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Acute Kidney InjuryPhase 2STOP-AKINCT02182440

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

A Phase 2 study testing recAP in people with Acute Kidney Injury, run by AM-Pharma at 58 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Kidney Injury
What is being tested?
recAP
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
301 participants
Where
58 sitesin 11 countries
Study dates
18 Dec 2014to 27 Sep 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • Has burns on > 20% of body surface.
  • Has had AKI diagnosis according to inclusion criteria > 24 hours prior to study drug administration.
  • Is anticipated to be treated with non-continuous RRT from Day 1 to Day 7.
  • During Day 1 to Day 7 continuous RRT is anticipated to be started or stopped not according to per protocol criteria.
  • The AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs and renal perfusion-related.
  • Improvement in serum creatinine of at least 0.30 mg/dL or (26.2 µmol/L) prior to administration of the study drug.
  • 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.
  • Has a history of known IV drug abuse.
  • Is an employee or family member of the investigator or study site personnel.
  • Has active hematological malignancy.

Trial locations and contacts

58 sites in 11 countries.

58 sites in 11 countries

Netherlands9 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, North Brabant, 5223 GZ

  • VU Medisch Centrum

    Amsterdam, North Holland, 1081 HV

  • Gelre Ziekenhuizen - Hospital

    Apeldoorn, 7334 DZ

  • Medisch Spectrum Twente

    Enschede, Overijssel, 7513 ER

  • Medical Center Leeuwarden

    Leeuwarden, Provincie Friesland, 8934 AD

  • Radboud University Nijmegen

    Nijmegen, Gelderland, 6525 GA

  • Canisius Wilhelmina Ziekenhuis

    Nijmegen, Gelderland, 6532 SZ

  • Erasmus Medisch Centrum

    Rotterdam, South Holland, 3015 CE

  • Ikazia Ziekenhuis

    Rotterdam, South Holland, 3083 AN

Other trials in Netherlands

France8 sites

  • CHU Angers

    Angers, 49933

  • Centre Hospitalier Victor Dupouy - hopital

    Argenteuil

  • Centre Hospitalier Departemental de Vendee

    La Roche-sur-Yon, Vendée, 85925

  • Hôpital Universitaire Dupuytren

    Limoges, Haute-Vienne, 87042

  • CHRU Nantes - Hospital

    Nantes

  • Hôpital Lariboisière

    Paris, 75010

  • Hôpital Charles Nicolle

    Rouen, Seine-Maritime, 76031

  • Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67090

Other trials in France

Belgium7 sites

  • University Hospital Antwerpen

    Antwerp, B-2650

  • Hôpital Erasme

    Brussels, Brussels Capital, B-1070

  • Cliniques Universitaires Saint Luc-UCL

    Brussels, 1200

  • CHU Brugmann

    Brussels, B-1020

  • UZ Brussel

    Brussels, B-1090

  • University Hospital Ghent

    Ghent, Oost Vlaanderen, 9000

  • CHU UCL Mont Godinne

    Yvoir, Namur, B-5530

Other trials in Belgium

Germany7 sites

  • Helios Klinikum Erfurt -Klinik fur Anaesthesie, Intensivmedizin und Schmerztherapie

    Erfurt, Thuringia, 99089

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

    Frankfurt am Main, Hesse, 60590

  • Universitätsmedizin Greifswald Klinik für Anästhesiologie, IntensivmedizinNotfallmedizin und Schmerzmedizin

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Universitätsklinikum Hamburg Eppendorf Department Intensive Care Medicine

    Hamburg, 20246

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

    Hanover, Lower Saxony, 30625

  • Universitatsklinikum Jena - Klinik für Anästhesiologie und Intensivmedzin

    Jena, Thuringia, 07747

  • Universitätsklinikum Schleswig-Holstein - Klinik für Anästhesiologie und Operative Intensivmedizin

    Kiel, Schleswig-Holstein, 24105

Other trials in Germany

Spain7 sites

  • Hospital Universitario Germans Trias i Pujol Medicina Intensiva Hospital General,

    Badalona, Barcelona, 08916

  • Hospital de La Santa Creu i Sant Pau

    Barcelona, Catalonia, 08025

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

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

    Madrid, 28041

  • Corporacio Sanitaria Parc Tauli

    Sabadell, Catalonia, 08208

  • Hospital Universitari de Tarragona Joan XXIII

    Tarragona, 43007

  • Hospital Mutua de Terrassa

    Terrassa, Catalonia, 08221

Other trials in Spain

United States6 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • University of Texas Houston Medical School

    Houston, Texas, 77030

  • Eastern Idaho Medical Consultants LLC

    Idaho Falls, Idaho, 83404

  • UPMC

    Pittsburgh, Pennsylvania, 15261

  • Tampa General Hospital, Division Emergency Medicine

    Tampa, Florida, 33606

Other trials in United States

United Kingdom5 sites

  • Royal Infirmary of Edinburgh

    Edinburgh, EH16 4SB

  • Royal Surrey County Hospital - Intensive Care Unit

    Guildford, Surrey, GU2 7XX

  • Royal London Hospital

    London, E1 1BB

  • University College London

    London, NW1 2BU

  • St James University Hospital

    London

Other trials in United Kingdom

Czechia3 sites

  • Fakultni nemocnice u sv. Anny v Brne

    Brno, South Moravian, 656 91

  • Oblastni nemocnice Kolin, a.s.

    Kolín, 280 02

  • Fakultni nemocnice Plzen

    Pilsen, 30460

Other trials in Czechia

Finland3 sites

  • Helsingin Yliopistollinen Keskussairaala

    Helsinki, FI-00290

  • Kuopion Yliopistollinen Sairaala

    Kuopio, 70210

  • Tampereen yliopistollinen sairaala

    Tampere, 33520

Other trials in Finland

Austria2 sites

  • Medizinische Universität Innsbruck

    Innsbruck, Tyrol, 6020

  • Universitätsklinik für Allgemeine und Chirurgische Intensivmedizin

    Innsbruck, Tyrol, 6020

Other trials in Austria

Ireland1 site

  • St. Vincent's University Hospital

    Dublin

Other trials in Ireland

About this study

Official title: A DB Four-Arm, Parallel Group, Proof of Concept, Dose-Finding Adaptive Phase 2a/2b RCT to Investigate the Safety, Tolerability and Efficacy and Effect on QoL of Human Recombinant Alkaline Phosphatase in Patients With Sepsis-Associated AKI

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.

Read the detailed description

Design:

Adaptive trial with two stages and interim analysis

  • Stage 1: four arms; three dose groups and placebo. n=30/arm. (n=120)
  • Interim analysis based on 120 subjects, with continued recruitment, adding 11 subjects to Stage 1 safety population (n=131): to evaluate safety and select dose for stage 2
  • Stage 2: one dose group and placebo. N=85/arm. (n=170) Total n in the study: 301.

Primary objectives

  • To investigate the effect of recAP on renal function (measured creatinine clearance D1-D7 period, incidence and duration of renal replacement therapy (RRT) over 28 days, eGFR at D60 and D90) and related clinical parameters (ICU stay, Hospital stay, Mechanical ventilation over 28 days, SOFA and SAPS2 scores 28 days) in patients with SA-AKI.
  • To determine effective therapeutic dose(s) of recAP.

Secondary objectives

  • To investigate the safety and tolerability of recAP in patients with SA AKI. (assessed by independent Data Monitoring Board, adverse events over 90 days study period, laboratory values, ECG, physical examniations, vital signs, Anti Drug Antibodies)
  • To investigate the pharmacokinetic profile (PK) of recAP in a subset of patients (part 1, n=120) with SA AKI. (Population PK; AUC D1-7, Cmax, Cmin, Tmax, terminal T1/2)
  • To investigate the immunogenic potential of recAP in patients with SA AKI. (anti-drug antibodies at D14, D28, D60 and D90)
  • To investigate the effect on quality of life (using the EuroQol, EQ-5D) following study inclusion, at ICU discharge, and Day 90.

Other objectives

  • To evaluate whether specific patient groups can be identified that benefit most from recAP treatment or patient groups that are non-responders
Being tested
recAP, Placebo
Keywords
SA-AKI, Sepsis, AKI, Recombinant Alkaline Phosphatase, recAP
Medical subject headings
Acute Kidney Injury, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • recAPBiological

    Also called Recombinant Alkaline Phosphatase

    One hour infusions once daily for three days

  • PlaceboOther

    1 hour IV infusion once daily for 3 days

Study groups in NCT02182440
Study groupRoleWhat they receive
PlaceboPlacebo comparator1 hour IV infusion once daily for 3 days
Receives: Other: Placebo
0.4 mg/kg (250 U/kg) recAPExperimental1 hour IV infusion once daily for 3 days
Receives: Biological: recAP
0.8 mg/kg (500 U/kg) recAPExperimental1 hour IV infusion once daily for 3 days
Receives: Biological: recAP
1.6 mg/kg (1000 U/kg) recAPExperimental1 hour IV infusion once daily for 3 days
Receives: Biological: recAP

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 7 days

Secondary outcomes (1)

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

    During the study the days on Renal Replacement Therapy (RRT) was recorded for each patients. During the first 7 days of the study (D1 to D7 included), patients were only allowed to receive continuous RRT, thereafter patients were also allowed to receive intermittent RRT. Standardization of RRT was attempted by providing guidelines to start and stop RRT (see protocol). Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study.

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2014 (estimated)
  2. Study start18 Dec 2014
  3. Primary completion25 May 2017
  4. Study completion27 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
301 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02182440
Sponsor's protocol ID
AP-recAP-AKI-02-01
Other IDs
2014-000761-40, 2014
Acronym
STOP-AKI
Status last verified
Mar 2020
First submitted
27 Jun 2014
Last updated
23 Mar 2020
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 30357272

  • 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.

    PubMed 27678541

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing recAP in people with Acute Kidney Injury, run by AM-Pharma at 58 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in Netherlands, France, Belgium, Germany, Spain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) (time frame: 7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02182440, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2020.

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