Effects of Alkaline Phosphatase on Renal Function in Septic Patients

NCT00457613 | Completed Phase 2

• 1 other identifier: PP05
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Septic shock is the most common cause of death in patients requiring intensive care. The kidney is one of the first organs to fail, stressing the importance to search for clinical interventions that may protect the kidneys during sepsis. Alkaline phosphatase functions as a host defence molecule and is present in many cells and organs (e.g. intestine, placenta, liver, kidney and bone). Alkaline phosphatase has a dual mode of action. First, it binds to and, subsequently, dephosphorylates lipopolysaccharide (LPS). Second, the enzymatic reaction product monophosphoryl-LPS is a non-toxic substance for mammals which acts as a partial antagonist on the LPS receptor complex. In several animal studies, administration of alkaline phosphatase attenuates the inflammatory response and reduces mortality. It is unknown whether these results can be extrapolated to septic patients . We studied the effects of alkaline phosphatse administration on kidney damage and function in patients with severe sepsis or septic shock.

Conditions

Severe; Septic; Shock

Keywords

alkaline phosphatase; sepsis; kidney function

Outcome Measures

Primary Outcomes (3)

• Biomarkers of kidney damage

• kidney function

• markers of inflammation

Interventions

bolus injection, followed by a continuous infusion ( 24 h) (Alkaline phosphatase) DRUG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Proven or suspected Gram-negative bacterial infection
• Two out of four Systemic Inflammatory Response Syndrome (SIRS) criteria existing for less than 24 h
• Acute onset of end-organ dysfunction in the preceding 12 h

You may not qualify if:

• Prior therapy with alkaline phosphatase
• Known allergy for cow milk
• Probable death within 24 h
• Chronic renal failure requiring hemodialysis or peritoneal dialysis
• Acute pancreatitis with no established source of infection
• HIV seropositive
• Pregnant or lactating
• Confirmed Gram-positive or fungal sepsis
• Treatment with immunosuppressants including high doses of glucocorticosteroids

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Shock; Sepsis

Interventions

Alkaline Phosphatase

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Phosphoric Monoester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 4, 2007
• First Posted: April 6, 2007
• Study Start: November 1, 2004
• Study Completion: March 1, 2006
• Last Updated: April 6, 2007

Record last verified: 2006-03

Locations

NL (1)