Bicarbonate in Cardiac Surgery

NCT00878956 | Terminated Phase 2 DMC

• 1 other identifier: H2007/02808
• Study Type: interventional
• Target: 427
• Locations: 2 countries
• Sites: 4

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.

Conditions

Acute Kidney Injury

Keywords

Cardiac surgery; Cardiopulmonary bypass; Oxidative stress; Acute renal dysfunction; Sodium bicarbonate

Outcome Measures

Primary Outcomes (1)

• 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

  within first five postoperative days

Secondary Outcomes (10)

• Mean changes in serum creatinine after adjustment for relevant baseline variables

  within first five postoperative days

• mean changes in serum cystatin C after adjustment for relevant baseline variables

  within first five postoperative days

• mean changes in urinary neutrophil gelatinase-associated lipocalin (NGAL)after adjustment for relevant baseline variables

  within first five postoperative days

• Duration of ventilation

  Until time of extubation from mechanical ventilation

• Proportion of patients developing any of the RIFLE criteria: R, I or F

  within first five postoperative days

Study Arms (2)

1

ACTIVE COMPARATOR

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

2

PLACEBO COMPARATOR

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

Interventions

Sodium Bicarbonate DRUG

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).

1

Sodium Chloride DRUG

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).

2

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Austin Health: lead

Study Sites (4)

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

Warringal Private Hospital

Melbourne, Victoria, 3084, Australia

Location

Auckland City Hospital

Auckland, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Sodium Bicarbonate; Sodium Chloride

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds

Study Officials

• Rinaldo Bellomo, MD, FRACP

  Austin Hospital, Melbourne Australia

  PRINCIPAL INVESTIGATOR

• Frank van Haren, MD

  Waikato Hospital, Hamilton, New Zealand

  STUDY CHAIR

• Shay McGuinness, MB ChB, FRCA, FANZCA

  Auckland City Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of ICU Research

Study Record Dates

• First Submitted: April 8, 2009
• First Posted: April 9, 2009
• Study Start: April 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: January 1, 2012
• Last Updated: August 1, 2012

Record last verified: 2012-07

Locations

AU (2); NZ (2)