(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI

A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI

Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis.

The study has three distinct SA-AKI trial populations:

1. The main trial population: Patients with a pre-AKI reference eGFR ≥45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization.
2. A 'moderate' CKD population: Patients with a pre-AKI reference eGFR ≥25 and <45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization.
3. A Corona Virus Disease 2019 (COVID-19) population: Patients with proven or suspected SARS-CoV-2 at time of randomization with or without 'moderate' CKD. For patients in this population, COVID-19 should be the main cause of SA-AKI.

In the main study population approximately 1400 patients will be enrolled and in the two cohorts with moderate CKD and COVID-19 each up to 100 patients.

There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.

Study Overview

• Status: Terminated
• Conditions: Acute Kidney Injury Due to Sepsis
• Intervention / Treatment: Other: Placebo; Biological: Recombinant human alkaline phosphatase

Detailed Description

Sepsis is the leading cause of acute kidney injury (AKI) and a major cause of death. Patients with SA-AKI have a high mortality and morbidity and are at risk of developing chronic kidney disease. AP is a homodimeric endogenous enzyme present in many cells and organs, e.g., intestines, placenta, liver, bone, kidney, and granulocytes. It exerts detoxifying effects through dephosphorylation of endotoxins; pathogen associated molecular pattern molecules (PAMPS e.g., lipopolysaccharide) and damage-associated molecular pattern molecules (DAMPS e.g., adenosine tri- and di-phosphate). In animal models of sepsis and AKI, administration of AP attenuates the inflammatory response, improves renal function and/or reduces mortality.

AM-Pharma B.V. is developing AP as a novel, recombinant chimeric human AP medicinal product, called recAP, to be used as an intravenous infusion for the treatment of SA-AKI. In the Phase 2 trial STOP-AKI, a survival benefit was observed in the two highest dose groups, 0.8 mg/kg and 1.6 mg/kg groups, compared to the placebo group. There were no safety or tolerability concerns for any of the doses tested (0.4, 0.8 and 1.6 mg/kg). The 1.6 mg/kg recAP dose was selected for this Phase 3 trial based on the significant survival benefit observed. PK/PD simulations also confirmed this dose to have the most pronounced treatment effect.

The primary objective of this Phase 3 trial is to confirm the mortality benefit seen in STOP-AKI by demonstrating a reduction in 28 day all cause mortality in patients with SA-AKI treated with 1.6 mg/kg recAP.

• Study Type: Interventional
• Enrollment (Actual): 676
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Bendigo, Australia, 3550
    • Bendigo Hospital
  • Footscray, Australia, 3011
    • Footscray Hospital
  • Melbourne, Australia, 3084
    • Austin Hospital
  • New Lambton Heights, Australia, 2305
    • John Hunter Hospital
  • Saint Albans, Australia, 3021
    • Sunshine Hospital ICU - Western Hospital
  • Southport, Australia, 4215
    • Gold Coast University Hospital (GCUH)
• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaet Graz - Klinik fuer Innere Medizin
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck - Universitaetsklinik fuer Innere Medizin I
• Belgium
  • Brussels, Belgium, 1020
    • Centre Hospitalier Universitaire Brugmann
  • Charleroi, Belgium, 6042
    • Centre Hospitalier Universitaire (CHU) de Charleroi - Hopital Civil Marie Curie
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Jette, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • La Louvière, Belgium, 7100
    • Hopital De Jolimont
  • Ottignies, Belgium, 1340
    • Clinique Saint-Pierre- Ottignies
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Yvoir, Belgium, 5530
    • CHU UCL Namur - Mont-Godinne
• Canada
  • Calgary, Canada, T1Y 6J4
    • Peter Lougheed Centre
  • Calgary, Canada, T2N 2T9
    • Foothills Medical Centre
  • Calgary, Canada, T2V 1P9
    • Rockyview General Hospital
  • Calgary, Canada, T3M 1M4
    • Alberta Health Services - South Health Campus Hospital
  • Ottawa, Canada, K1H 8L6
    • The Ottawa Hospital - General Campus
  • Ottawa, Canada, K1Y 4E9
    • The Ottawa Hospital - Civic Campus
  • Québec, Canada, G1J 1Z4
    • Hôpital de l'Enfant-Jésus
  • Vancouver, Canada, V6Z 1Y6
    • St. Paul's Hospital
  • Victoria, Canada, V8R 1J8
    • Royal Jubilee Hospital (RJH)
  • Victoria, Canada, V8R 1J8
    • Victoria General Hospital (VGH)
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Herning, Denmark, 7400
    • Herning Regional Hospital
  • Hillerød, Denmark, 3400
    • Nordsjællands Hospital
  • København, Denmark, 2100
    • Rigshospitalet
  • Køge, Denmark, 4600
    • Sjaellands Universitetshospital, Koge - Kardiologisk Afdeling
  • Odense C, Denmark, 5000
    • Odense Universitetshospital
  • Randers, Denmark, 8930
    • Regionshospitalet Randers
  • Slagelse, Denmark, 4200
    • Slagelse Sygehus
  • Viborg, Denmark, 8800
    • Hospitalsenhed Midt
• Finland
  • Helsinki, Finland, 290
    • Helsinki University Central Hospital (HUCH)
  • Tampere, Finland, 33521
    • Tampere University Hospital
  • Turku, Finland, 20521
    • Turku University Hospital (TYKS)
• France
  • Angers Cedex, France, 49933
    • Centre Hospitalier Universitaire D'Angers
  • Argenteuil Cedex, France, 95107
    • Centre Hospitalier D'Argenteuil
  • Béthune, France, 62408
    • Centre Hospitalier de Bethune Germon et Gauthier
  • Cergy-Pontoise, France, 95303
    • Centre Hospitalier René-Dubos
  • Dijon, France, 21079
    • CHU Dijon - Hôpital François Mitterrand
  • La Roche-sur-Yon, France, 85000
    • Centre Hospitalier Départemental de Vendée - Les Oudairies
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Bicêtre
  • Le Mans, France, 72000
    • Centre Hospitalier du Mans
  • Limoges Cedex, France, 87000
    • CHU Limoges - Hopital Dupuytren
  • Nancy, France, 54000
    • CHU de Nancy
  • Nantes, France, 44000
    • CHU de Nantes - Hotel-Dieu
  • Nîmes cedex 9, France, 30029
    • CHU de Nîmes - Hopital Universitaire Caremeau
  • Orléans, France, 45067
    • Hopital La Source
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Strasbourg, France, 67091
    • Hôpitaux Universitaires de Strasbourg - Hôpital Civil
  • Tours cedex 9, France, 37044
    • CHRU de Tours - Hôpital Bretonneau
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf (UKE)
  • Jena, Germany, 7747
    • University Hospital Jena - Klinik fur Neurologie
  • Leipzig, Germany, 4103
    • Universitaetsklinikum Leipzig - Klinik und Poliklinik fuer Gastroenterologie und Rheumatologie
  • Münster, Germany, 48149
    • University Hospital Münster
• Ireland
  • Dublin, Ireland, D08 NHY1
    • St. James's Hospital
  • Dublin, Ireland, D24NR0A
    • Tallaght University Hospital
  • Dublin, Ireland, Dublin 4
    • St. Vincent's University Hospital
  • G
    • Galway, G, Ireland, H91 YR71
      • National University of Ireland, Galway
• Japan
  • Hachioji-Shi, Japan, 193-0998
    • Tokyo Medical University Hachioji Medical Center
  • Hiroshima-shi, Japan
    • Hiroshima University Hospital
  • Izuka-shi, Japan, 820-8505
    • Aso Iizuka Hospital
  • Izumisano-Shi, Japan, 598-8577
    • Rinku General Medical Center
  • Kashihara-Shi, Japan, 634-8522
    • Nara Medical University Hospital
  • Kumamoto-Shi, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Omihachiman-Shi, Japan, 523-0082
    • Omihachiman Community Medical Center
  • Osaka-Shi, Japan, 534-0021
    • Osaka City General Hospital
  • Osaka-shi, Japan, 543-0035
    • Osaka Police Hospital
  • Toyoake-Shi, Japan, 470-1192
    • Fujita Health University Hospital
  • Yokohama-Shi, Japan, 245-8575
    • National Hospital Organization - Yokohama Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam UMC - VUmc
  • Ede, Netherlands, 6716 RP
    • Ziekenhuis Gelderse Vallei
  • Enschede, Netherlands, KZ 7512
    • Medisch Spectrum Twente
  • Heerlen, Netherlands, Heerlen
    • Zuyderland Medisch Centrum, Heerlen
  • Nijmegen, Netherlands, 6532 SZ
    • Canisius-Wilhelmina Ziekenhuis
  • Nijmegen, Netherlands, 6500 HB
    • Radboud UMC
  • NB
    • 's-Hertogenbosch, NB, Netherlands, 5223 GZ
      • Jeroen Bosch Ziekenhuis lokatie GZG
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Auckland, New Zealand, 2025
    • Middlemore Clinical Trials
  • Christchurch, New Zealand, 8140
    • Christchurch Hospital
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital
  • Grafton, New Zealand, 1023
    • Auckland City Hospital
  • Hastings, New Zealand, 4172
    • Hawke's Bay Hospital Soldiers' Memorial
  • Rotorua, New Zealand, 3046
    • Lakes District Health Board - Rotorua Hospital
  • WGN
    • Wellington, WGN, New Zealand, 6021
      • Wellington Hospital
• Spain
  • Badalona, Spain, 8916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 8003
    • Hospital del Mar
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 8907
    • Hospital Universitari de Bellvitge (IDIBELL)
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Sabadell, Spain, 8208
    • Parc Tauli Sabadell Hospital Universitari
  • Terrassa, Spain, 8221
    • Universitat de Barcelona - Hospital Universitari Mutua Terrassa (HUMT)
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital
  • Plymouth, United Kingdom, PL6 8DH
    • Plymouth Hospitals NHS Trust - Derriford Hospital
  • LND
    • London, LND, United Kingdom, NW1 2BU
      • University College London Hospitals NHS Foundation Trust - University College Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5057
      • The University of Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90095-8358
      • Ronald Reagan UCLA Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037-2342
      • The George Washington University Medical Faculty Associates - Anesthesiology
  • Georgia
    • Atlanta, Georgia, United States, 30322-1007
      • Emory Clinical Cardiovascular Research Institute
  • Illinois
    • Glenview, Illinois, United States, 60026-1301
      • Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore Medical Group - Bannockburn
  • Kentucky
    • Lexington, Kentucky, United States, 40508-3215
      • University of Kentucky College of Medicine (UKCM)
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico School of Medicine
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Institute
    • Columbus, Ohio, United States, 43210
      • The Ohio State University - Dorothy M. Davis Heart and Lung Research Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-3108
      • UPMC CancerCenter at Magee - Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15213-3108
      • UPMC Presbyterian
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0817
      • University of Virginia Health System
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Froedtert & the Medical College of Wisconsin Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.:

   1. suspected or proven bacterial or viral infection. and
   2. 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.

   The combination of a) and b) automatically ensures that patients fulfill the Sepsis 3 criteria as 0.1 µg/kg/min norepinephrine corresponds to a score of +4 on the Cardiovascular sub-score of the SOFA score.

4. Have AKI according to at least one of the below KDIGO criteria, a to d:

   1. An absolute increase in serum or plasma creatinine (CR) by ≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours.

      or

   2. A relative increase in CR to ≥1.5 times the pre-AKI reference CR value which is known or presumed to have occurred within prior 7 days.

      or

   3. A decrease in urinary output to <0.5 mL/kg/hour for a minimum of 6 hours following adequate fluid resuscitation.

   or d) If the patient does not have a known history of CKD and there is no pre-AKI reference CR value available from the past 12 months available from the past 12 months: a CR value greater or equal to the levels presented in Table 1, with the increase in CR presumed to have occurred within prior 7 days.

5. Provision of signed and dated ICF in accordance with local regulations.

Exclusion Criteria:

1. a) At sites where enrolment of 'moderate' CKD patients is allowed, patients with 'severe' CKD defined as a pre-AKI reference eGFR <25 mL/min/1.73 m2 are excluded.

   • For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as ≥25 mL/min/1.73 m2.

   • For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 25-60 mL/min/1.73 m2 can also be used to rule out 'severe' CKD.

     b) At sites where enrolment of 'moderate' CKD patients is NOT allowed, patients with 'moderate' and 'severe' CKD defined as a pre-AKI reference eGFR <45 mL/min/1.73 m2 are excluded.

   • For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as ≥45 mL/min/1.73 m2.
   • For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 45-60 mL/min/1.73 m2 can also be used to rule out 'moderate' and 'severe' CKD.
2. Advanced chronic liver disease, defined as a Child-Pugh score of 10 to 15 (Class C).
3. Acute pancreatitis without proven infection.
4. Urosepsis related to suspected or proven urinary tract obstruction.
5. Main cause of AKI not sepsis.
6. Proven or suspected SARS-CoV-2 infection. NOTE: This exclusion criterion does not apply to patients in the COVID-19 population, in which COVID-19 should be the main cause of SA-AKI.
7. Severe burns requiring ICU treatment.

8. Severely immunosuppressed, e.g. due to:

   • hematopoietic cell transplantation within past 6 months prior to Screening or acute or chronic graft-versus-host disease
   • solid organ transplantation
   • leukopenia not related to sepsis, i.e., preceding sepsis
   • Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
   • receiving chemotherapy within 30 days prior to Screening.
9. At high risk of being LTFU, e.g., due to known current or recent (within the last 6 months) IV drug abuse or known to be homeless.
10. Limitations to use of mechanical ventilation (MV), RRT or vasopressors and inotropes (NOTE: limitation of cardiopulmonary resuscitation (CPR) only is not an exclusion criterion).
11. Previous administration of recAP.
12. Use of a non-marketed drug within the last month or concurrent or planned participation in a clinical trial for a non-marketed drug or device. (NOTE: Co-enrollment or concurrent participation in observational, non-interventional trials using no protocolized treatments or procedures are always allowed. Co-enrollment or concurrent participation in trials using protocolized treatments or procedures, e.g. blood draws, requires pre-approval by the TSC).
13. Current or planned extracorporeal membrane oxygenation (ECMO).
14. On RRT >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 the formula without correcting for race.

18. Not feasible to start trial drug within:

    1. 48 hours from AKI diagnosis, when AKI diagnosis precedes start of vasopressor therapy.

       or

    2. 24 hours from AKI diagnosis, when AKI is diagnosed after start of vasopressor therapy.
19. Pregnant or nursing women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; matching placebo	Other: Placebo; Placebo
Experimental: active; recombinant human alkaline phosphatase 1.6mg/kg 3 daily 1 hour infusions	Biological: Recombinant human alkaline phosphatase; patients with SA-AKI are randomly assigned in a 1:1 ratio to either placebo or 1.6 mg/kg recAP.; Other Names: ilofotase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day All-cause Mortality: Main Trial Population	To demonstrate an effect of recAP on 28 day all cause mortality	28 days
28-day All-cause Mortality: Moderate Chronic Kidney Disease Population	To demonstrate an effect of recAP on 28 day all cause mortality	28 days
28-day All-cause Mortality: COVID-19 Population	To demonstrate an effect of recAP on 28 day all cause mortality	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Kidney Events 90: Main Trial Population	Major adverse kidney events (MAKE) 90: dead by Day 90 or on Renal Replacement Therapy (RRT) at Day 90 or greater than or equal to 25% decline in estimated glomerular filtration rate (eGFR) on both Day 28 and Day 90 relative to the known or assumed pre-acute kidney injury reference level.	90 Days
Major Adverse Kidney Events 90: Moderate Chronic Kidney Disease Population	Major adverse kidney events (MAKE) 90: dead by Day 90 or on Renal Replacement Therapy (RRT) at Day 90 or greater than or equal to 25% decline in estimated glomerular filtration rate (eGFR) on both Day 28 and Day 90 relative to the known or assumed pre-acute kidney injury reference level.	90 Days
Major Adverse Kidney Events 90: COVID-19 Population	Major adverse kidney events (MAKE) 90: dead by Day 90 or on Renal Replacement Therapy (RRT) at Day 90 or greater than or equal to 25% decline in estimated glomerular filtration rate (eGFR) on both Day 28 and Day 90 relative to the known or assumed pre-acute kidney injury reference level.	90 Days
Major Adverse Kidney Events Through Day 90: Combined Population	Major Adverse Kidney Events through day 90 (MAKE90A) : death until day 90; greater than 25% drop in estimated glomerular filtration rate at Day 90; on renal replacement therapy (RRT) at day 90 OR on RRT through Day 28	90 Days
Days Alive and Free of Organ Support Through Day 28: Main Trial Population	Days alive and free of organ support through Day 28, ie, days alive with no mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors, or inotropes (with death within 28 days counting as zero days)	28 days
Days Alive and Free of Organ Support Through Day 28: Moderate Chronic Kidney Disease Population	Days alive and free of organ support through Day 28, ie, days alive with no mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors, or inotropes (with death within 28 days counting as zero days)	28 days
Days Alive and Free of Organ Support Through Day 28: COVID-19 Population	Days alive and free of organ support through Day 28, ie, days alive with no mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors, or inotropes (with death within 28 days counting as zero days)	28 days
Days Alive and Out of the ICU Through Day 28: Main Trial Population	Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).	28 days
Days Alive and Out of the ICU Through Day 28: Moderate Chronic Kidney Disease Population	Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).	28 days
Days Alive and Out of the ICU Through Day 28: COVID-19 Population	Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).	28 days
90-day All Cause Mortality: Main Trial Population	90-Day all-cause mortality	90 days
90-day All Cause Mortality: Moderate Chronic Kidney Disease Population	90-Day all-cause mortality	90 days
90-day All Cause Mortality: COVID-19 Population	90-Day all-cause mortality	90 days

Collaborators and Investigators

• Sponsor: AM-Pharma
• Investigators: Study Director: A Legters, AM-Pharma

Publications and helpful links

General Publications

• Pickkers P, Angus DC, Bass K, Bellomo R, van den Berg E, Bernholz J, Bestle MH, Doi K, Doig CJ, Ferrer R, Francois B, Gammelager H, Pedersen UG, Hoste E, Iversen S, Joannidis M, Kellum JA, Liu K, Meersch M, Mehta R, Millington S, Murray PT, Nichol A, Ostermann M, Pettila V, Solling C, Winkel M, Young PJ, Zarbock A; REVIVAL investigators. Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL). Intensive Care Med. 2024 Jan;50(1):68-78. doi: 10.1007/s00134-023-07271-w. Epub 2024 Jan 3. Erratum In: Intensive Care Med. 2024 Apr;50(4):614-615.
• Pickkers P, Angus DC, Arend J, Bellomo R, van den Berg E, Bernholz J, Bestle M, Broglio K, Carlsen J, Doig CJ, Ferrer R, Joannidis M, Francois B, Doi K, Kellum JA, Laterre PF, Liu K, Mehta RL, Murray PT, Ostermann M, Pettila V, Richards S, Young P, Zarbock A, Kjolbye AL. Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury. BMJ Open. 2023 Apr 3;13(4):e065613. doi: 10.1136/bmjopen-2022-065613.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Actual): August 18, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sepsis; Acute Kidney Injury
• Other Study ID Numbers: AP-recAP-AKI-03-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No