A Safety, Tolerability, Efficacy and QoL Study of Human recAP in the Treatment of Patients With SA-AKI

NCT02182440 | Completed Phase 2 Results DMC

• 2 other identifiers: AP-recAP-AKI-02-012014-000761-40
• Study Type: interventional
• Target: 301
• Locations: 11 countries
• Sites: 58

Brief 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.

Conditions

Acute Kidney Injury

Keywords

SA-AKI; Sepsis; AKI; Recombinant Alkaline Phosphatase; recAP

Outcome Measures

Primary Outcomes (1)

• Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7)

  Primary endpoint is calculated as the average of the standardized endogenous creatinine clearance values over the first seven days between the placebo and 1.6 mg/kg recAP arm. Standardized endogenous creatinine clearance is assessed on each days from D1 to Day 7 during a 6 +/- 1 hour period and calculated in mL/min as the mean creatinine clearance over the period. The study started with 4 treatment arms of which 0.4 mg/kg recAP and the 0.8 mg/kg recAP were dropped after the interim analysis. The number of the patients in the dropped arm are respectively 30 and 32. Therefore the statistical analysis has been performed only on the placebo and 1.6 mg/kg group.

  7 days

Secondary Outcomes (1)

• Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive

  28 days

Other Outcomes (4)

• All-cause Mortality at Day 28

  Day 28

• All-cause Mortality at Day 90

  Day 90

• Number of Participants Meeting at Least One MAKE 60 Criteria

  Day 60

Study Arms (4)

Placebo

PLACEBO COMPARATOR

1 hour IV infusion once daily for 3 days

Other: Placebo

0.4 mg/kg (250 U/kg) recAP

EXPERIMENTAL

1 hour IV infusion once daily for 3 days

Biological: recAP

0.8 mg/kg (500 U/kg) recAP

EXPERIMENTAL

1 hour IV infusion once daily for 3 days

Biological: recAP

1.6 mg/kg (1000 U/kg) recAP

EXPERIMENTAL

1 hour IV infusion once daily for 3 days

Biological: recAP

Interventions

recAP BIOLOGICAL

One hour infusions once daily for three days

Also known as: Recombinant Alkaline Phosphatase

0.4 mg/kg (250 U/kg) recAP; 0.8 mg/kg (500 U/kg) recAP; 1.6 mg/kg (1000 U/kg) recAP

Placebo OTHER

1 hour IV infusion once daily for 3 days

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (patient, legal representative or independent investigator)
• Age 18 to 85 years, inclusive
• Is admitted to the ICU or Intermediate Care Unit
• 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:
• Has a proven or strongly suspected bacterial infection.
• Has at least 2 of 4 SIRS criteria 72 hrs \< screening and 96 hrs \< first study drug
• First diagnosis of AKI: AKI Stage 1 or greater, according to the AKIN criteria (time-window adjusted):
• Increase in serum creatinine \> 26.2 µmol/L (0.30 mg/dL) in 48 hrs prior to screening, or
• Increase in serum creatinine to \> 150% (\> 1.5-fold) from reference creatinine value in 48 hrs prior to screening
• Urinary output \< 0.5 mL/kg/h for \> 6 hours following adequate fluid resuscitation
• Continuing AKI needs to be confirmed by a confirmative fluid corrected serum creatinine measure, or
• 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.

You may not qualify if:

• Woman of childbearing potential with a positive pregnancy test, pregnant, or breastfeeding.
• Weighs more than 115 kg (253 lb).
• Has life support limitations.
• Is known to be human immunodeficiency virus positive.
• Has urosepsis.
• Is already on dialysis (RRT) or anticipated to receive RRT within 24 hours after study drug dosing due to the underlying disease.
• 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.
• Is expected to have rapidly fatal outcome (within 24 hours).
• Has known, confirmed fungal sepsis.
• Has advanced chronic liver disease, confirmed by a Child-Pugh score of 10 to 15.
• Has acute pancreatitis with no established source of infection.
• Has participated in another investigational study within 30 days prior to enrollment.
• 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.
• 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.
• Has diagnosis of malaria or other parasite infections.

Sponsors & Collaborators

• AM-Pharma: lead
• PPD Development, LP: collaborator

Study Sites (58)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Tampa General Hospital, Division Emergency Medicine

Tampa, Florida, 33606, United States

Location

Eastern Idaho Medical Consultants LLC

Idaho Falls, Idaho, 83404, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Texas Houston Medical School

Houston, Texas, 77030, United States

Location

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Universitätsklinik für Allgemeine und Chirurgische Intensivmedizin

Innsbruck, Tyrol, 6020, Austria

Location

Hôpital Erasme

Brussels, Brussels Capital, B-1070, Belgium

Location

CHU UCL Mont Godinne

Yvoir, Namur, B-5530, Belgium

Location

University Hospital Ghent

Ghent, Oost Vlaanderen, 9000, Belgium

Location

University Hospital Antwerpen

Antwerp, B-2650, Belgium

Location

Cliniques Universitaires Saint Luc-UCL

Brussels, 1200, Belgium

Location

CHU Brugmann

Brussels, B-1020, Belgium

Location

UZ Brussel

Brussels, B-1090, Belgium

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, South Moravian, 656 91, Czechia

Location

Oblastni nemocnice Kolin, a.s.

Kolín, 280 02, Czechia

Location

Fakultni nemocnice Plzen

Pilsen, 30460, Czechia

Location

Helsingin Yliopistollinen Keskussairaala

Helsinki, FI-00290, Finland

Location

Kuopion Yliopistollinen Sairaala

Kuopio, 70210, Finland

Location

Tampereen yliopistollinen sairaala

Tampere, 33520, Finland

Location

Hôpital Universitaire Dupuytren

Limoges, Haute-Vienne, 87042, France

Location

Hôpital Charles Nicolle

Rouen, Seine-Maritime, 76031, France

Location

Centre Hospitalier Departemental de Vendee

La Roche-sur-Yon, Vendée, 85925, France

Location

CHU Angers

Angers, 49933, France

Location

Centre Hospitalier Victor Dupouy - hopital

Argenteuil, France

Location

CHRU Nantes - Hospital

Nantes, France

Location

Hôpital Lariboisière

Paris, 75010, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67090, France

Location

University Hospital Frankfurt, Anaesthesia, Intensive Care Medicine & Pain Therapy

Frankfurt am Main, Hesse, 60590, Germany

Location

Medizinische Hochschule Hannover Hospital - Zentrum Innere Medizin - Klinik fuer Pneumologie

Hanover, Lower Saxony, 30625, Germany

Location

Universitätsmedizin Greifswald Klinik für Anästhesiologie, IntensivmedizinNotfallmedizin und Schmerzmedizin

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

Location

Universitätsklinikum Schleswig-Holstein - Klinik für Anästhesiologie und Operative Intensivmedizin

Kiel, Schleswig-Holstein, 24105, Germany

Location

Helios Klinikum Erfurt -Klinik fur Anaesthesie, Intensivmedizin und Schmerztherapie

Erfurt, Thuringia, 99089, Germany

Location

Universitatsklinikum Jena - Klinik für Anästhesiologie und Intensivmedzin

Jena, Thuringia, 07747, Germany

Location

Universitätsklinikum Hamburg Eppendorf Department Intensive Care Medicine

Hamburg, 20246, Germany

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

Radboud University Nijmegen

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, 6532 SZ, Netherlands

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, North Brabant, 5223 GZ, Netherlands

Location

VU Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Medisch Spectrum Twente

Enschede, Overijssel, 7513 ER, Netherlands

Location

Medical Center Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, South Holland, 3015 CE, Netherlands

Location

Ikazia Ziekenhuis

Rotterdam, South Holland, 3083 AN, Netherlands

Location

Gelre Ziekenhuizen - Hospital

Apeldoorn, 7334 DZ, Netherlands

Location

Hospital Universitario Germans Trias i Pujol Medicina Intensiva Hospital General,

Badalona, Barcelona, 08916, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, Catalonia, 08025, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Catalonia, 08208, Spain

Location

Hospital Mutua de Terrassa

Terrassa, Catalonia, 08221, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre, Unidad de Cuidados Intensivos Hospital General

Madrid, 28041, Spain

Location

Hospital Universitari de Tarragona Joan XXIII

Tarragona, 43007, Spain

Location

Royal Surrey County Hospital - Intensive Care Unit

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SB, United Kingdom

Location

Royal London Hospital

London, E1 1BB, United Kingdom

Location

University College London

London, NW1 2BU, United Kingdom

Location

St James University Hospital

London, United Kingdom

Location

Related Publications (2)

• Pickkers P, Mehta RL, Murray PT, Joannidis M, Molitoris BA, Kellum JA, Bachler M, Hoste EAJ, Hoiting O, Krell K, Ostermann M, Rozendaal W, Valkonen M, Brealey D, Beishuizen A, Meziani F, Murugan R, de Geus H, Payen D, van den Berg E, Arend J; STOP-AKI Investigators. Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury: A Randomized Clinical Trial. JAMA. 2018 Nov 20;320(19):1998-2009. doi: 10.1001/jama.2018.14283.

  PMID: 30357272 DERIVED

• Peters E, Mehta RL, Murray PT, Hummel J, Joannidis M, Kellum JA, Arend J, Pickkers P. Study protocol for a multicentre randomised controlled trial: Safety, Tolerability, efficacy and quality of life Of a human recombinant alkaline Phosphatase in patients with sepsis-associated Acute Kidney Injury (STOP-AKI). BMJ Open. 2016 Sep 27;6(9):e012371. doi: 10.1136/bmjopen-2016-012371.

  PMID: 27678541 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury; Sepsis

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: JAcques Arend MD, DiMD, Chief Medical Officer
• Organization: AM-Pharma B.V.

j.arend@am-pharma.com

+31302598836

Study Officials

• Jacques Arend, MD DiMD

  AM Pharma BV

  STUDY DIRECTOR

• Peter Pickkers, Prof MD. PhD

  Department Intensive Care, Radboud University Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2014
• First Posted: July 8, 2014
• Study Start: December 18, 2014
• Primary Completion: May 25, 2017
• Study Completion: September 27, 2017
• Last Updated: March 23, 2020
• Results First Posted: March 23, 2020

Record last verified: 2020-03

Locations

AU (2); FI (3); GB (5); IE (1); DE (7); NL (9); US (6); BE (7); ES (7); CZ (3); FR (8)