A Study in Sepsis Patients With Renal Failure

Sponsor

AM-Pharma (Industry)

Overall Status

Terminated

CT.gov ID

NCT00511186

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Sepsis Bacterial Infections and Mycoses	Drug: Placebo Drug: BIAP	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

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.

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:

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.

Outcome Measures

Primary Outcome Measures

Haematology, biochemistry, and microbiological evaluation. Adverse event monitoring. [28 Days]

Secondary Outcome Measures

To investigate the effect of AP on inflammatory parameters in sepsis patients with renal failure. [28 Days]
To investigate the effect of AP on clinical variables in sepsis patients with renal failure. [28 Days]
To investigate the effect of AP on renal function markers in sepsis patients with renal failure. [28 Days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University Medical Center Antwerp (UZA)	Antwerp		Belgium
2	Cliniques Universitaires Saint Luc-UCL	Brussels		Belgium
3	ULB Hopital Erasme	Brussels		Belgium
4	Universitair Ziekenhuis Brussel	Brussels		Belgium
5	UMC Nijmegen University Medical Center St Radboud	Nijmegen	Gelderland	Netherlands	6500 HB
6	Isala Clinics	Zwolle	Overijssel	Netherlands	8011 JW
7	Jeroen Bosch Ziekenhuis lokatie GZG	's-Hertogenbosch		Netherlands
8	VU University Medical Center	Amsterdam		Netherlands
9	Canisius Wilhelmina Ziekenhuis	Nijmegen		Netherlands