Sodium Bicarbonate in Cardiac Surgery Study (Bic-MC)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Cardiac Surgery Cardiopulmonary Bypass |
Drug: Sodium Bicarbonate Drug: Sodium Chloride |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| 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 |
- 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. ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Change in serum creatinine from baseline to peak level after adjustment for relevant baseline characteristics [ Time Frame: within first two-five postoperative days ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Change in serum urea from baseline to peak [ Time Frame: within first two-five postoperative days ] [ Designated as safety issue: No ]
- Change in NGAL from baseline to peak [ Time Frame: within first 24 postoperatively ] [ Designated as safety issue: No ]
- Change in electrolyte status from baseline to peak [ Time Frame: within first 24-48hrs postoperatively ] [ Designated as safety issue: Yes ]
- Requirement of renal replacement therapy [ Time Frame: within first postoperative days ] [ Designated as safety issue: No ]
- Length of ventilation [ Time Frame: from commencement to end of intubation ] [ Designated as safety issue: No ]
- Length of stay in Intensive care [ Time Frame: from admission to discharge from Intensive care ] [ Designated as safety issue: No ]
- Length of stay in hospital [ Time Frame: from admission to discharge from hospital ] [ Designated as safety issue: No ]
- Hospital-Mortality [ Time Frame: during hospital stay ] [ Designated as safety issue: No ]
- 90-day mortality [ Time Frame: during 90 days postoperatively ] [ Designated as safety issue: No ]
- COMT polymorphism [ Time Frame: sampling at induction of anesthesia ] [ Designated as safety issue: No ]
| Enrollment: | 350 |
| Study Start Date: | May 2008 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
Drug: 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).
Other Name: hyeprtonic sodium chloride
|
|
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
|
Drug: 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).
Other Name: Hypertonic bicarbonate
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
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
Contacts and Locations| Australia, Victoria | |
| Austin Health | |
| Melbourne, Victoria, Australia, 3084 | |
| Canada, Alberta | |
| University of Alberta | |
| Edmonton, Alberta, Canada, T6G 2B7 | |
| Germany | |
| Charité University Medicine | |
| Berlin, Germany, 13353 | |
| Ireland | |
| University Clinic Dublin, School of Medicine and Medical Science | |
| Dublin, Ireland | |
| Study Chair: | Rinaldo Bellomo, MD, FRACP | Austin Health, Melbourne, Australia |
| Principal Investigator: | Michael Haase, MD | Charité University Medicine Berlin, Germany |
| Principal Investigator: | Sean M Bagshaw, MD | University of Alberta, Edmonton, Canada |
| Principal Investigator: | Patrick Murray, MD | University Clinic Dublin, Dublin, Ireland |
More Information
No publications provided
| Responsible Party: | Rinaldo Bellomo, Director of ICU research, Austin Health |
| ClinicalTrials.gov Identifier: | NCT00672334 History of Changes |
| Other Study ID Numbers: | EudraCT 2007-002223-32 |
| Study First Received: | May 1, 2008 |
| Last Updated: | July 31, 2012 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Austin Health:
|
Cardiac surgery Cardiopulmonary bypass Oxidative stress Acute renal dysfunction Sodium bicarbonate |
ClinicalTrials.gov processed this record on May 23, 2013