Crystalloid Versus Hydroxyethyl Starch Trials - Full Text View

Sponsor:	The George Institute
Collaborators:	University of Sydney Australian and New Zealand Intensive Care Society Clinical Trials Group Fresenius Kabi
Information provided by (Responsible Party):	The George Institute
ClinicalTrials.gov Identifier:	NCT00935168

Purpose

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.

Condition	Intervention	Phase
Intensive Care	Drug: 6% Hydroxy-ethyl starch (130/0.4) Drug: Saline	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Chlorides Sodium chloride Starch Hetastarch

U.S. FDA Resources

Further study details as provided by The George Institute:

Primary Outcome Measures:

All cause mortality [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
ICU, hospital and 28 day mortality [ Time Frame: At 28 days and 6 months after randomisation ] [ Designated as safety issue: Yes ]
Quality of life will be assessed using the EQ-5D questionnaire. [ Time Frame: 6 months after randomisation ] [ Designated as safety issue: No ]
Functional status will be assessed using the Glasgow Outcome score. [ Time Frame: 6 months after randomisation. ] [ Designated as safety issue: No ]

Estimated Enrollment:	7000
Study Start Date:	December 2009
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Hydroxy-ethyl starch Intravenous fluid resuscitation with 6% Hydroxy-ethyl starch (130/0.4)	Drug: 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 Other Name: Voluven 6%
Active Comparator: Saline Intravenous fluid resuscitation with saline (0.9% sodium chloride)	Drug: Saline Maximum dose of 50ml/kg/day of saline for intravascular volume fluid resuscitation Other Name: Sodium Chloride 0.9%

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00935168

Locations

Australia, New South Wales
The George Institute for International Health
Sydney, New South Wales, Australia, 2000

Sponsors and Collaborators

The George Institute

University of Sydney

Australian and New Zealand Intensive Care Society Clinical Trials Group

Fresenius Kabi

Investigators

Study Chair:	John A Myburgh, PhD FJFICM	The George Institute
Principal Investigator:	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

More Information

No publications provided

Responsible Party:	The George Institute
ClinicalTrials.gov Identifier:	NCT00935168 History of Changes
Other Study ID Numbers:	GI-CCT24378, ACTRN12609000245291
Study First Received:	July 1, 2009
Last Updated:	February 8, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration; New Zealand: Medsafe; New Zealand: Ministry of Health

Keywords provided by The George Institute:

Intensive Care
Fluid Resuscitation
Saline
Hydroxy-ethyl starch

Additional relevant MeSH terms:

Hetastarch
Plasma Substitutes
Blood Substitutes

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012