Bicarbonate and Lipocalin in Systemic Inflammatory Response Syndrome (SIRS) Study - Full Text View

Purpose

We will determine the efficacy of intravenous sodium bicarbonate in reducing progression to overt acute renal failure in patients with low urine output, the systemic inflammatory response syndrome, and early acute renal impairment as defined by a new and experimental test of renal function, serum neutrophil gelatinase-associated lipocalin (NGAL).

Condition	Intervention	Phase
Systemic Inflammatory Response Syndrome Oliguria Renal Impairment	Drug: Sodium bicarbonate Drug: Placebo	Phase II

MedlinePlus related topics:

Urine and Urination

Drug Information available for:

Sodium chloride Chlorides Sodium bicarbonate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	A Randomized Double-Blind Placebo-Controlled Pilot Trial of NGAL-Directed Sodium Bicarbonate to Protect Renal Function in Patients With the Systemic Inflammatory Response Syndrome and Oliguria

Further study details as provided by Austin Health:

Primary Outcome Measures:

The development of renal impairment of at least RIFLE class 'I'. (Crit Care 2004 8(4): R204-12) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Institution of renal replacement therapy [ Designated as safety issue: No ]
Duration of ICU stay [ Designated as safety issue: No ]
Duration of hospital stay [ Designated as safety issue: No ]
Hospital mortality [ Designated as safety issue: No ]
Hospital discharge with the ongoing requirement for renal replacement therapy [ Designated as safety issue: No ]
Peak serum NGAL and cystatin C. [ Designated as safety issue: No ]
Peak urine NGAL, IL-18 and cystatin C [ Designated as safety issue: No ]

Estimated Enrollment:	170
Study Start Date:	August 2008

Arms	Assigned Interventions
Sodium bicarbonate: Active Comparator	Drug: Sodium bicarbonate Sodium bicarbonate: loading dose of 0.5 mmol/Kg and then continuous infusion of 0.2 mmol/Kg/hr
Placebo: Placebo Comparator	Drug: Placebo 0.9% sodium chloride

Detailed Description:

We hypothesise:

In patients with SIRS (including the subsets of patients with greater illness severity, such as severe sepsis and septic shock), sodium bicarbonate will delay or avert the development of acute renal failure (RIFLE class I, F, L or E).
In patients with SIRS (including the subsets of patients with greater illness severity, such as severe sepsis and septic shock), serum NGAL is a sensitive and specific predictor of the subsequent development of acute renal failure (RIFLE class I, F, L or E).
Serum NGAL can accurately identify patients with SIRS who will gain the greatest benefit from an intervention capable of delaying or averting the progression of early renal impairment to acute renal failure.
Changes in serum NGAL with and without treatment with sodium bicarbonate are more predictive of subsequent clinical course at an earlier time point than are conventionally measured markers of renal function (serum creatinine, serum urea, calculated glomerular filtration rate) and other experimental markers of renal function (urine IL-18 and NGAL, serum or urine cystatin C).

To test these hypotheses we have designed a protocol that simultaneously tests both NGAL as a diagnostic strategy and sodium bicarbonate as a therapeutic intervention.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706771

Contacts


Contact: Michael C Reade, MBBS DPhil	39-496-5000 ext 4838	michael.reade@austin.org.au

Contact: Forbes McGain, MBBS FJFICM	38-345-6666	Forbes.McGain@wh.org.au

Locations


Australia, Victoria
	Northern Hospital
	Epping, Victoria, Australia, 3076
	Austin Hospital
	Heidelberg, Melbourne, Victoria, Australia, 3084
	Western Hospital
	Footscray, Victoria, Australia

Sponsors and Collaborators

Austin Health

Investigators


Principal Investigator:	Michael C Reade, MBBS DPhil	Austin & Northern Hospitals, University of Melbourne

Principal Investigator:	Forbes McGain, MBBS FJFICM	Western Hospital, University of Melbourne

Principal Investigator:	Rinaldo Bellomo, MD FJFICM	Austin Hospital, University of Melbourne

More Information

Responsible Party:	The Northern Hospital, Melbourne, Australia ( Associate Professor Michael C. Reade )
Study ID Numbers:	TNH 18/08
First Received:	June 26, 2008
Last Updated:	June 27, 2008
ClinicalTrials.gov Identifier:	NCT00706771
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:

sodium bicarbonate

serum neutrophil gelatinase associated lipocalin

renal impairment

renal failure

systemic inflammatory response syndrome

defined

by serum NGAL ≥ 100 ng/ml.

Study placed in the following topic categories:

Systemic Inflammatory Response Syndrome

Signs and Symptoms

Shock

Urologic Diseases

Urination Disorders

Oliguria

Inflammation

Kidney Failure

Additional relevant MeSH terms:

Urological Manifestations

Pathologic Processes

Disease

Syndrome

ClinicalTrials.gov processed this record on December 03, 2008

Sponsored by:	Austin Health
Information provided by:	Austin Health
ClinicalTrials.gov Identifier:	NCT00706771