NCT00430859

Brief Summary

Eligible patients will receive either AP or matching placebo in a double blind, randomized design and following a 2:1 ratio. All medication will be given in addition to standard care for sepsis patients. Patients will be followed for 28 days after the start of study medication administration. A blinded safety review of the study results will take place after the inclusion of 12 patients in the study.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at below P25 for phase_2 sepsis

Timeline
Completed

Started Sep 2004

Geographic Reach
2 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2004

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2006

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2006

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

February 1, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 2, 2007

Completed
Last Updated

April 2, 2012

Status Verified

March 1, 2012

Enrollment Period

1.5 years

First QC Date

February 1, 2007

Last Update Submit

March 30, 2012

Conditions

SepsisMultiple Organ Dysfunction Syndrome

Keywords

SepsisAlkalinePhosphataseLipopolysaccharide

Outcome Measures

Primary Outcomes (1)

  • Presence of (Serious) Adverse Events ((S)AEs), vital signs (body temperature, heart rate), systolic and diastolic blood pressure, electrocardiogram variables, biochemical, haematological, and coagulation variables, and frequency and type of anti-AP.

    28 days

Secondary Outcomes (3)

  • Variables for evaluation of the effect on inflammation: C-reactive protein (CRP), plasma lactate, cytokines (TNFalfa, IL-6, IL-8, IL-10), white cell count, and procalcitonin (PCT) were assessed.differential

    28

  • Evaluation effect: APACHE-II score, overall mortality at 28 days, length of stay at ICU, number of days requiring mechanical ventilation, length of stay in hospital, SOFA score, and number of dysfunctional organs were assessed.

    28

  • Clinical assessment after 90 days

    90 days

Study Arms (2)

1

EXPERIMENTAL

BIAP

Drug: Alkaline Phosphatase

Placebo

PLACEBO COMPARATOR

Placebo, saline

Drug: Placebo

Interventions

Alkaline PhosphataseDRUG

Intravenous over a period of 24 hours

Also known as: AP, BIAP, CIAP
1
PlaceboDRUG

Saline over a period of 24h

Also known as: saline
Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients between 18 and 80 years (inclusive);
  • proven or suspected infection;
  • meeting 2 of 4 of the systemic inflammatory response syndrome (SIRS) criteria;
  • septic shock or one or more acute organ failures in the preceding 12 hours;
  • written informed consent obtained.

You may not qualify if:

  • Pregnant or lactating women;
  • known HIV seropositive patients;
  • patients receiving immunosuppressive therapy or chronically using high doses of glucocorticosteroids (defined as \> 1 mg/kg/day) equivalent to prednisone 1 mg/kg/day;
  • patients expected to have rapidly fatal disease within 24 h;
  • known confirmed gram-positive sepsis;
  • known confirmed fungal sepsis;
  • chronic renal failure requiring haemodialysis or peritoneal dialysis;
  • acute pancreatitis with no established source of infection;
  • patients not expected to survive for 28 days due to other medical conditions such as end-stage neoplasm or other diseases;
  • participation in another investigational study within 90 days prior to start of the study which might interfere with this study;
  • previous administration of AP;
  • known allergy for cow milk.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Hospital Network Antwerpen - Middelheim

Antwerp, Antwerpen, B-2020, Belgium

Location

University Hospital Antwerpen

Antwerp, Antwerpen, B-2650, Belgium

Location

University Hospital Vrije Universiteit Brussel

Brussels, Brussels Capital, B-1090, Belgium

Location

University Medical Centre St. Radboud

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

St. Elisabeth Hospital

Tilburg, North Brabant, 5022 GC, Netherlands

Location

Isala Clinics

Zwolle, Overijssel, 8011 JW, Netherlands

Location

Medical Centre Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

University Medical Centre Groningen

Groningen, Provincie Groningen, 9700 RB, Netherlands

Location

University Medical Centre Utrecht

Utrecht, Utrecht, 3508 GA, Netherlands

Location

Erasmus Medical Centre

Rotterdam, Z-Holland, 3015 GD, Netherlands

Location

Related Publications (10)

  • Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. doi: 10.1056/NEJMoa022139.

    PMID: 12700374BACKGROUND

  • Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA. 1995 Jan 11;273(2):117-23.

    PMID: 7799491BACKGROUND

  • From the Centers for Disease Control. Increase in National Hospital Discharge Survey rates for septicemia--United States, 1979-1987. JAMA. 1990 Feb 16;263(7):937-8. No abstract available.

    PMID: 2299753BACKGROUND

  • Angus DC, Birmingham MC, Balk RA, Scannon PJ, Collins D, Kruse JA, Graham DR, Dedhia HV, Homann S, MacIntyre N. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators. JAMA. 2000 Apr 5;283(13):1723-30. doi: 10.1001/jama.283.13.1723.

    PMID: 10755499BACKGROUND

  • Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA. 2000 Feb 23;283(8):1038-45. doi: 10.1001/jama.283.8.1038.

    PMID: 10697064BACKGROUND

  • Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, Ognibene FP. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med. 1990 Aug 1;113(3):227-42. doi: 10.7326/0003-4819-113-3-227.

    PMID: 2197912BACKGROUND

  • Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. 1997 Jul;112(1):235-43. doi: 10.1378/chest.112.1.235. No abstract available.

    PMID: 9228382BACKGROUND

  • Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.

    PMID: 1303622BACKGROUND

  • Heemskerk S, Masereeuw R, Moesker O, Bouw MP, van der Hoeven JG, Peters WH, Russel FG, Pickkers P; APSEP Study Group. Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients. Crit Care Med. 2009 Feb;37(2):417-23, e1. doi: 10.1097/CCM.0b013e31819598af.

    PMID: 19114895RESULT

  • Pickkers P, Snellen F, Rogiers P, Bakker J, Jorens P, Meulenbelt J, Spapen H, Tulleken JE, Lins R, Ramael S, Bulitta M, van der Hoeven JG. Clinical pharmacology of exogenously administered alkaline phosphatase. Eur J Clin Pharmacol. 2009 Apr;65(4):393-402. doi: 10.1007/s00228-008-0591-6. Epub 2008 Dec 2.

    PMID: 19048243RESULT

MeSH Terms

Conditions

SepsisMultiple Organ Failure

Interventions

Alkaline Phosphatase2-(3',4'-dihydroxyphenyl-1-azo)benzimidazoleSodium Chloride

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

Phosphoric Monoester HydrolasesEsterasesHydrolasesEnzymesEnzymes and CoenzymesChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Bart Wuurman, M.Sc.

    STUDY CHAIR

  • Hans JG van der Hoeven, MD, PhD

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2007

First Posted

February 2, 2007

Study Start

September 1, 2004

Primary Completion

March 1, 2006

Study Completion

March 1, 2006

Last Updated

April 2, 2012

Record last verified: 2012-03

Locations

NL(7)BE(3)