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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01424150
Registration number
NCT01424150
Ethics application status
Date submitted
25/08/2011
Date registered
26/08/2011
Date last updated
13/02/2018
Titles & IDs
Public title
REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery: RELIEF Study
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Scientific title
Restrictive Versus Liberal Fluid Therapy in Major Abdominal Surgery
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Secondary ID [1]
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164/11 Pilot - 544/12 Main
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Universal Trial Number (UTN)
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Trial acronym
RELIEF
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Abdominal Surgery
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Liberal fluid therapy
Other interventions - Restrictive fluid therapy
Experimental: Liberal - At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data.
Experimental: Restrictive - Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to =5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device [see below]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia.
Other interventions: Liberal fluid therapy
Liberal protocol group is designed to provide approximately 6.0L per day.
Other interventions: Restrictive fluid therapy
Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Disability-free survival
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Assessment method [1]
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Disability-free survival up to 1 year: survival and freedom from disability. The latter is defined as a persistent (=6 months) reduction in health status as measured by a 12-item version of WHODAS score of at least 24 points, reflecting a disability level of at least 25% and being the threshold point between "disabled" and "not disabled" as per WHO guidelines. Disability will be assessed by the participant, but if unable then we will use the proxy's report. The date of onset of new disability will be recorded. Further details are provided in the Procedures Manual and the Statistical Analysis Plan.
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Timepoint [1]
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1 year postoperative
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Secondary outcome [1]
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Death
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Assessment method [1]
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Timepoint [1]
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90 days, then up to 12 months after surgery
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Secondary outcome [2]
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A composite (pooled) and individual septic complications: sepsis, surgical site infection, anastomotic leak, and pneumonia
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Assessment method [2]
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As per individual definitions
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Timepoint [2]
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30 days postoperative
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Secondary outcome [3]
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Sepsis
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Assessment method [3]
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using Centers for Disease Control and Prevention (CDC) with National Healthcare Safety Network (NHSN) criteria, two or more features of the systematic inflammatory response syndrome (SIRS) plus evidence of a source or site of infection (can be positive blood culture or purulence from any site)
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Timepoint [3]
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30 days postoperative
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Secondary outcome [4]
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Surgical site infection
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Assessment method [4]
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using CDC criteria (http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf):
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Timepoint [4]
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30 days postoperative
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Secondary outcome [5]
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Pneumonia
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Assessment method [5]
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The presence of new and/or progressive pulmonary infiltrates on chest radiograph plus two or more of the following:
Fever = 38.5°C or postoperative hypothermia <36°C
Leukocytosis = 12,000 WBC/mm3 or leukopenia < 4,000 WBC/mm3
Purulent sputum and/or
New onset or worsening cough or dyspnoea.
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Timepoint [5]
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30 Days postoperative
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Secondary outcome [6]
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Acute kidney injury
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Assessment method [6]
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according to The Kidney Disease: Improving Global Outcomes (KDIGO) group criteria, but not urine output - for Stage 2 or worse AKI defined as at least 2-fold increase in creatinine, or estimated GFR decrease >50%.(73) We also plan to report renal replacement therapy up to 90 days after surgery. Because a restrictive IV fluid regimen may artificially elevate serum creatinine due to a smaller dilutional effect from less IV fluids, we therefore calculated adjusted creatinine by first estimating the volume of distribution for creatinine as equal to total body water (assumed to be 60% of body weight, expressed in mL).
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Timepoint [6]
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30 days postoperative
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Secondary outcome [7]
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Pulmonary oedema
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Assessment method [7]
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respiratory distress or impaired oxygenation AND radiological evidence of pulmonary oedema
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Timepoint [7]
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30 days postoperative
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Secondary outcome [8]
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Total ICU stay and mechanical ventilation time
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Assessment method [8]
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including initial ICU admission and readmission times
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Timepoint [8]
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30 day postoperative
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Secondary outcome [9]
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Hospital stay
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Assessment method [9]
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from the start (date, time) of surgery until actual hospital discharge
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Timepoint [9]
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30 days postoperative
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Secondary outcome [10]
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Quality of recovery
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Assessment method [10]
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15-item Quality of recovery score (QoR-15)
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Timepoint [10]
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days 1, 3 and day 30 postoperative
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Secondary outcome [11]
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Anastomotic leak
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Assessment method [11]
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A defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- an extra luminal compartments.
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Timepoint [11]
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30 days postoperative
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Secondary outcome [12]
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Inflammation
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Assessment method [12]
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plasma C-reactive protein (CRP, using site-specific assay) concentration on Day 3
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Timepoint [12]
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Day 3 postoperative
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Secondary outcome [13]
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Tissue perfusion
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Assessment method [13]
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peak serum lactate within 24 hours of surgery
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Timepoint [13]
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24 hours post surgery
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Secondary outcome [14]
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Any blood transfusion
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Assessment method [14]
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including red cell, fresh frozen plasma or platelet transfusion, from the commencement of surgery
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Timepoint [14]
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From surgery to Day 3 postoperative
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Secondary outcome [15]
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Total ICU stay and unplanned ICU admission to ICU
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Assessment method [15]
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additive, including initial ICU admission and readmission times up to Day 30
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Timepoint [15]
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30 days postoperative
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Eligibility
Key inclusion criteria
Inclusion criteria:
1. Adults (=18 years) undergoing elective major surgery and providing informed consent
2. All types of open or lap-assisted abdominal or pelvic surgery with an expected
duration of at least 2 hours, and an expected hospital stay of at least 3 days (for
example, oesophagectomy, gastrectomy, pancreatectomy, colectomy, aortic or
aorto-femoral vascular surgery, nephrectomy, cystectomy, open prostatectomy, radical
hysterectomy, and abdominal incisional hernia repair)
3. At increased risk of postoperative complications, defined as at least one of the
following criteria:
- age =70 years
- known or documented history of coronary artery disease
- known or documented history of heart failure
- diabetes currently treated with an oral hypoglycaemic agent and/or insulin
- preoperative serum creatinine >200 µmol/L (>2.8 mg/dl)
- morbid obesity (BMI =35 kg/m²)
- preoperative serum albumin <30 g/L
- anaerobic threshold (if done) <12 mL/kg/min
- or two or more of the following risk factors:
- ASA 3 or 4
- chronic respiratory disease
- obesity (BMI 30-35 kg/m²)
- aortic or peripheral vascular disease
- preoperative haemoglobin <100 g/L
- preoperative serum creatinine 150-199 µmol/L (>1.7 mg/dl)
- anaerobic threshold (if done) 12-14 mL/kg/min
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion Criteria
1. Urgent or time-critical surgery
2. ASA physical status 5 - such patients are not expected to survive with or without
surgery, and their underlying illness is expected to have an overwhelming effect on
outcome (irrespective of fluid therapy)
3. Chronic renal failure requiring dialysis
4. Pulmonary or cardiac surgery - different pathophysiology, and thoracic surgery
typically have strict fluid restrictions
5. Liver resection - most units have strict fluid/CVP limits in place and won't allow
randomisation
6. Minor or intermediate surgery, such as laparoscopic cholecystectomy, transurethral
resection of the prostate, inguinal hernia repair, splenectomy, closure of colostomy -
each of these are typically "minor" surgery with minimal IV fluid requirements,
generally low rates of complications and mostly very good survival.
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Study design
Purpose of the study
Supportive Care
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people assessing the outcomes
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/07/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
22/10/2017
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Sample size
Target
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Accrual to date
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Final
3000
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Alfred Hospital - Melbourne
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Recruitment postcode(s) [1]
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3004 - Melbourne
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Funding & Sponsors
Primary sponsor type
Other
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Name
Bayside Health
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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National Health and Medical Research Council, Australia
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
The optimal fluid regimen, haemodynamic (or other) targets and fluid choice (colloid or
crystalloid) for patients undergoing major surgery are based on rationales that are not
supported by strong evidence. Practices vary substantially, guidelines are vague, small
trials and meta-analyses are contradictory. The strongest and most consistent evidence, and
biological plausibility because of tissue edema, supports a restrictive fluid strategy. But
other evidence supports goal-directed therapy, requiring additional IV fluid. There is no
good evidence that use and choice of colloids improves outcome. RELIEF will study the effects
of fluid restriction, and the possible effect-modification of goal-directed therapy and
colloids. The first will be randomly assigned; the latter will be measured covariates
dictated by local practices and beliefs.
Study Hypotheses A restrictive fluid regimen for adults undergoing major abdominal surgery
leads to reduced complications and improved disability-free survival when compared with a
liberal fluid regimen.
Secondary hypothesis: The effects of fluid restriction are similar whether or not
goal-directed therapy is used (assessed as a statistical test of interaction). A restrictive
fluid regimen will reduce a composite of 30-day septic complications and mortality.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01424150
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Paul S Myles, MB.BS, MPH, MD, FANZCA
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Address
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Alfred Hospital, Monash University
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01424150
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