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

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

Purpose

The investigators 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

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 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

Resource links provided by NLM:

MedlinePlus related topics: Urine and Urination

Drug Information available for: Sodium bicarbonate

U.S. FDA Resources

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) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Institution of renal replacement therapy [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Duration of ICU stay [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Duration of hospital stay [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Hospital mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Hospital discharge with the ongoing requirement for renal replacement therapy [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Peak serum NGAL and cystatin C. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Peak urine NGAL, IL-18 and cystatin C [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	170
Study Start Date:	February 2010
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

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

Detailed Description:

The investigators 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 the investigators 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	Not yet recruiting
Epping, Victoria, Australia, 3076
Contact: Michael C Reade, MBBS DPhil 39-496-5000 ext 4838 michael.reade@austin.org.au
Contact: Graeme Duke, MD FJFICM 38-405-8000 graeme.duke@nh.org.au
Principal Investigator: Michael C Reade, MBBS DPhil
Sub-Investigator: Graeme Duke, MD FJFICM
Sub-Investigator: Mary Park, RN
Western Hospital	Not yet recruiting
Footscray, Victoria, Australia
Contact: Forbes McGain, MBBS FJFICM 38-345-6666 forbes.mcgain@wh.org.au
Principal Investigator: Forbes McGain, MBBS FJFICM
Sub-Investigator: Craig French, MBBS FJFICM
Sub-Investigator: Heike Raunow, RN
Austin Hospital	Not yet recruiting
Heidelberg, Melbourne, Victoria, Australia, 3084
Contact: Michael C Reade, MBBS DPhil 39-496-5000 ext 4838 michael.reade@austin.org.au
Contact: Rinaldo Bellomo, MD FJFICM 39-496-5000 rinaldo.bellomo@austin.org.au
Principal Investigator: Rinaldo Bellomo, MD FJFICM
Sub-Investigator: Michael C Reade, MBBS DPhil
Sub-Investigator: Donna Goldsmith, RN

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

No publications provided

Responsible Party:	Associate Professor Michael C. Reade, The Northern Hospital, Melbourne, Australia
ClinicalTrials.gov Identifier:	NCT00706771 History of Changes
Other Study ID Numbers:	TNH 18/08
Study First Received:	June 26, 2008
Last Updated:	June 22, 2011
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.

Additional relevant MeSH terms:

Oliguria
Systemic Inflammatory Response Syndrome
Renal Insufficiency
Urination Disorders
Urologic Diseases
Urological Manifestations

Signs and Symptoms
Inflammation
Pathologic Processes
Shock
Kidney Diseases

ClinicalTrials.gov processed this record on February 12, 2012