl starch (130/0.4) |
| Saline | Active comparator | Drug: SalineIntravenous fluid resuscitation with saline (0.9% sodium chloride) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6% Hydroxy-ethyl starch (130/0.4)Also: Voluven 6%Maximum dose of 50ml/kg/day of 6% hydroxy-ethyl starch (130/0.4) for intravascular volume fluid resuscitation | Drug | Hydroxy-ethyl starch |
| SalineAlso: Sodium Chloride 0.9%Maximum dose of 50ml/kg/day of saline for intravascular volume fluid resuscitation | Drug | Saline |
Primary outcome
All cause mortality
Time frame: 90 days
5 secondary outcomes
Renal failure requiring renal replacement therapy will be assessed using hospital records.
Time frame: 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.
Time frame: During ICU stay after randomisation up to 90 days
ICU, hospital and 28 day mortality
Time frame: At 28 days and 6 months after randomisation
Quality of life will be assessed using the EQ-5D questionnaire.
Time frame: 6 months after randomisation
Functional status will be assessed using the Glasgow Outcome score.
Time frame: 6 months after randomisation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2012.
- Derived from this study: PubMed 27324967Taylor 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.
- Derived from this study: PubMed 23731998Phillips 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.
- Derived from this study: PubMed 23075127Myburgh 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John A Myburgh, PhD FJFICM study chair
The George Institute
Simon Finfer principal investigator
Royal North Shore Hospital, NSW, Australia
David Gattas principal investigator
Royal Prince Alfred Hospital, NSW, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 6% Hydroxy-ethyl starch (130/0.4) and Saline in people with Intensive Care, run by The George Institute at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All cause mortality (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00935168, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2012.