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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00878956




Registration number
NCT00878956
Ethics application status
Date submitted
8/04/2009
Date registered
9/04/2009
Date last updated
1/08/2012

Titles & IDs
Public title
Bicarbonate in Cardiac Surgery
Scientific title
A Phase IIb Multiple Blind Randomized Controlled Trial of Sodium Bicarbonate in Cardiac Surgery at High-risk of Acute Kidney Injury
Secondary ID [1] 0 0
H2007/02808
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Injuries and Accidents 0 0 0 0
Other injuries and accidents

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

Active comparator: 1 - 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).

Placebo comparator: 2 - 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).


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 greater than 25% or 44 mmol/L (0.5 mg/dL) postoperative increase in serum creatinine after adjustment for relevant baseline variables
Timepoint [1] 0 0
within first five postoperative days
Secondary outcome [1] 0 0
Mean changes in serum creatinine after adjustment for relevant baseline variables
Timepoint [1] 0 0
within first five postoperative days
Secondary outcome [2] 0 0
mean changes in serum cystatin C after adjustment for relevant baseline variables
Timepoint [2] 0 0
within first five postoperative days
Secondary outcome [3] 0 0
mean changes in urinary neutrophil gelatinase-associated lipocalin (NGAL)after adjustment for relevant baseline variables
Timepoint [3] 0 0
within first five postoperative days
Secondary outcome [4] 0 0
Duration of ventilation
Timepoint [4] 0 0
Until time of extubation from mechanical ventilation
Secondary outcome [5] 0 0
Proportion of patients developing any of the RIFLE criteria: R, I or F
Timepoint [5] 0 0
within first five postoperative days
Secondary outcome [6] 0 0
Incidence of post-operative atrial fibrillation
Timepoint [6] 0 0
within first five postoperative days
Secondary outcome [7] 0 0
Duration of stay in the intensive care unit (ICU)
Timepoint [7] 0 0
from admission to the ICU
Secondary outcome [8] 0 0
Duration of stay in hospital
Timepoint [8] 0 0
from admission to discharge from hospital
Secondary outcome [9] 0 0
90-day mortality
Timepoint [9] 0 0
during 90 days postoperatively
Secondary outcome [10] 0 0
Change in electrolyte status from baseline to peak
Timepoint [10] 0 0
within first 24-48hrs postoperatively

Eligibility
Key inclusion criteria
* Age above 70 years
* Pre-existing renal impairment (preoperative plasma creatinine concentration > 1.4 mg/dL
* New York Heart Association class III/IV or impaired left ventricular function (left ventricular ejection fraction < 50%)
* Valvular surgery or concomitant valvular and coronary artery bypass graft surgery
* Redo cardiac surgery
* Insulin-dependent diabetes mellitus
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* End stage renal disease (plasma creatinine concentration > 3.4 mg/dL)
* Emergency cardiac surgery
* Planned off-pump cardiac surgery
* Known blood-borne infectious disease
* Chronic inflammatory disease on immunosuppression
* Chronic moderate to high dose corticosteroid therapy (> 10 mg/d prednisone or equivalent)
* Enrolled in conflicting research study
* Age < 18 years

Study design
Purpose of the study
Treatment
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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2012
Sample size
Target
Accrual to date
Final
427
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Hospital - Melbourne
Recruitment hospital [2] 0 0
Warringal Private Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Government body
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). 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/study/NCT00878956
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rinaldo Bellomo, MD, FRACP
Address 0 0
Austin Hospital, 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/study/NCT00878956