Bicarbonate and Lipocalin in Systemic Inflammatory Response Syndrome (SIRS) Study (BLISS)

A Randomized Double-blind Controlled Pilot Feasibility and Safety Trial of NGAL-directed Sodium Bicarbonate to Protect Renal Function in Patients With the Systemic Inflammatory Response Syndrome, Oliguria and Elevated Lipocalin Levels

The investigators will determine the feasibility, safety and efficacy of intravenous sodium bicarbonate in reducing progression to overt acute renal failure in patients with the systemic inflammatory response syndrome, and low urine output or early acute renal impairment as defined by serum neutrophil gelatinase-associated lipocalin (NGAL).

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome; Renal Impairment; Oliguria
• Intervention / Treatment: Drug: Sodium bicarbonate; Drug: Sodium chloride

Detailed Description

The investigators hypothesise:

1. In patients with SIRS and oliguria the early administration of sodium bicarbonate or sodium chloride (control) triggered by an abnormally high NGAL level is feasible.
2. In patients with SIRS and oliguria the early administration of sodium bicarbonate or sodium chloride (control) triggered by an abnormally high NGAL level is safe.
3. In patients with SIRS and oliguria the early administration of sodium bicarbonate or sodium chloride (control) triggered by an abnormally high NGAL level leads to signs or trends of efficacy as measured by serum creatinine derived indices.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Melbourne, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3154
      • Royal Melbourne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consent obtained
• Diagnosis of SIRS. Requires any TWO of:

temperature > 38°C or < 36°C OR heart rate > 90 beats/min OR respiratory rate > 20 breaths/min. PaCO2 < 32 mm Hg OR alteration of white blood cell count > 12,000 cells/mm3, < 4,000 cells/mm3, or the presence of > 10% immature neutrophils

• elevated lipocalin level
• Arterial line already in place
• Central venous catheter already in place
• Age ≥ 18 years
• Within 24 hours of admission to the ICU

Exclusion Criteria:

• Unlikely to remain in ICU for >72 hours
• Moribund patient
• Pre-existing CKD, transplant or ESRD
• Receiving (or about to receive) continuous renal replacement therapy for acute renal failure at time of enrolment
• Diagnosis of acute GN, AIN, vasculitis or post-renal aetiology
• Known/suspected study allergy to sodium bicarbonate
• Enrolling physician concern about patient enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium bicarbonate; sodium bicarbonate: loading of 0.5 mmol/kg and the continuous infusion o f0.2 mmol/kg/hr	Drug: Sodium bicarbonate; Sodium bicarbonate: loading dose of 0.5 mmol/Kg and then continuous infusion of 0.2 mmol/Kg/hr
Active Comparator: Sodium chloride; sodium chloride: loading of 0.5 mmol/kg and the continuous infusion o f0.2 mmol/kg/hr	Drug: Sodium chloride; 0.9% sodium chloride: loading dose of 0.5 mmol/Kg and then continuous infusion of 0.2 mmol/Kg/hr

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The ability to deliver the study protocol safely and rapidly with a trend to improved renal outcomes	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Attenuation in lipocalin levels	28 days
Decrease in the magnitude in serum creatinine rise	28 days
Ability to deliver the study protocol without significant biochemical side effects	28 days

Collaborators and Investigators

• Sponsor: Austin Health
• Investigators: Principal Investigator: Michael C Reade, MBBS DPhil, Austin & Northern Hospitals, University of Melbourne; Principal Investigator: Nerina Harley, MBBS FCICM, Melbourne Health; Principal Investigator: Rinaldo Bellomo, MD FJFICM, Austin Hospital, University of Melbourne

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 26, 2008
• First Submitted That Met QC Criteria: June 27, 2008
• First Posted (Estimate): June 30, 2008

Study Record Updates

• Last Update Posted (Estimate): June 30, 2014
• Last Update Submitted That Met QC Criteria: June 26, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: sodium bicarbonate; serum neutrophil gelatinase associated lipocalin; renal impairment; renal failure; systemic inflammatory response syndrome; defined; by serum NGAL ≥ 100 ng/ml.
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Inflammation; Urological Manifestations; Disease; Urination Disorders; Shock; Syndrome; Renal Insufficiency; Systemic Inflammatory Response Syndrome; Oliguria
• Other Study ID Numbers: TNH 18/08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No