Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR;137; CIAP 02-01
Study information
Scientific title
Acronym
APSEP study
Study hypothesis
Unlike other potential sepsis treatments, alkaline phosphatase has been shown to act at the front end of the inflammatory cascade. By doing so, it eliminates the root cause of the Systemic Inflammatory Response Syndrome (SIRS), and prevents the progression into sepsis and septic shock.
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Multicentre, randomised, double blind, placebo controlled, parallel group
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Sepsis
Intervention
Patients will be assigned to receive either CIAP or placebo administered intravenously over 24 hours.
Patients randomised to CIAP will receive an initial bolus injection of 67.5 U/kg body weight administered over 10 minutes, followed by continuous infusion of 132.5 U/kg, administered over the remaining 23 hours and 50 minutes.
Patients randomised to placebo will receive the same quantities of corresponding injection fluids, without the active compound.
Intervention type
Drug
Phase
Not Specified
Drug names
Calf Intestinal Alkaline Phosphatase (CIAP)
Primary outcome measure
Safety:
1. (Serious) adverse events
2. Antibodies against CIAP
3. Electrocardiogram (ECG) parameters
4. Biochemical safety parameters
5. Haematological parameters
6. Coagulation parameters
Efficacy (primary effect parameters):
1. C-Reactive Protein (CRP)
2. Plasma lactate
3. Cytokines (Tumour Necrotising Factor alpha [TNF-α], Interleukin-1 [IL-1], Interleukin-4 [IL-4], Interleukin-6 [IL-6], Interleukin-8 [IL-8] and Interleukin-10 [IL-10])
4. White cell differential cell count
5. Procalcitonin
6. Lipopolysaccharide (LPS)
Secondary outcome measures
Efficacy (secondary effect parameters):
1. Body temperature
2. Heart rate
3. Blood pressure
4. Acute Physiology And Chronic Health Evaluation (APACHE-II) score
5. Overall mortality at 28 days
6. Length of stay at Intensive Care Unit (ICU)
7. Number of days requiring mechanical ventilation
8. Length of stay in hospital
9. Sequential Organ Failure Assessment (SOFA)
10. Number of dysfunctional organs
Overall trial start date
01/08/2004
Overall trial end date
01/03/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients greater than or equal to 18 years and less than or equal to 80 years
2. Proven or suspected infection
3. Two out of four SIRS criteria of systemic inflammation, existing for less than 24 hours after admission in the intensive care unit:
a. core temperature greater than or equal to 38 or less than or equal to 36°Celsius
b. heart rate greater than of equal to 90 beats/min (unless the patient has a medical condition known to increase heart rate or is receiving treatment that would prevent tachycardia)
c. respiratory rate greater than or equal to 20 breaths/min, an arterial carbon dioxide pressure (PaCO2) less than or equal to 32 mmHg or the use of mechanical ventilation for an acute respiratory process
d. white-cell count greater than or equal to 12,000/mm^3 or less than or equal to 4,000/mm^3 or a differential count showing more than 10% immature neutrophils
4. Acute onset of end-organ dysfunction in the preceding 12 hours unrelated to the primary septic focus and not explained by any underlying chronic disease as indicated by one or more of the following:
a. sustained hypotension or organ dysfunction that is the result of sepsis and not the patients underlying disease or treatment, as evidenced by one or more of the following criteria for less than 12 hours:
i. systolic blood pressure less than or equal to 90 mmHg or mean arterial pressure less than or equal to 70 mmHg for at least one hour (by two or more measurements) despite adequate fluid intake, or
ii. a requirement for vasopressor support to maintain Mean Arterial Pressure (MAP)
b. acute renal failure, defined by either oliguria (a urine output less than or equal to 0.5 ml/kg/hour for at least two consecutive hours or a rise in serum creatinine concentration greater than or equal to 177 µmol/l (2.0 mg/dl) within the previous 48 hours, in the absence of primary underlying renal disease
c. acute alteration in mental state not due to sedation or of primary underlying disease of the central nervous system
d. acute hypoxemic respiratory failure, defined by a Partial Pressure of Oxygen in Arterial Blood (PaO2)/Fraction of Inspired Oxygen (FiO2) ratio less than 40 kPa (300 mmHg) in the absence of primary underlying pulmonary disease
e. disseminated intravascular coagulopathy defined by either:
i. platelet count less than or equal to 100 x 10^9/l
ii. coagulation abnormality (Prothrombin Time [PT] 1.2 times control or Activated Partial Thromboplastin Time [APTT] 1.2 times control)
f. metabolic acidosis defined as pH less than or equal to 7.30 or base excess less than or equal to -5 mmol/l in association with a plasma lactate more than or equal to 3.0 mmol/l
g. acute hepatic failure, defined by at least two of the following criteria, in absence of primary underlying hepatic disease:
i. serum bilirubin concentration more than 43 µmol/l (2.5 mg/dl)
ii. serum Alanine Aminotransferase (ALAT)/Aspartate Aminotransferase (ASAT) concentration more than twice the upper limit of normal range
iii. PT more than 1.5 times the control value or an International Normalised Ratio (INR) more than 1.5 in the absence of systemic anticoagulation
5. Written informed consent obtained
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
32
Participant exclusion criteria
1. Pregnant or lactating women
2. Known Human Immunodeficiency Virus (HIV) seropositive patients
3. Patients receiving immunosuppressive therapy or high doses of glucocorticosteroids (defined as more than 1 mg/kg/day) equivalent to prednisone 1 mg/kg/day
4. Patients expected to have rapidly fatal disease within 24 hours
5. Known confirmed gram-positive sepsis
6. Known confirmed fungal sepsis
7. Chronic renal failure requiring haemodialysis or peritoneal dialysis
8. Acute pancreatitis with no established source of infection
9. Patients not expected to survive for 28 days due to other medical conditions such as end-stage neoplasm or other diseases
10. Participation in another investigational study within 90 days prior to start of the study which might interfere with this study
11. Previous administration of CIAP
12. Known allergy for cow milk
Recruitment start date
01/08/2004
Recruitment end date
01/03/2006
Locations
Countries of recruitment
Netherlands
Trial participating centre
Rumpsterweg 6
Bunnik
3981 AK
Netherlands
Sponsor information
Organisation
AM-Pharma B.V. (Netherlands)
Sponsor details
Rumpsterweg 6
Bunnik
3981 AK
Netherlands
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
AM-Pharma B.V. (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2009 results in http://www.ncbi.nlm.nih.gov//pubmed/19114895