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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/NCT00672334




Registration number
NCT00672334
Ethics application status
Date submitted
1/05/2008
Date registered
6/05/2008
Date last updated
1/08/2012

Titles & IDs
Public title
Sodium Bicarbonate in Cardiac Surgery Study
Scientific title
A Multicenter, Randomized, Double Blind, Placebo Controlled Study of the Effect of Sodium Bicarbonate on Postoperative Renal Function in Patients Undergoing Elective Cardiopulmonary Bypass
Secondary ID [1] 0 0
EudraCT 2007-002223-32
Universal Trial Number (UTN)
Trial acronym
Bic-MC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Surgery 0 0
Cardiopulmonary Bypass 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sodium Bicarbonate
Treatment: Drugs - Sodium Chloride

Placebo Comparator: 2 - sodium chloride at 0.5 mmol/kg loading pre-induction and then at 0.2 mmol/kg/hr over 24 hours after induction until the next day

Experimental: 1 - The active intervention is loading (05. mmol/kg) pre-surgery and continuous infusion of bicarbonate at 0.2 mmol/kg/hr for 24 hours after induction


Treatment: Drugs: Sodium Bicarbonate
In all patients body weight adjusted dose of study medication will be achieved by infusion of sodium bicarbonate at a dose of 0.5 mmol/kg body weight (=bolus) diluted in 250 mL over 1 hour immediately after the induction of anesthesia, prior to the first surgical incision followed by continuous intravenous infusion of 0.2 mmol/kg/hr (=maintenance) diluted in 1000 mL 23 hours (total dose of 5 mmol/kg over 24 hours).

Treatment: Drugs: Sodium Chloride
In all patients body weight adjusted dose of study medication will be achieved by infusion of sodium chloride at a dose of 0.5 mmol/kg body weight (=bolus) diluted in 250 mL over 1 hour immediately after the induction of anesthesia, prior to the first surgical incision followed by continuous intravenous infusion of 0.2 mmol/kg/hr (=maintenance) diluted in 1000 mL 23 hours (total dose of 5 mmol/kg over 24 hours).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level after adjustment for relevant baseline characteristics
Timepoint [1] 0 0
within first two-five postoperative days.
Secondary outcome [1] 0 0
Proportion of patients developing an increase in serum creatinine greater than 50% from baseline to peak level after adjustment for relevant baseline characteristics
Timepoint [1] 0 0
within first two-five postoperative days
Secondary outcome [2] 0 0
Proportion of patients developing an increase in serum creatinine greater than 100% from baseline to peak level after adjustment for relevant baseline characteristics
Timepoint [2] 0 0
within first two-five postoperative days
Secondary outcome [3] 0 0
Change in serum creatinine from baseline to peak level after adjustment for relevant baseline characteristics
Timepoint [3] 0 0
within first two-five postoperative days
Secondary outcome [4] 0 0
Proportion of patients developing any of the RIFLE criteria: R, I or F after adjustment for relevant baseline characteristics
Timepoint [4] 0 0
within first five postoperative days
Secondary outcome [5] 0 0
Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition)after adjustment for relevant baseline characteristics
Timepoint [5] 0 0
within 48 hours postoperatively
Secondary outcome [6] 0 0
Change in serum urea from baseline to peak
Timepoint [6] 0 0
within first two-five postoperative days
Secondary outcome [7] 0 0
Change in NGAL from baseline to peak
Timepoint [7] 0 0
within first 24 postoperatively
Secondary outcome [8] 0 0
Change in electrolyte status from baseline to peak
Timepoint [8] 0 0
within first 24-48hrs postoperatively
Secondary outcome [9] 0 0
Requirement of renal replacement therapy
Timepoint [9] 0 0
within first postoperative days
Secondary outcome [10] 0 0
Length of ventilation
Timepoint [10] 0 0
from commencement to end of intubation
Secondary outcome [11] 0 0
Length of stay in Intensive care
Timepoint [11] 0 0
from admission to discharge from Intensive care
Secondary outcome [12] 0 0
Length of stay in hospital
Timepoint [12] 0 0
from admission to discharge from hospital
Secondary outcome [13] 0 0
Hospital-Mortality
Timepoint [13] 0 0
during hospital stay
Secondary outcome [14] 0 0
90-day mortality
Timepoint [14] 0 0
during 90 days postoperatively
Secondary outcome [15] 0 0
COMT polymorphism
Timepoint [15] 0 0
sampling at induction of anesthesia

Eligibility
Key inclusion criteria
- Cardiac surgical patients in whom the use of cardiopulmonary bypass was planned and:

- Written informed consent of patient

- Age >18 years

- And having at least one ore more of the following risk factors for postoperative AKI:

- Age =/>70 years

- Preoperative plasma creatinine >120 µmol/L New York Heart Association class III /
IV or LVEF <35%

- Insulin dependent diabetes mellitus

- Valve surgery (with or without coronary artery bypass graft)

- Redo cardiac surgery
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Cardiac surgical patients will not be considered eligible if:

- An emergency operation is indicated (within 24 hours after hospital admission or on
intra-aortic balloon pump) or

- Pregnancy is confirmed or breastfeeding is present or

- A renal allograft is present or

- Preoperative acute renal failure within 6 weeks (acute rise in serum creatinine >50%
from baseline) is present or

- Pre-operative end stage renal disease (serum creatinine >300 µmol/L) is present or

- Chronic moderate to high dose corticosteroid therapy (>10 mg/d prednisone or
equivalent) is present

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2012
Sample size
Target
Accrual to date
Final
350
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Germany
State/province [2] 0 0
Berlin
Country [3] 0 0
Ireland
State/province [3] 0 0
Dublin

Funding & Sponsors
Primary sponsor type
Other
Name
Austin Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
With over one million operations a year, cardiac surgery with cardiopulmonary bypass is one
of the most common major surgical procedures worldwide (1). Acute kidney injury is a common
and serious postoperative complication of cardiopulmonary bypass and may affect 25% to 50% of
patients (2-4). Acute kidney injury carries significant costs (4) and is independently
associated with increased morbidity and mortality (2,3). Even minimal increments in plasma
creatinine are associated with an increase in mortality (5,6).

Multiple causes of cardiopulmonary bypass-associated acute kidney injury have been proposed,
including ischemia-reperfusion, generation of reactive oxygen species, hemolysis and
activation of inflammatory pathways (7-10). COMT LL genotype appears to increase the risk of
vasodilatory shock and AKI after cardiac surgery. To date, no simple, safe and effective
intervention to prevent cardiopulmonary bypass-associated acute kidney injury in a broad
patient population has been found (11-14).

Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by
cardiopulmonary bypass (10,15). Activation of complement during cardiac surgery (16) may also
participate in kidney injury. Urinary alkalinization may protect from kidney injury induced
by oxidant substances, iron-mediated free radical pathways, complement activation and tubular
hemoglobin cast formation (9,17,18). Of note, increasing urinary pH - in combination with
N-acetylcysteine (19,20) or without (21) - has recently been reported to attenuate acute
kidney injury in patients undergoing contrast-media infusion.

In a pilot double-blind, randomized controlled trial the investigators found sodium
bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now
need to be confirmed or refuted by further clinical investigations in other geographic and
institutional settings.

Accordingly, the investigators hypothesized that urinary alkalinization might protect kidney
function in patients at increased risk of acute kidney injury undergoing cardiopulmonary
bypass needs to be confirmed in an international multicenter, double-blind, randomized
controlled trial of intravenous sodium bicarbonate.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00672334
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rinaldo Bellomo, MD, FRACP
Address 0 0
Austin Health, Melbourne, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00672334