Bicarbonate in Cardiac Surgery

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Rinaldo Bellomo, Austin Health
ClinicalTrials.gov Identifier:
NCT00878956
First received: April 8, 2009
Last updated: July 31, 2012
Last verified: July 2012
  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). 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
Acute Kidney Injury
Drug: Sodium Bicarbonate
Drug: Sodium Chloride
Phase 2

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: Treatment
Official Title: A Phase IIb Multiple Blind Randomized Controlled Trial of Sodium Bicarbonate in Cardiac Surgery at High-risk of Acute Kidney Injury

Resource links provided by NLM:


Further study details as provided by Austin Health:

Primary Outcome Measures:
  • 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 [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean changes in serum creatinine after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
  • mean changes in serum cystatin C after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
  • mean changes in urinary neutrophil gelatinase-associated lipocalin (NGAL)after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
  • Duration of ventilation [ Time Frame: Until time of extubation from mechanical ventilation ] [ Designated as safety issue: No ]
  • Proportion of patients developing any of the RIFLE criteria: R, I or F [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
  • Incidence of post-operative atrial fibrillation [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
  • Duration of stay in the intensive care unit (ICU) [ Time Frame: from admission to the ICU ] [ Designated as safety issue: No ]
  • Duration of stay in hospital [ Time Frame: from admission to discharge from hospital ] [ Designated as safety issue: No ]
  • 90-day mortality [ Time Frame: during 90 days 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 ]

Enrollment: 427
Study Start Date: April 2009
Study Completion Date: January 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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).
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).
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).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878956

Locations
Australia, Victoria
Austin Hospital
Melbourne, Victoria, Australia, 3084
Warringal Private Hospital
Melbourne, Victoria, Australia, 3084
New Zealand
Auckland City Hospital
Auckland, New Zealand
Waikato Hospital
Hamilton, New Zealand
Sponsors and Collaborators
Austin Health
Investigators
Principal Investigator: Rinaldo Bellomo, MD, FRACP Austin Hospital, Melbourne Australia
Study Chair: Frank van Haren, MD Waikato Hospital, Hamilton, New Zealand
Study Chair: Shay McGuinness, MB ChB, FRCA, FANZCA Auckland City Hospital, New Zealand
  More Information

No publications provided

Responsible Party: Rinaldo Bellomo, Director of ICU Research, Austin Health
ClinicalTrials.gov Identifier: NCT00878956     History of Changes
Other Study ID Numbers: H2007/02808
Study First Received: April 8, 2009
Last Updated: July 31, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:
Cardiac surgery
Cardiopulmonary bypass
Oxidative stress
Acute renal dysfunction
Sodium bicarbonate

Additional relevant MeSH terms:
Acute Kidney Injury
Kidney Diseases
Renal Insufficiency
Urologic Diseases

ClinicalTrials.gov processed this record on October 29, 2014