Sepsis-associated acute kidney injury MedDRA version: 20.0 Level: PT Classification code 10040047 Term: Sepsis System Organ Class: 10021881 - Infections and infestations MedDRA version: 23.1 Level: PT Classification code 10066593 Term: Post procedural sepsis System Organ Class: 10021881 - Infections and infestations MedDRA version: 21.1 Level: PT Classification code 10069339 Term: Acute kidney injury System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: Recombinant Human Alkaline Phosphatase, Ilofotase alfa
Product Code: recAP
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: recAP
Current Sponsor code: recAP
Other descrip
Sponsors
AM-Pharma B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for this trial, a patient must meet all of the following inclusion criteria: 1. 18 years or older. 2. In the ICU or intermediate care unit for clinical reasons. 3. Have sepsis requiring vasopressor (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, or angiotensin II) therapy, i.e.: a) suspected or proven bacterial or viral infection and b) on vasopressor therapy (=0.1 µg/kg/min norepinephrine or equivalent) for sepsis-induced hypotension for at least one hour despite adequate fluid resuscitation according to clinical judgement. Following the initial one hour on at least 0.1 µg/kg/min norepinephrine or equivalent, any dose of vasopressor counts as vasopressor therapy. 4. Have AKI according to at least one of the below Kidney Disease Improving Global Outcomes (KDIGO) criteria, a) to d): a) An absolute increase in serum or plasma creatinine (CR) by =0.3 mg/dL (=26.5 µmol/L) within 48 hours or b) A relative increase in CR to =1.5 times pre-AKI reference CR value (see Section 8.3.3.3), which is known or presumed to have occurred within prior 7 days or c) A decrease in urinary output to =65 years) yes F.1.3.1 Number of subjects for this age range 700
Exclusion criteria
Exclusion criteria: A patient who meets any of the following criteria is excluded from participation in this trial: 1. Documented CKD as specified below: a) At selected sites where enrolment of 'moderate' CKD patients is allowed, patients with 'severe' CKD defined as a pre-AKI reference eGFR 24 hours before start of trial drug. 15. No longer on vasopressor therapy at time of randomization. 16. On continuous vasopressor therapy for >72 hours before start of trial drug. 17. Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 based on the most recent available CR sample at time of screening (NOTE: will often be the sample used to diagnose AKI). eGFR should be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. In Japan, the CKD-EPI formula with Japanese coefficient should be used. If local regulations prohibit correcting for race in the calculation of eGFR, it is acceptable to use th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate an effect of recombinant human alkaline phosphatase (recAP) on 28 day all cause mortality.;Secondary Objective: - To investigate the effect of recAP on long-term Major Adverse Kidney Events (MAKE). - To investigate the effect of recAP on use of organ support, i.e., mechanical ventilation (MV), RRT, vasopressors or inotropes. - To investigate the effect of recAP on length of stay (LOS) in intensive care unit (ICU). - To investigate the effect of recAP on 90-day all-cause mortality. ;Primary end point(s): 28-day all-cause mortality. ;Timepoint(s) of evaluation of this end point: 28th day | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - MAKE 90: dead by Day 90 or on Renal Replacement Therapy (RRT) at Day 90 or =25% decline in estimated glomerular filtration rate (eGFR) on both Day 28 and Day 90 relative to the known or assumed pre-AKI reference level. - Days alive and free of organ support through Day 28, i.e., days alive with no MV, RRT, vasopressors or inotropes (with death within 28 days counting as zero days). - Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days). - Time to death through Day 90. ;Timepoint(s) of evaluation of this end point: 28th and 90th day | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Ireland, Japan, Netherlands, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactClinical Operations
AM-Pharma B.V.
Outcome results
None listed