A Study in Sepsis Patients With Renal Failure

NCT00511186 | Terminated Phase 2 DMC

• 1 other identifier: AP REN 01-01
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 9

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.

Conditions

Sepsis; Bacterial Infections and Mycoses

Keywords

Sepsis; Alkaline Phosphatase; inflammation; infection; renal failure

Outcome Measures

Primary Outcomes (1)

• Haematology, biochemistry, and microbiological evaluation. Adverse event monitoring.

  28 Days

Secondary Outcomes (3)

• 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

Study Arms (2)

Bovine Intestinal AP

EXPERIMENTAL

Bovine Intestinal Alkaline Phosphatase (BIAP) Intravenous administration of 10" bolus (67,5U/kg) and 48h continuous infusion (132,5U/kg)

Drug: BIAP

2

PLACEBO COMPARATOR

Placebo Intravenous administration of 10" bolus and 48h continuous infusion

Drug: Placebo

Interventions

Placebo DRUG

placebo is administered intravenously over 48 hours. An initial loading dose of over 10-minutes is followed by continuous infusion over 48h.

2

BIAP DRUG

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

Also known as: AP

Bovine Intestinal AP

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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".

Sponsors & Collaborators

• AM-Pharma: lead

Study Sites (9)

University Medical Center Antwerp (UZA)

Antwerp, Belgium

Location

Cliniques Universitaires Saint Luc-UCL

Brussels, Belgium

Location

ULB Hopital Erasme

Brussels, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, Belgium

Location

UMC Nijmegen University Medical Center St Radboud

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Isala Clinics

Zwolle, Overijssel, 8011 JW, Netherlands

Location

Jeroen Bosch Ziekenhuis lokatie GZG

's-Hertogenbosch, Netherlands

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

Location

Related Publications (1)

• Pickkers P, Heemskerk S, Schouten J, Laterre PF, Vincent JL, Beishuizen A, Jorens PG, Spapen H, Bulitta M, Peters WH, van der Hoeven JG. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care. 2012 Jan 23;16(1):R14. doi: 10.1186/cc11159.

  PMID: 22269279 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Sepsis; Bacterial Infections and Mycoses; Inflammation; Infections; Renal Insufficiency

Interventions

2-(3',4'-dihydroxyphenyl-1-azo)benzimidazole

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Professor J G van der Hoeven, MD, PhD

  University Medical Center St Radboud, Nijmegen, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2007
• First Posted: August 3, 2007
• Study Start: May 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: April 2, 2012

Record last verified: 2012-03

Locations

BE (4); NL (5)