A Safety, Tolerability, Efficacy and QoL Study of Human recAP in the Treatment of Patients With SA-AKI
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury
Intervention: recAP; Placebo
Intervention description: One hour infusions once daily for three days; 1 hour IV infusion once daily for 3 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 301.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: SA-AKI; Sepsis; AKI; Recombinant Alkaline Phosphatase; recAP

Summary:

      The purpose of this study is to determine whether recombinant Alkaline Phosphatase (recAP) is
      effective and save, and to determine the most effective dose, in the treatment of patients
      with acute kidney injury caused by sepsis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Informed Consent Form (patient, legal representative or independent
             investigator)

          2. Age 18 to 85 years, inclusive

          3. Is admitted to the ICU or Intermediate Care Unit

          4. Has diagnosis of sepsis (< 96 hrs prior to first study drug), according to criteria
             defined by the American College of Chest Physicians/Society of Critical Care Medicine:

               1. Has a proven or strongly suspected bacterial infection.

               2. Has at least 2 of 4 SIRS criteria 72 hrs < screening and 96 hrs < first study
                  drug

          5. First diagnosis of AKI: AKI Stage 1 or greater, according to the AKIN criteria
             (time-window adjusted):

               1. Increase in serum creatinine > 26.2 µmol/L (0.30 mg/dL) in 48 hrs prior to
                  screening, or

               2. Increase in serum creatinine to > 150% (> 1.5-fold) from reference creatinine
                  value in 48 hrs prior to screening

               3. Urinary output < 0.5 mL/kg/h for > 6 hours following adequate fluid resuscitation

          6. Continuing AKI needs to be confirmed by a confirmative fluid corrected serum
             creatinine measure, or

          7. When the AKI diagnosis was made according to the AKIN urine output criteria (urinary
             output < 0.5 mL/kg/h for > 6 hours), the oliguria or anuria should still meet the AKIN
             urine output criteria prior to randomization.

        Exclusion Criteria:

          1. Woman of childbearing potential with a positive pregnancy test, pregnant, or
             breastfeeding.

          2. Weighs more than 115 kg (253 lb).

          3. Has life support limitations.

          4. Is known to be human immunodeficiency virus positive.

          5. Has urosepsis.

          6. Is already on dialysis (RRT) or anticipated to receive RRT within 24 hours after study
             drug dosing due to the underlying disease.

          7. Is receiving immunosuppressant treatment or is on chronic high doses of steroids
             equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant
             patients. Patients with septic shock treated with hydrocortisone (e.g., 3 × 100 mg)
             can be included.

          8. Is expected to have rapidly fatal outcome (within 24 hours).

          9. Has known, confirmed fungal sepsis.

         10. Has advanced chronic liver disease, confirmed by a Child-Pugh score of 10 to 15.

         11. Has acute pancreatitis with no established source of infection.

         12. Has participated in another investigational study within 30 days prior to enrollment.

         13. Is not expected to survive for 28 days due to medical conditions other than SA AKI,
             including cancer, end-stage cardiac disease, cardiac arrest requiring cardiopulmonary
             resuscitation or with pulseless electrical activity or asystole within the past 30
             days, end stage lung disease, and end stage liver disease.

         14. Has known prior history of Chronic Kidney Disease with a documented estimated
             Glomerular Filtration Rate (eGFR) < 60 mL/min by Modification of Diet in Renal Disease
             MDRD or CKD-EPI formula, known GFR < 60 mL/min, or a known history of persistent
             creatinine level > 150 µmol/L (1.70 mg/dL) for reasons other than the current sepsis
             condition.

         15. Has diagnosis of malaria or other parasite infections.

         16. Has burns on > 20% of body surface.

         17. Has had AKI diagnosis according to inclusion criteria > 24 hours prior to study drug
             administration.

         18. Is anticipated to be treated with non-continuous RRT from Day 1 to Day 7.

         19. During Day 1 to Day 7 continuous RRT is anticipated to be started or stopped not
             according to per protocol criteria.

         20. The AKI is most likely attributable to other causes than sepsis, such as nephrotoxic
             drugs and renal perfusion-related.

         21. Improvement in serum creatinine of at least 0.30 mg/dL or (26.2 µmol/L) prior to
             administration of the study drug.

         22. Patients who use nephrotoxic medication and who fulfill the SA-AKI inclusion criteria
             at screening are not eligible if the use of this nephrotoxic medication is to continue
             when alternative, medically appropriate, non-nephrotoxic medication is available.

         23. Has a history of known IV drug abuse.

         24. Is an employee or family member of the investigator or study site personnel.

         25. Has active hematological malignancy.