Cardiac SurgeryPhase 2/3Bic-MCNCT00672334
Sodium Bicarbonate in Cardiac Surgery Study
A Phase 2/3 study testing Sodium Bicarbonate and Sodium Chloride in people with Cardiac Surgery and Cardiopulmonary Bypass, run by Austin Health at 4 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery, Cardiopulmonary Bypass
- What is being tested?
- Sodium Bicarbonate and Sodium Chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 350 participants
- Where
- 4 sitesin 4 countries
- Study dates
- May 2008to Jan 2012
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 9Show fewer
- Insulin dependent diabetes mellitus
- Valve surgery (with or without coronary artery bypass graft)
- Redo cardiac surgery
Who cannot join
- 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
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Ireland1 site
University Clinic Dublin, School of Medicine and Medical Science
Dublin, Dublin
About this study
Official 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
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).
Read more
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.
Read the detailed description
Renal impairment following cardiopulmonary bypass is common. While most of these patients do not require either short or long term renal replacement, the mortality of patients with acute renal failure is substantially greater than those who do not develop renal dysfunction.
In a pilot double-blind, randomized controlled trial we 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.
There is evidence that sodium bicarbonate affects the cardiovascular, respiratory and immune systems and may be of benefit to patients undergoing cardiac surgery.
Study Design - overview and rationale Patients will be randomised to receive sodium bicarbonate from the induction of anaesthesia until 24 hours postoperatively, or a placebo (sodium chloride).
Serum creatinine is the most commonly used clinical indicator of renal function along with urine output. Both will be measured for several days postoperatively - the time period during which renal impairment is most likely to develop.
Randomisation The randomisation will be based on random numbers generated by computer. Once consent is obtained, the allocation of either treatment with sodium bicarbonate or placebo will be organised by an independent person (clinical trials pharmacist) who will dispense the coded and blinded infusion bags (shrink-wrapped in extra black plastic bags). This will be delivered to the anaesthetic staff looking after the patient in theatre, and the ICU nurse caring for the patient postoperatively.
20 ml samples of heparinised blood and urine will be taken from the arterial line or urine catheter. Samples will be taken immediately after the preoperative insertion of the arterial/urine catheter, at 6, 24, 48, 72, 96 and 120 hours after commencement of cardiopulmonary bypass. Immediately following collection, the preoperative, 6 and 24 hour blood and urine will be centrifuged at low speed to separate the plasma from the cellular components. Urine and plasma and full-blood (for COMT polymorphism) will be stored in aliquots (where necessary) at -70 degrees prior to batch analysis.
The following variables will be obtained:
Code for patient, gender and age. Date and time of admission to ICU Operative procedure and date and time on and off cardiopulmonary bypass Preoperative assessment of left ventricular function, Comorbidities, Pre-, intra- and post-operative medication, Markers of renal function and COMT polymorphism as described above, Doses of frusemide administered (or rate of frusemide infusion) Use of inotropes or vasopressors Cardiac output whenever measured for clinical purposes in the first 24 hours postoperatively Requirement of renal replacement therapy Urine output in each 6 hour period during the presence of urine catheter Acid base status and electrolytes at baseline, 6 and 24 hours after commencement of cardiopulmonary bypass, Time of intubation and extubation, Date and time of arrival on and discharge from ICU and hospital, death Resources required The principle of the study has been discussed with the involved cardiac anaesthetists, cardiac surgeons, intensivists and intensive care nurses, who have offered their co-operation. ICU research nurse to allocate patients and collect clinical data. Pharmacy will be required to prepare drug and placebo infusion bags. Clinical pathology will be required to perform 24 hour creatinine clearance estimation (in addition to those tests clinically indicated) Protocol violations All protocol violations will be recorded. It will then be decided whether the nature of such violation had been such that the patient should be excluded from primary data analysis. Such evaluation will be blinded to treatment.
Withdrawal The treating clinician will have the right to withdraw the patient from the study if he or she believes that continued participation is jeopardising the patient's well being.
Ethical Issues sodium bicarbonate used in this study is considered to be very safe as has been demonstrated by its widespread clinical use in the management of critically ill patients with metabolic acidosis. We consider the potential benefit of this treatment theoretically significant. Given the balance of benefits and risks, we consider it ethical to proceed and seek informed consent.
Indemnity This is an investigator-initiated study and, accordingly, no commercial sponsor's indemnity has been provided.
Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse. The clinical care of a patient who does not consent for any reason will not be affected.
- Conditions
- Cardiac Surgery, Cardiopulmonary Bypass
- Being tested
- Sodium Bicarbonate, Sodium Chloride
- Keywords
- Cardiac surgery, Cardiopulmonary bypass, Oxidative stress, Acute renal dysfunction, Sodium bicarbonate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium BicarbonateDrug
Also called Hypertonic 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).
Sodium ChlorideDrug
Also called hyeprtonic 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).
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | 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 Receives: Drug: Sodium Chloride |
| 1 | Experimental | 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 Receives: Drug: Sodium Bicarbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level after adjustment for relevant baseline characteristics
Measured: within first two-five postoperative days.
Secondary outcomes (15)
Proportion of patients developing an increase in serum creatinine greater than 50% from baseline to peak level after adjustment for relevant baseline characteristics
Measured: within first two-five postoperative days
Proportion of patients developing an increase in serum creatinine greater than 100% from baseline to peak level after adjustment for relevant baseline characteristics
Measured: within first two-five postoperative days
Change in serum creatinine from baseline to peak level after adjustment for relevant baseline characteristics
Measured: within first two-five postoperative days
Proportion of patients developing any of the RIFLE criteria: R, I or F after adjustment for relevant baseline characteristics
Measured: within first five postoperative days
Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition)after adjustment for relevant baseline characteristics
Measured: within 48 hours postoperatively
Change in serum urea from baseline to peak
Measured: within first two-five postoperative days
Change in NGAL from baseline to peak
Measured: within first 24 postoperatively
Change in electrolyte status from baseline to peak
Measured: within first 24-48hrs postoperatively
Requirement of renal replacement therapy
Measured: within first postoperative days
Length of ventilation
Measured: from commencement to end of intubation
Length of stay in Intensive care
Measured: from admission to discharge from Intensive care
Length of stay in hospital
Measured: from admission to discharge from hospital
Hospital-Mortality
Measured: during hospital stay
90-day mortality
Measured: during 90 days postoperatively
COMT polymorphism
Measured: sampling at induction of anesthesia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Austin Health
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Rinaldo Bellomo, Austin Health
- Investigators
- Rinaldo Bellomo, MD, FRACP, Study chair, Austin Health, Melbourne, AustraliaMichael Haase, MD, Principal investigator, Charité-University Medicine (Berlin, Germany)Sean M Bagshaw, MD, Principal investigator, University of Alberta, Edmonton, CanadaPatrick Murray, MD, Principal investigator, University Clinic Dublin, Dublin, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00672334
- Sponsor's protocol ID
- EudraCT 2007-002223-32
- Acronym
- Bic-MC
- Status last verified
- Jul 2012
- First submitted
- 1 May 2008
- Last updated
- 1 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Elitok S, Kuppe H, Devarajan P, Bellomo R, Isermann B, Westphal S, Kube J, Albert C, Ernst M, Kropf S, Haase-Fielitz A, Haase M. Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial. Anesth Analg. 2021 Dec 1;133(6):1510-1519. doi: 10.1213/ANE.0000000000005741.
PubMed 34543256Elitok S, Devarajan P, Bellomo R, Isermann B, Haase M, Haase-Fielitz A. NGAL/hepcidin-25 ratio and AKI subtypes in patients following cardiac surgery: a prospective observational study. J Nephrol. 2022 Mar;35(2):597-605. doi: 10.1007/s40620-021-01063-5. Epub 2021 May 24.
PubMed 34028701Haase M, Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Hannon C, Murray PT, Bailey MJ, Bellomo R, Bagshaw SM. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med. 2013;10(4):e1001426. doi: 10.1371/journal.pmed.1001426. Epub 2013 Apr 16.
PubMed 23610561Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Ostland V, Westphal S, Hoffmann J, Prowle J, Mertens PR, Westerman M, Bellomo R, Haase M. Low preoperative hepcidin concentration as a risk factor for mortality after cardiac surgery: a pilot study. J Thorac Cardiovasc Surg. 2013 May;145(5):1380-6. doi: 10.1016/j.jtcvs.2012.09.003. Epub 2012 Oct 9.
PubMed 23062413Haase-Fielitz A, Mertens PR, Plass M, Kuppe H, Hetzer R, Westerman M, Ostland V, Prowle JR, Bellomo R, Haase M. Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study. Crit Care. 2011 Aug 4;15(4):R186. doi: 10.1186/cc10339.
PubMed 21816077
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00672334
- Acronym / sponsor ID
- Bic-MC / EudraCT 2007-002223-32
- Conditions
- Cardiac Surgery, Cardiopulmonary Bypass
- Keywords
- Cardiac surgery, Cardiopulmonary bypass, Oxidative stress, Acute renal dysfunction, Sodium bicarbonate
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Austin HealthOther government
- Study start
- May 2008
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 6 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Renal impairment following cardiopulmonary bypass is common. While most of these patients do not require either short or long term renal replacement, the mortality of patients with acute renal failure is substantially greater than those who do not develop renal dysfunction.
In a pilot double-blind, randomized controlled trial we 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.
There is evidence that sodium bicarbonate affects the cardiovascular, respiratory and immune systems and may be of benefit to patients undergoing cardiac surgery.
Study Design - overview and rationale Patients will be randomised to receive sodium bicarbonate from the induction of anaesthesia until 24 hours postoperatively, or a placebo (sodium chloride).
Serum creatinine is the most commonly used clinical indicator of renal function along with urine output. Both will be measured for several days postoperatively - the time period during which renal impairment is most likely to develop.
Randomisation The randomisation will be based on random numbers generated by computer. Once consent is obtained, the allocation of either treatment with sodium bicarbonate or placebo will be organised by an independent person (clinical trials pharmacist) who will dispense the coded and blinded infusion bags (shrink-wrapped in extra black plastic bags). This will be delivered to the anaesthetic staff looking after the patient in theatre, and the ICU nurse caring for the patient postoperatively.
20 ml samples of heparinised blood and urine will be taken from the arterial line or urine catheter. Samples will be taken immediately after the preoperative insertion of the arterial/urine catheter, at 6, 24, 48, 72, 96 and 120 hours after commencement of cardiopulmonary bypass. Immediately following collection, the preoperative, 6 and 24 hour blood and urine will be centrifuged at low speed to separate the plasma from the cellular components. Urine and plasma and full-blood (for COMT polymorphism) will be stored in aliquots (where necessary) at -70 degrees prior to batch analysis.
The following variables will be obtained:
Code for patient, gender and age. Date and time of admission to ICU Operative procedure and date and time on and off cardiopulmonary bypass Preoperative assessment of left ventricular function, Comorbidities, Pre-, intra- and post-operative medication, Markers of renal function and COMT polymorphism as described above, Doses of frusemide administered (or rate of frusemide infusion) Use of inotropes or vasopressors Cardiac output whenever measured for clinical purposes in the first 24 hours postoperatively Requirement of renal replacement therapy Urine output in each 6 hour period during the presence of urine catheter Acid base status and electrolytes at baseline, 6 and 24 hours after commencement of cardiopulmonary bypass, Time of intubation and extubation, Date and time of arrival on and discharge from ICU and hospital, death Resources required The principle of the study has been discussed with the involved cardiac anaesthetists, cardiac surgeons, intensivists and intensive care nurses, who have offered their co-operation. ICU research nurse to allocate patients and collect clinical data. Pharmacy will be required to prepare drug and placebo infusion bags. Clinical pathology will be required to perform 24 hour creatinine clearance estimation (in addition to those tests clinically indicated) Protocol violations All protocol violations will be recorded. It will then be decided whether the nature of such violation had been such that the patient should be excluded from primary data analysis. Such evaluation will be blinded to treatment.
Withdrawal The treating clinician will have the right to withdraw the patient from the study if he or she believes that continued participation is jeopardising the patient's well being.
Ethical Issues sodium bicarbonate used in this study is considered to be very safe as has been demonstrated by its widespread clinical use in the management of critically ill patients with metabolic acidosis. We consider the potential benefit of this treatment theoretically significant. Given the balance of benefits and risks, we consider it ethical to proceed and seek informed consent.
Indemnity This is an investigator-initiated study and, accordingly, no commercial sponsor's indemnity has been provided.
Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse. The clinical care of a patient who does not consent for any reason will not be affected.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Drug: Sodium Chloridesodium 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 |
| 1 | Experimental | Drug: Sodium BicarbonateThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium BicarbonateAlso: Hypertonic bicarbonateIn 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). | Drug | 1 |
| Sodium ChlorideAlso: hyeprtonic sodium chlorideIn 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). | Drug | 2 |
Primary outcome
Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level after adjustment for relevant baseline characteristics
Time frame: within first two-five postoperative days.
15 secondary outcomes
Proportion of patients developing an increase in serum creatinine greater than 50% from baseline to peak level after adjustment for relevant baseline characteristics
Time frame: within first two-five postoperative days
Proportion of patients developing an increase in serum creatinine greater than 100% from baseline to peak level after adjustment for relevant baseline characteristics
Time frame: within first two-five postoperative days
Change in serum creatinine from baseline to peak level after adjustment for relevant baseline characteristics
Time frame: within first two-five postoperative days
Proportion of patients developing any of the RIFLE criteria: R, I or F after adjustment for relevant baseline characteristics
Time frame: within first five postoperative days
Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition)after adjustment for relevant baseline characteristics
Time frame: within 48 hours postoperatively
Change in serum urea from baseline to peak
Time frame: within first two-five postoperative days
Change in NGAL from baseline to peak
Time frame: within first 24 postoperatively
Change in electrolyte status from baseline to peak
Time frame: within first 24-48hrs postoperatively
Requirement of renal replacement therapy
Time frame: within first postoperative days
Length of ventilation
Time frame: from commencement to end of intubation
Length of stay in Intensive care
Time frame: from admission to discharge from Intensive care
Length of stay in hospital
Time frame: from admission to discharge from hospital
Hospital-Mortality
Time frame: during hospital stay
90-day mortality
Time frame: during 90 days postoperatively
COMT polymorphism
Time frame: sampling at induction of anesthesia
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2012.
- Derived from this study: PubMed 34543256Elitok S, Kuppe H, Devarajan P, Bellomo R, Isermann B, Westphal S, Kube J, Albert C, Ernst M, Kropf S, Haase-Fielitz A, Haase M. Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial. Anesth Analg. 2021 Dec 1;133(6):1510-1519. doi: 10.1213/ANE.0000000000005741.
- Derived from this study: PubMed 34028701Elitok S, Devarajan P, Bellomo R, Isermann B, Haase M, Haase-Fielitz A. NGAL/hepcidin-25 ratio and AKI subtypes in patients following cardiac surgery: a prospective observational study. J Nephrol. 2022 Mar;35(2):597-605. doi: 10.1007/s40620-021-01063-5. Epub 2021 May 24.
- Derived from this study: PubMed 23610561Haase M, Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Hannon C, Murray PT, Bailey MJ, Bellomo R, Bagshaw SM. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med. 2013;10(4):e1001426. doi: 10.1371/journal.pmed.1001426. Epub 2013 Apr 16.
- Derived from this study: PubMed 23062413Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Ostland V, Westphal S, Hoffmann J, Prowle J, Mertens PR, Westerman M, Bellomo R, Haase M. Low preoperative hepcidin concentration as a risk factor for mortality after cardiac surgery: a pilot study. J Thorac Cardiovasc Surg. 2013 May;145(5):1380-6. doi: 10.1016/j.jtcvs.2012.09.003. Epub 2012 Oct 9.
- Derived from this study: PubMed 21816077Haase-Fielitz A, Mertens PR, Plass M, Kuppe H, Hetzer R, Westerman M, Ostland V, Prowle JR, Bellomo R, Haase M. Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study. Crit Care. 2011 Aug 4;15(4):R186. doi: 10.1186/cc10339.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rinaldo Bellomo, MD, FRACP study chair
Austin Health, Melbourne, Australia
Michael Haase, MD principal investigator
Charité-University Medicine (Berlin, Germany)
Sean M Bagshaw, MD principal investigator
University of Alberta, Edmonton, Canada
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sodium Bicarbonate and Sodium Chloride in people with Cardiac Surgery and Cardiopulmonary Bypass, run by Austin Health at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, Canada, Germany, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level after adjustment for relevant baseline characteristics (time frame: within first two-five postoperative days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00672334, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2012.