Crystalloid Versus Hydroxyethyl Starch Trials

Study Overview
=================
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.

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

Conditions
-----------------
Intensive Care

Intervention / Treatment
-----------------
* Drug: 6% Hydroxy-ethyl starch (130/0.4)
* Drug: Saline


Participation Criteria
=================
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: 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 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxy-ethyl starch<br>Intravenous fluid resuscitation with 6% Hydroxy-ethyl starch (130/0.4) | Drug: 6% Hydroxy-ethyl starch (130/0.4)<br>* Maximum dose of 50ml/kg/day of 6% hydroxy-ethyl starch (130/0.4) for intravascular volume fluid resuscitation<br>* Other names: Voluven 6%;|
| Active Comparator: Saline<br>Intravenous fluid resuscitation with saline (0.9% sodium chloride) | Drug: Saline<br>* Maximum dose of 50ml/kg/day of saline for intravascular volume fluid resuscitation<br>* Other names: Sodium Chloride 0.9%;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intensive Care, Fluid Resuscitation, Saline, Hydroxy-ethyl starch