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

Study Overview
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Brief Summary
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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).

Detailed Description
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The investigators hypothesise: 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. 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. 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.

Official Title
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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

Conditions
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Systemic Inflammatory Response Syndrome, Oliguria, Renal Impairment

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Drug: Sodium chloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sodium bicarbonate, serum neutrophil gelatinase associated lipocalin, renal impairment, renal failure, systemic inflammatory response syndrome, defined, by serum NGAL ≥ 100 ng/ml.