A Study in Sepsis Patients With Renal Failure

March 30, 2012 updated by: AM-Pharma

A Phase-IIa, Double-blind, Randomized, Placebo-controlled Study on the Safety and Early Efficacy of Alkaline Phosphatase in Sepsis Patients With Renal Failure

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium
        • University Medical Center Antwerp (UZA)
      • Brussels, Belgium
        • ULB Hôpital Erasme
      • Brussels, Belgium
        • Universitair Ziekenhuis Brussel
      • Brussels, Belgium
        • Cliniques Universitaires Saint Luc-UCL
  • Netherlands
      • 's-Hertogenbosch, Netherlands
        • Jeroen Bosch Ziekenhuis lokatie GZG
      • Amsterdam, Netherlands
        • VU University Medical Center
      • Nijmegen, Netherlands
        • Canisius Wilhelmina Ziekenhuis
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500 HB
        • UMC Nijmegen University Medical Center St Radboud
    • Overijssel
      • Zwolle, Overijssel, Netherlands, 8011 JW
        • Isala Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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".

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Haematology, biochemistry, and microbiological evaluation. Adverse event monitoring.
Time Frame: 28 Days
28 Days

Secondary Outcome Measures

Outcome Measure
Time Frame
To investigate the effect of AP on inflammatory parameters in sepsis patients with renal failure.
Time Frame: 28 Days
28 Days
To investigate the effect of AP on clinical variables in sepsis patients with renal failure.
Time Frame: 28 Days
28 Days
To investigate the effect of AP on renal function markers in sepsis patients with renal failure.
Time Frame: 28 Days
28 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AM-Pharma

Investigators

  • Principal Investigator: Professor J G van der Hoeven, MD, PhD, University Medical Center St Radboud, Nijmegen, The Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (ACTUAL)

December 1, 2009

Study Completion (ACTUAL)

December 1, 2009

Study Registration Dates

First Submitted

August 2, 2007

First Submitted That Met QC Criteria

August 2, 2007

First Posted (ESTIMATE)

August 3, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

April 2, 2012

Last Update Submitted That Met QC Criteria

March 30, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AP REN 01-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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