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A Study in Sepsis Patients With Renal Failure

This study has been terminated.
(sufficient POC to switch development from bovine AP to recombinant AP)
Sponsor:
Information provided by (Responsible Party):
AM-Pharma
ClinicalTrials.gov Identifier:
NCT00511186
First received: August 2, 2007
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

The purpose of this study is to investigate the safety and tolerability of AP in sepsis patients with renal failure and to investigate the effect of AP on inflammatory and clinical parameters in sepsis patients with renal failure.


Condition Intervention Phase
Sepsis
Bacterial Infections and Mycoses
Drug: Placebo
Drug: BIAP
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase-IIa, Double-blind, Randomized, Placebo-controlled Study on the Safety and Early Efficacy of Alkaline Phosphatase in Sepsis Patients With Renal Failure

Resource links provided by NLM:


Further study details as provided by AM-Pharma:

Primary Outcome Measures:
  • Haematology, biochemistry, and microbiological evaluation. Adverse event monitoring. [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To investigate the effect of AP on inflammatory parameters in sepsis patients with renal failure. [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
  • To investigate the effect of AP on clinical variables in sepsis patients with renal failure. [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
  • To investigate the effect of AP on renal function markers in sepsis patients with renal failure. [ Time Frame: 28 Days ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: May 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bovine Intestinal AP
Bovine Intestinal Alkaline Phosphatase (BIAP) Intravenous administration of 10" bolus (67,5U/kg) and 48h continuous infusion (132,5U/kg)
Drug: BIAP
AP is administered intravenously over 48 hours. An initial loading dose of 67.5U/Kg body weight over 10-minutes is followed by continuous infusion of 132.5U/Kg/24H administered over 48H
Other Names:
  • BIAP
  • AP
Placebo Comparator: 2
Placebo Intravenous administration of 10" bolus and 48h continuous infusion
Drug: Placebo
placebo is administered intravenously over 48 hours. An initial loading dose of over 10-minutes is followed by continuous infusion over 48h.
Other Name: Placebo

Detailed Description:

RATIONALE FOR THE STUDY

A previous clinical study conducted in centers in The Netherlands and Belgium have shown a substantial clinical benefit of AP treatment in patients with sepsis and associated acute renal failure (see Introduction above). The latter results require confirmation in a prospective study, as the current subject of this Protocol.

Choice of Drugs

The proposed study medication (AP) is identical to the study medication used in the previous clinical study in sepsis patients with single or multiple end-organ failure. Since there is no current proven treatment for these patients, the controls (as in previous studies) is placebo.

Choice of patient population

The aim is to enroll a maximum of 26 patients positive for sepsis with an APACHE score of ≥20 and ≤28 (determined within 24 hours of entry), and who will be analyzed on an intention to treat (ITT) basis.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients between the age of 18 and 80 years.
  • Proven or suspected infection.
  • Two out of four SIRS criteria of systemic inflammation, existing for less than 24 hours after admission in the intensive care unit, as follows:

    • Core temperature higher then 38 degree Celsius or lower then 36 degree Celsius.
    • Heart rate above 90 beats/min (unless the patient has a medical condition known to increase heart rate or is receiving treatment that would prevent tachycardia).
    • Respiratory rate above 20 breaths/min, a PaCO2 lower then 32mmHg or the use of mechanical ventilation for an acute respiratory process.
    • White-cell count above 12,000/mm3 or below 4,000/mm3 or a differential count showing >10 percent immature neutrophils.
  • Acute renal failure, defined as

    • Rise in serum creatinine level to ≥150μmol/L within the previous 48 hours, in the absence of primary underlying renal disease OR
    • Minimally a stage 1 Kidney Injury according to AKIN creatinine criteria: Increase in serum creatinine ≥26.2µmol/L (0.3mg/dL) or increase to ≥150% (≥1.5 -fold) from baseline in the previous 48 hours in the absence of primary underlying renal disease and where baseline creatinine is less than 150 µmol/L) OR
    • Minimally a stage 1 Kidney Injury according to AKIN Urine Output criteria: Urine Output of ≤ 0.5mg/kg/h for ≥6h and following adequate fluid resuscitation when applicable, in the absence of underlying primary renal disease and where baseline creatinine is less than 150µmol/L)
  • Written informed consent obtained prior to any study intervention.

Exclusion Criteria:

  • Pregnant women or nursing mothers and fecund females who are not on effective contraception (chemical: pill; or mechanical: IUD)
  • Patients already on dialysis (RTT) at entry
  • Known HIV (sero-positive) patients
  • Patients receiving immunosuppressant therapy or on chronic high doses of steroids equivalent to prednisone 1mg/Kg/day
  • Patients expected to have rapidly fatal disease within 24 hours
  • Known confirmed gram-positive sepsis
  • Known confirmed fungal sepsis
  • 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
  • Any previous administration of active study medication.
  • Known allergy for dairy (bovine) products including cow milk.
  • Sepsis without renal failure as defined in the Entry Criteria.
  • History of chronic renal failure or history of persistent creatinine level equal or greater than 150umol/L prior to entry for reasons other than the current sepsis condition".
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511186

Locations
Belgium
University Medical Center Antwerp (UZA)
Antwerp, Belgium
ULB Hopital Erasme
Brussels, Belgium
Universitair Ziekenhuis Brussel
Brussels, Belgium
Cliniques Universitaires Saint Luc-UCL
Brussels, Belgium
Netherlands
UMC Nijmegen University Medical Center St Radboud
Nijmegen, Gelderland, Netherlands, 6500 HB
Isala Clinics
Zwolle, Overijssel, Netherlands, 8011 JW
Jeroen Bosch Ziekenhuis lokatie GZG
's-Hertogenbosch, Netherlands
VU University Medical Center
Amsterdam, Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Sponsors and Collaborators
AM-Pharma
Investigators
Principal Investigator: Professor J G van der Hoeven, MD, PhD University Medical Center St Radboud, Nijmegen, The Netherlands
  More Information

Additional Information:
Publications:
Responsible Party: AM-Pharma
ClinicalTrials.gov Identifier: NCT00511186     History of Changes
Other Study ID Numbers: AP REN 01-01
Study First Received: August 2, 2007
Last Updated: March 30, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by AM-Pharma:
Sepsis
Alkaline Phosphatase
inflammation
infection
renal failure

Additional relevant MeSH terms:
Bacterial Infections
Infection
Renal Insufficiency
Sepsis
Toxemia
Inflammation
Kidney Diseases
Pathologic Processes
Systemic Inflammatory Response Syndrome
Urologic Diseases

ClinicalTrials.gov processed this record on November 25, 2014