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Trial registered on ANZCTR


Registration number
ACTRN12612000023853
Ethics application status
Approved
Date submitted
30/12/2011
Date registered
6/01/2012
Date last updated
5/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Balanced fluid therapy and early kidney function in patients undergoing renal transplantation
Scientific title
A comparison of Plasmalyte Solution and 0.9% Sodium Chloride (NaCl) on acid base balance, hyperkalaemia and early kidney function in patients undergoing deceased donor (heart-beating or non heart-beating) renal transplantation: a randomised, blinded single centre pilot trial
Secondary ID [1] 279647 0
Nil
Universal Trial Number (UTN)
U1111-1126-7183
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal failure 285448 0
Renal transplantation 285449 0
Condition category
Condition code
Renal and Urogenital 285632 285632 0 0
Kidney disease
Anaesthesiology 285633 285633 0 0
Anaesthetics
Surgery 285634 285634 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Plasmalyte 148 Intravenous Fluid Solution

Plasma-lyte 148 (pH 7.4) is a replacement electrolyte intravenous infusion that provides electrolyte supplementation and water for hydration for patients undergoing major surgery including renal transplantation. In addition, the presence of bicarbonate precursors (acetate and gluconate) produces a metabolic alkalinising effect that helps counteract metabolic acidosis of patients with chronic kidney disease. It is an isontonic solution and compatible with blood or blood components. It may be added to or infused concurrently with blood components, or used as a diluent in the transfusion of packed erythrocytes.

The electrolyte composition of Plasmalyte is as follows:
Magnesium chloride .3 g/L
Potassium chloride .37 g/L
Sodium acetate 3.68 g/L
Sodium chloride 5.26 g/L
Sodium gluconate 5.02 g/L

For this clinical trial Plasmlayte solution will be used intraoperatively and postoperatively for 48 hours as the intravenous fluid solution for all patients undergoing cadaveric renal transplantation in our institution.

Doses:

The volume of Plasmlayte solution will be delivered based on routine clinical care under the guidance of the anaesthetists and renal physician. The fluid will be commenced immediately after the induction of anaesthesia and before the first surgical incision and discontinued after 48 post operative hours.

Intraoperatively: Plasmalyte will be given as per conventional anaesthesia practice with 10–30 mL/kg/hr to maintain mean arterial pressure (MAP) within 20% of baseline preoperative value.

Postoperative Management: Postoperatively as per renal unit protocols all patients will receive a maintenance infusion of Plasmalyte solution. The rate of the study fluid replacement is determined by the urine output as a “urine chaser”. Each hour the previous hour’s urine output + 30 ml will be replaced with trial fluid. The “urine chaser” is commenced in the recovery room and continues for the first 24 hours. The treating medical staff may alter the rate of fluid administration as clinically required. Any additional fluid boluses of trial drug crystalloid solution may be administered to any patient if volume supplementation is required. For the next 24-hours (day 2) any further crystalloid infusion consists of the study fluid, with the rate of the crystalloid infusion being at the discretion of the treating medical staff. After 48 hours the study fluid is no longer used and the rate and type of any further crystalloid administration is at the discretion of the treating medical staff.
Intervention code [1] 283931 0
Prevention
Intervention code [2] 283932 0
Treatment: Drugs
Intervention code [3] 283960 0
Other interventions
Comparator / control treatment
Normal Saline 0.9% Intravenous Fluid Solution


Normal Saline 0/9% is a intravenous fluid solution that provides maintenance and replacement of deficits of extracellular fluid. It is commonly used throughout the world as an infusion proving water for hydration for patients undergoing major surgery including renal transplantation. It may be added to or infused concurrently with blood components, or used as a diluent in the transfusion of packed erythrocytes.

The electrolyte composition of Normal saline is as follows:
Sodium chloride 4.5 g/L

For this clinical trial Normal Saline 0.9% will be used intraoperatively and postoperatively for 48 hours as the intravenous fluid solution for all patients undergoing cadaveric renal transplantation in our institution.

Doses:

The volume of Normal Saline will be delivered based on routine clinical care under the guidance of the anaesthetists and renal physician. The fluid will be commenced immediately after the induction of anaesthesia and before the first surgical incision and discontinued after 48 post operative hours.

Intraoperatively: Normal Saline will be given as per conventional anaesthesia practice with 10–30 mL/kg/hr to maintain mean arterial pressure (MAP) within 20% of baseline preoperative value.

Postoperative Management: Postoperatively as per renal unit protocols all patients will receive a maintenance infusion of Normal Saline. The rate of the study fluid replacement is determined by the urine output as a “urine chaser”. Each hour the previous hour’s urine output + 30 ml will be replaced with trial fluid. The “urine chaser” is commenced in the recovery room and continues for the first 24 hours. The treating medical staff may alter the rate of fluid administration as clinically required. Any additional fluid boluses of trial drug crystalloid solution may be administered to any patient if volume supplementation is required. For the next 24-hours (day 2) any further crystalloid infusion consists of the study fluid, with the rate of the crystalloid infusion being at the discretion of the treating medical staff. After 48 hours the study fluid is no longer used and the rate and type of any further crystalloid administration is at the discretion of the treating medical staff.
Control group
Active

Outcomes
Primary outcome [1] 286192 0
Standard base deficit as measured by a automated blood gas analyser
Timepoint [1] 286192 0
Mesaured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Primary outcome [2] 286193 0
Serum potassium
Timepoint [2] 286193 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Primary outcome [3] 286194 0
Serum creatinine
Timepoint [3] 286194 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively and then prior to hospsital discharge
Secondary outcome [1] 295336 0
Strong-ion-difference This is a quantitative physicochemical analysis using Stewart's quantitative equation: The formula used: measured SID, mEq/l =[Na+]+[K+]+[Mg2+]+Ca2+]-[Cl-]-[lactate]
Timepoint [1] 295336 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [2] 295337 0
Serum albumin. The anion concentrations for albumin will be calculated using Figge's formulae:

albumin anions, mEq/l =[albumin] X (0.123 X pH-0.631)
Timepoint [2] 295337 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [3] 295338 0
Serum phosphate. The anion concentrations for phosphate will be calculated using Figge's formulae:

phosphate anions, mEq/l =[phosphate] X (0.309 X pH-0.469)
Timepoint [3] 295338 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [4] 295339 0
Peak urine neutrophil gelatinase-associated lipocalin (NGAL)
Timepoint [4] 295339 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [5] 295342 0
Peak serum neutrophil gelatinase-associated lipocalin (NGAL)
Timepoint [5] 295342 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [6] 295343 0
Serum Cystatin C
Timepoint [6] 295343 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [7] 295344 0
Requirement for Renal Replacement Therapy
Timepoint [7] 295344 0
Measured immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [8] 295345 0
Duration of hospital stay in days
Timepoint [8] 295345 0
Postoperative period
Secondary outcome [9] 295346 0
Myocardial Infarction defined as ECG depression or elevation associated with myocardial enzyme elevation (cTropI>.06)
Timepoint [9] 295346 0
Duration of hospital stay
Secondary outcome [10] 295347 0
Pneumonia defined as elevated temperature and elevated white cell count with radiological confirmation
Timepoint [10] 295347 0
Duration of hospital stay
Secondary outcome [11] 295348 0
Cardiac arrythmias defined as ECG changes requiring medical treatment or cardioversion or heart rate <50beats/min requiring medical treatment/pacing
Timepoint [11] 295348 0
Duration of hospital stay
Secondary outcome [12] 295349 0
Pulmonary embolism defined as radiologically embolus confirmed with V:Q scan or Computed Tomography pulmonary angiogram
Timepoint [12] 295349 0
Duration of hospital stay
Secondary outcome [13] 295350 0
Urine output
Timepoint [13] 295350 0
Measured intraoperatively, immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
Secondary outcome [14] 295351 0
Heart failure defined as acute pulmonary oedema based on symptoms of heart failure associated with radiological features of pulmonary oedema/congestion or echocardiagrahic features of ventricular dysfunction
Timepoint [14] 295351 0
Duration of hospital stay
Secondary outcome [15] 295398 0
Postoperative death
Timepoint [15] 295398 0
Within 30 postoperative days

Eligibility
Key inclusion criteria
1. Adult patients (age > 18years)
2. Deceased donor renal transplantation (heart-beating or non heart-beating)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Preoperative hyperkalaemia (serum potassium > 6.0 mmol/L
2. Pregnancy
3. Chronic liver disease (liver function tests > 1.5 X normal value)
4. Known allergic reaction to study solutions
5. Combined liver-kidney transplantation

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be informed about the study and consented at the renal or pre-anaesthesia admission clinic at least 4 weeks prior to surgery. On the day of surgery, an independent anaesthetist or research nurse who is not a study investigator will open a sealed opaque randomisation envelope.

Participants will be randomly assigned to one of two groups using a random number allocation system with permuted blocks. One group will receive the balanced crystalloid solution Plasmalyte (Baxter, Sydney, NSW) with anions as acetate, gluconate and chloride, the other group will receive Normal Saline 0.9% (Baxter, Sydney, NSW), with anions as chloride.

Study participants, surgeons, nephrologists, anaesthetists and all medical staff involved with the management of the patient throughout the study period will be blinded to treatment allocation.

This is a blinded clinical trial. Blinding of both Normal Saline and Plasmalyte solution will be done by Baxter Healthcare Australia. Fluids will be prepared in 1 litre clear plastic fluid container flasks (the exact same packaging that the fluids are normally prepared in), however there will be no labelling/writing on the container that would allow identification of the crystalloid fluid solution. Each 1-litre flask containing will have the following labelling
printed on the side:
1. Renal Transplant Fluid Trial Solution
2. Plasmalyte Solution or Normal Saline 0.9%
3. Expiry Date

Baxter Healthcare will compound the products in a strictly aseptic process. The shelf life of any of these solutions prepared under such aseptic conditions would be set at 360 days, when stored at <25C.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e., computerised sequence generation) will be preformed. For each patient, an opaque envelope containing the group assignment will be prepared, sealed and sequentially numbered. On the morning of surgery the anaesthetist will open the envelope and randomised the patients into one of the two groups described above.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1533 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 7371 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 284431 0
Hospital
Name [1] 284431 0
Austin Hospital
Address [1] 284431 0
Department of Anaesthesia
Studley Road, Heidelberg, Victoria, 3084
Country [1] 284431 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital, Department of Anaeasthesia
Address
Department of Anaesthesia
Studley Road, Heidelbeg, Victoria,3084
Country
Australia
Secondary sponsor category [1] 283354 0
None
Name [1] 283354 0
Address [1] 283354 0
Country [1] 283354 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286403 0
Austin Health Research Ethics Unit
Ethics committee address [1] 286403 0
Austin Health Research Ethics Unit
Henry Buck Building
Austin Hospital
Studley Road
Heidelberg, Victoria
3084
Ethics committee country [1] 286403 0
Australia
Date submitted for ethics approval [1] 286403 0
21/12/2011
Approval date [1] 286403 0
29/12/2011
Ethics approval number [1] 286403 0
0452

Summary
Brief summary
Background:
Fifty people die every day in Australia with kidney related disease with recent data from December 2009 showing that 1,105 of the 10,341 people receiving dialysis (11%) were on the renal transplant waiting list. Only about 6% receive a transplant each year and when patients present for transplantation, intravenous fluid therapy is critical to ensure optimal graft perfusion and function. Fluid therapy is important to maintain intravascular volume during and after
kidney transplantation whilst avoiding metabolic and electrolyte disturbances which may further compromise graft function. Traditionally normal saline (NS) or potassium-free fluids are the IV fluid therapy of choice in the perioperative period for patients undergoing kidney
transplantation. The rationale for using NS is the avoidance of the administration of large volumes of potassium which is present in small concentrations in Plasmalyte solution
(5mmol/L). The potassium contained in Plasmalyte solution may contribute to hyperkalemia although current evidence suggests that balanced fluid solutions may confer clinical benefits over NS as the administration of large volumes of NS has been strongly associated with the development of hyperchloremic metabolic acidosis which in turn may cause hyperkalemia through an extracellular shift of potassium.

Study rationale:
There are very few studies comparing the different types of crystalloid fluids that patients receive when undergoing renal transplantation. In order to prevent delayed graft function it is common for patients to receive 4 to 8 litres/day of crystalloid therapy per day to maintain sufficient intravascular volume. The commonest fluid used for patients undergoing renal transplantation at Austin Hospital is 0.9% Normal Saline, however its use is associated with severe metabolic disturbances.

There is emerging evidence that for patients undergoing renal transplantation who receive a balanced crystalloid instead of Normal Saline, there may be beneficial effects on the incidence of early allograft dysfunction and electrolyte disturbances.

Hypothesis: When used as crystalloid therapy for patients undergoing renal transplantation will the balanced crystalloid fluid Plasmalyte Solution, have more favourable effects on metabolic acidosis and early graft function compared to 0.9% Normal Saline.

Study design:
Single centre randomised controlled blinded study.

Inclusion criteria:
Adult patients (age > 18years) undergoing deceased donor renal transplantation (heart-beating
or non heart-beating).

Primary endpoint:
1. Standard base deficit immediately post surgery in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
2. Serum potassium levels in the Post Anaesthesia Care Unit and at 24 hours & 48 hrs postoperatively
3. Serum Creatinine

Secondary endpoints:
4. Strong-ion-difference
5. Serum Albumin
6. Serum Phosphate
7. Renal biomarkers including: serum and urine NGAL and Cystatin C
8. Requirement for Renal Replacement Therapy
9. Duration of Hospital Stay
10. Adverse events including myocardial infarction, pneumonia, cardiac arrythmias, pulmonary embolism, heart failure
11. Death within 30 postoperative days

No of participants: 50

Recruiting Hospital: Austin Hospital

Clinical significance:
A finding that Plasmalyte solution has more favourable effects on renal transplant associated acidosis, strong-ion difference, hyperkaleamia and delayed graft function may influence the fluid chosen for patients undergoing renal transplantation.
Trial website
Nil
Trial related presentations / publications
Presentation: (Late breaking abstract) The Effects of Normal Saline and an Acetate-Buffered Crystalloid Solution on Hyperkalemia in Deceased Donor Renal Transplantation: A Randomized Blinded Trial. American Society of Nephrology Annual Scientific Meeting. 3rd – 8th Nov, 2015, San Diego Convention Center, San Diego, USA (2015)
Public notes

Contacts
Principal investigator
Name 33566 0
Dr Laurence Weinberg
Address 33566 0
Department of Anaesthesia
Studley Road
Heidelberg, 3084
Victoria, Australia
Country 33566 0
Australia
Phone 33566 0
+61 3 94965000
Fax 33566 0
Email 33566 0
Laurence.Weinberg@austin.org.au
Contact person for public queries
Name 16813 0
Dr Dr Laurence Weinberg
Address 16813 0
Department of Anaesthesia
Austin Hospital
Studley Road
Heidelberg, 3084, Victoria
Country 16813 0
Australia
Phone 16813 0
+61 3 94965000
Fax 16813 0
+61 3 94596421
Email 16813 0
Laurence.Weinberg@austin.org.au
Contact person for scientific queries
Name 7741 0
Dr Dr Laurence Weinberg
Address 7741 0
Department of Anaesthesia
Austin Hospital
Studley Road
Heidelberg, 3084, Victoria
Country 7741 0
Australia
Phone 7741 0
+61 3 94965000
Fax 7741 0
+61 3 94596421
Email 7741 0
Laurence.Weinberg@austin.org.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary