Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611001290987
Ethics application status
Approved
Date submitted
16/12/2011
Date registered
16/12/2011
Date last updated
18/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Sodium Bicarbonate for kidney protection in patients undergoing liver transplantation
Scientific title
Sodium Bicarbonate To Prevent Increases in Serum Creatinine After Orthotopic Liver Transplantation: a Pilot Double-Blind, Randomized Controlled Trial.
Secondary ID [1] 279620 0
Nil
Universal Trial Number (UTN)
U1111-1126-4906
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver transplantation 285414 0
Acute Kidney Injury 285415 0
Condition category
Condition code
Anaesthesiology 285595 285595 0 0
Anaesthetics
Surgery 285596 285596 0 0
Other surgery
Renal and Urogenital 285597 285597 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sodium Bicarbonate 8.4%

At our institution, sodium bicarbonate is presented in glass bottles of 100 mL, each containing 100 mmol of an 8.4% sodium bicarbonate solution. The concentration of the 8.4% bicarbonate solution is 2000 mOsm/kg. This 8.4% solution is a molar solution and therefore contains 1 mmol of HC03- per each ml.

Loading dose: A loading dose of 0.5 ml/kg (equivalent to 0.5 mmol/kg Sodium Bicarbonate 8.4%) will be administered over 1 hour, commencing immediately after the induction of anaesthesia and before the first surgical incision.

Maintenance dose: A continuous maintenance infusion will then be delivered at 0.15 ml/kg/hr (equivalent to 0.15 mmol/kg/hr Sodium Bicarbonate 8.4%) infused over the course of the surgery and discontinued at the completion of surgery at skin closure.

The loading dose and infusion will be into a central venous catheter (that is routinely inserted for this procedure) via a computerised syringe pump or volumetric infusion pump.

Dosing example: a 70kg patient will receive a loading dose of 0.5 mmol/kg, which is 35 mmol, or 35 ml of the 8.4% sodium bicarbonate solution. This will be followed by a continuous infusion of 0.15 mmol/kg/hr, which is 10.5 mmol per hour, or 10.5 ml per hour of the 8.4% sodium bicarbonate solution.
Intervention code [1] 283902 0
Prevention
Comparator / control treatment
Normal Saline 0.9%

Loading dose: A loading dose of 0.5 ml/kg Normal Saline 0.9% will be administered over 1 hour, commencing immediately after the induction of anaesthesia and before the first surgical incision.

Maintenance dose: A continuous maintenance infusion will then be delivered at 0.15 ml/kg/hr Normal saline 0.9% infused over the course of the surgery and discontinued at the completion of surgery at skin closure.

The loading dose and infusion will be into a central venous catheter (that is routinely inserted for this procedure) via a computerised syringe pump or volumetric infusion pump.

Dosing example: a 70kg patient will receive a loading dose of 0.5 mmol/kg or 35 ml of Normal saline 0.9% followed by a continuous infusion of 0.15 ml/kg/hr Normal Saline 0.9% which is 10.5 ml per hour of Normal Saline 0.9%
Control group
Placebo

Outcomes
Primary outcome [1] 286160 0
Serum creatinine
Timepoint [1] 286160 0
Immediately postoperatively, then 24 hours and 72 hours postoperatively
Primary outcome [2] 286161 0
Glomerular Filtration Rate (GFR)
Timepoint [2] 286161 0
Immediately postoperatively, then 24 hours and 72 hours postoperatively
Secondary outcome [1] 295266 0
Peak urine neutrophil gelatinase-associated lipocalin (NGAL)
Timepoint [1] 295266 0
Immediately postoperatively, then 24 hours and 72 hours postoperatively
Secondary outcome [2] 295267 0
Serum Cystatin C
Timepoint [2] 295267 0
Immediately postoperatively, then 24 hours and 72 hours postoperatively
Secondary outcome [3] 295268 0
Serum neutrophil gelatinase-associated lipocalin (NGAL)
Timepoint [3] 295268 0
Immediately postoperatively, then 24 hours and 72 hours postoperatively
Secondary outcome [4] 295269 0
Requirement for Renal Replacement Therapy
Timepoint [4] 295269 0
Immediately postoperatively until hospital discharge
Secondary outcome [5] 295270 0
Acid-base status (pH, standard Base Excess, serum bicarbonate)
Timepoint [5] 295270 0
Immediately postoperatively, then 24 hours and 72 hours postoperatively
Secondary outcome [6] 295271 0
Duration of ICU stay in hours
Timepoint [6] 295271 0
Postoperative period
Secondary outcome [7] 295272 0
Duration of hospital stay in days
Timepoint [7] 295272 0
Postoperative period
Secondary outcome [8] 295274 0
Myocardial Infarction defined as ECG depression or elevation associated with myocardial enzyme elevation (cTropI>.06)
Timepoint [8] 295274 0
Duration of hospital stay
Secondary outcome [9] 295275 0
Pneumonia defined as elevated temperature and elevated white cell count with radiological confirmation
Timepoint [9] 295275 0
Duration of hospital stay
Secondary outcome [10] 295276 0
Wound infection defined as surgical evacuation of pus or haematoma/secondary suture infection requiring antibiotic therapy
Timepoint [10] 295276 0
Duration of hospital stay
Secondary outcome [11] 295277 0
Cardiac arrythmias defined as ECG changes requiring medical treatment or cardioversion or heart rate <50beats/min requiring medical treatment/pacing
Timepoint [11] 295277 0
Duration of hospital stay
Secondary outcome [12] 295278 0
Pulmonary embolism defined as radiologically embolus confirmed with V:Q scan or Computed Tomography pulmonary angiogram
Timepoint [12] 295278 0
Duration of hospital stay
Secondary outcome [13] 295279 0
Mortality
Timepoint [13] 295279 0
Postoperative death within 30 days
Secondary outcome [14] 295280 0
Cerebral vascular event defined as new intracranial abnormality confirmed on Computed Tomography or Magnetic Resonance Imaging (MRI)
Timepoint [14] 295280 0
Duration of hospital stay
Secondary outcome [15] 295281 0
Hypernatremia ([Na ]>150mmol/L)
Timepoint [15] 295281 0
Duration of hospital stay
Secondary outcome [16] 295282 0
Hypokalemia ([K ] <3.5 mmol/L
Timepoint [16] 295282 0
Duration of hospital stay

Eligibility
Key inclusion criteria
Adult patients undergoing orthotopic liver transplantation
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. End stage renal disease (plasma creatinine >300 mmol/L)
2. Preoperative renal replacement therapy
3. Intraoperative continuous veno-veno haemofiltration
4. Combined liver-kidney transplant
5. Fulminant hepatic failure
6. Congestive cardiac failure
7. Preoperative hypernatraemia (serum sodium > 150 mmol/L)
8. Preoperative hyponatraemia (serum sodium < 130 mmol/L) concerns with central pontine myelinosis from additional Sodium load from study solution.
9. Preoperative hypokalaemia (serum potassium < 3.0 mmol/L)
10. Informed consent not obtained
11. Pregnancy

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 preanaesthesia admission clinic 1-2 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. The independent anaesthetist or research nurse will prepare either the Trial Solutions of Sodium Bicarbonate (8.4%) or Normal Saline (0.9%) in eight 50 mls syringes for the intraoperative loading dose and infusion. The syringes will be labeled Trial Drug Infusion ("Normal Saline 0.9% or Sodium Bicarbonate 8.4%) with coloured printed labels.
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
N/A
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/11/2010
Actual
28/11/2010
Date of last participant enrolment
Anticipated
28/11/2012
Actual
30/11/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 284395 0
Hospital
Name [1] 284395 0
Austin Hospital Department of Anaesthesia Research Fund
Country [1] 284395 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Department of Anaesthesia
Austin Hospital
Studley Road, Heidelberg
3084
Victoria
Country
Australia
Secondary sponsor category [1] 283324 0
None
Name [1] 283324 0
Address [1] 283324 0
Country [1] 283324 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286355 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 286355 0
Henry Buck Building
145 Studley Road
Austin Hospital
Studley Road, Heidelberg
3084
Victoria
Ethics committee country [1] 286355 0
Australia
Date submitted for ethics approval [1] 286355 0
Approval date [1] 286355 0
18/08/2010
Ethics approval number [1] 286355 0
H2010/03953

Summary
Brief summary
Acute renal failure is a common and serious postoperative complication of orthotopic liver transplantation. The reported incidence ranges from 17% to 95% and severe renal failure requiring renal replacement therapy occurs in 5% - 35% of patients after transplantation. Renal failure requiring haemodialysis post liver transplant, irrespective of pre-transplant dialysis status, is a profound risk factor for death. Identifying the risk factors for renal dysfunction after liver transplantation and developing therapeutic approaches to prevent, halt, or ameliorate de novo renal dysfunction or retard the progression of preexisting renal dysfunction should be fundamental goals in managing these patients.

Sodium bicarbonate is a drug in common use for the prevention of contrast nephropathy and has been shown to be effective in preventing acute kidney injury in patients undergoing cardiac surgery. It is used to effectively treat severe metabolic acidosis in critically ill patients. It is possible that sodium bicarbonate might reduce the oxidative stress which occurs during liver transplantation and so decrease or prevent acute kidney injury in these patients.

This is an investigator initiated, pilot, double-blind, randomized controlled trial. The purpose of this study is to determine whether administration of sodium bicarbonate reduces the risk of kidney injury, and also reduces some of the cellular changes and oxidative stress known to cause kidney injury after orthotopic liver transplantation. Adult patients undergoing orthotopic liver transplanation will be randomized to receive either sodium bicarbonate or placebo for the duration surgery.

Primary outcome: a rise in the serum creatinine to > 1.5 times the baseline value or decreased GFR > 25% (RIFLE class ‘R’) measured 72 hours postoperatively.

Secondary outcomes: To examine changes in peak serum and urinary NGAL and peak serum cystatin C (sensitive biomarkers of acute renal injury) compared to baseline, peak changes in delta creatinine, acid– base status.

Other outcomes collected will include duration of ICU stay, duration of hospital stay, all adverse events including institution of renal replacement therapy and hospital mortality.

Recruiting hospitals: Austin Hospital

Number of participants planned: 60
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33544 0
Dr Laurence Weinberg
Address 33544 0
Department of Anaesthesia, Austin Hospital Studley Rd, Heidelberg Victoria, 3084, Australia
Country 33544 0
Australia
Phone 33544 0
+61394965000
Fax 33544 0
Email 33544 0
Laurence.weinberg@austin.org.au
Contact person for public queries
Name 16791 0
Dr Laurence Weinberg
Address 16791 0
Department of Anaesthesia, Austin Hospital
Studley Rd, Heidelberg
Victoria, 3084, Australia
Country 16791 0
Australia
Phone 16791 0
+61 3 9496-5000
Fax 16791 0
+61 3 9459-6421
Email 16791 0
Laurence.Weinberg@austin.org.au
Contact person for scientific queries
Name 7719 0
Dr Laurence Weinberg
Address 7719 0
Department of Anaesthesia, Austin Hospital
Studley Rd, Heidelberg
Victoria, 3084, Australia
Country 7719 0
Australia
Phone 7719 0
+61 3 9496-5000
Fax 7719 0
+61 3 9459-6421
Email 7719 0
Laurence.Weinberg@austin.org.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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