A Phase-II, double-blind, randomized, placebo-controlled study on the safety and early efficacy of Alkaline Phosphatase in sepsis patients with Renal Failure.

• Patients >=18 years and <=80 years.
• Proven or suspected infection.
• Two out of four SIRS criteria of systemic inflammation, as follows:
• Core temperature >=38°Celsius or <=36° Celsius.
• Heart rate >=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 >=20 breaths/min, a PaCO2 <=32mmHg or the use of mechanical ventilation for an acute respiratory process.
• White-cell count >=12,000/mm3 or <=4,000/mm3 or a differential count showing >10 percent immature neutrophils.
• Acute renal failure, defined as - a 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 >= 26.2 umol/l (0.3mg/dl) or increase to >= 150% (>=1.5 fold) from baseline in the previous 48 hours (in the abscence of primary underlying renal disease and where baseline creatinine is less than 150umol/l) OR -minimally a stage 1 Kidney Injury according to AKIN Urine utput criteria: oliguria, defined as urine output <=0.5mL/kg/hr for >=6 hours and following adequate fluid resuscitation when applicable, in the absence of primary underlying renal disease and where baseline creatinine is less than 150 umol/l,
• patient already on renal replacement therapy (RRT, dialysis) due to renal impairment secondary to sepsis.
• Written informed consent obtained prior to any study intervention.
In addition to the above, the following common conditions may be present (not compulsory for patient qualification for enrolment):
• Acute onset of end-organ dysfunction (other than renal failure) in the preceding 12 hours unrelated to the primary septic focus and not explained by any underlying chronic disease such as:
• Sustained hypotension or organ dysfunction that is the result of sepsis and not the patient*s underlying disease or treatment, as evidenced by one or more of the following criteria for less than 12 hours:
• Systolic blood pressure <=90mmHg or mean arterial pressure <=70mmHg for at least one hour (by two or more measurements) despite adequate fluid intake, OR
• requirement for vasopressor support to maintain MAP
• Acute alteration in mental state not due to sedation or of primary underlying disease of the central nervous system.
• Acute hypoxemic respiratory failure, defined by a PaO2(/FiO2 ratio <40kPa (300mmHg) in the absence of primary underlying pulmonary disease.
• Disseminated intravascular coagulopathy defined by either:
• Platelet count <=100*109/L
• Coagulation abnormality (PT=1.2 times control or APTT=1.2 times control)
• Metabolic acidosis defined as pH*7.30 or base excess *-5mmol/L in association with a plasma lactate *3.0mmol/L
• Acute hepatic failure, defined by at least 2 of the following criteria, in absence of primary underlying hepatic disease:
• serum bilirubin concentration >43µmol/L
• serum ALAT/ASAT concentration greater than twice the upper limit of normal range
• prothrombin time >1.5 times the control value OR an International Normalized Ratio >1.5 in the absence

• Pregnant women or nursing mothers and fecund females who are not on effective contraception (chemical: pill; or mechanical: IUD)
• Known HIV (sero-positive) patients
• Patients already on dialysis (RRT) at entry
• 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.