Clinical trial NCT04647396: Biomarker-guided Intervention to Prevent Acute Kidney Injury
Official title: Biomarker- Guided Intervention to Prevent Acute Kidney Injury After Major Surgery. A Prospective Randomized Controlled Multicenter Trial (BigpAK-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Keywords: biomarker
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: BioMérieux
First posted: 2020-11-30
Enrollment: 1180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: There is no specific therapy for acute kidney injury. It is presumed that supportive measures improve the care and outcome of patients with acute kidney injury. The investigators hypothesize that the implementation of a bundle of supportive measures adapted to patients undergoing major surgery reduces the occurrence of AKI.

This randomized prospective multicenter trial is needed to investigator whether the implementation of the bundle of measures is effective to prevent AKI in high risk patients undergoing major surgery.

Detailed description: In earlier studies, interventions to treat acute kidney injury (AKI) were started after a functional damage of the kidneys was already established. However, none of the interventions had an effect in treating AKI. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines recommend implementing different measures in patients at high risk for AKI, but the evidence that the implementation of the bundle (consisting of optimization of hemodynamics and perfusion pressure, avoidance of nephrotoxins and hyperglycemia) can prevent AKI is very weak. Biomarkers can be used to identify patients at high risk for AKI after surgery (prior to the development of AKI). The cell-cycle arrest biomarkers, Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) and Insulin-like growth factor-binding protein 7 (IGFBP7), have been demonstrated to have the best predictive performance for the development of AKI after surgery as compared to other biomarkers. In addition, these biomarkers are not influenced by different co-morbidities or other clinical situations. In the BigpAK1 trial, which was a single-center trial, the authors investigated whether a biomarker-guided implementation of the KDIGO guidelines can reduce the occurrence of AKI in patients undergoing major non-cardiac surgery. The results demonstrate that the implementation of the KDIGO bundle in high risk patients for AKI (\[TIMP-2\]\*\[IGFBP7\] between 0.3 and 2) significantly reduced the occurrence of AKI compared to the standard of care group. However, this was a single center trial which needs to be confirmed in a large trial. Therefore, based on these data, a definitive, prospective, randomized controlled, multicenter study including 1302 surgical patients at high risk for AKI identified by \[TIMP-2\]\*\[IGFBP7\] will be performed.

The goal of this trial is to investigate the effect of the implementation of the KDIGO bundle in patients at high risk for AKI after major surgery compared to standard of care in the same patient population. This biomarker-guided approach (individualized therapy) enables to treat patients at high risk for AKI prior to a functional damage of the kidneys.

Eligibility criteria: Inclusion Criteria:

* Patients after major surgery who need to be admitted to the ICU
* Age \> 18 years
* \[TIMP-2\]\*\[IGFBP7\] ≥ 0.3 4-18 hours after surgery
* Inserted jugular central venous line and a urinary catheter
* Written informed consent.
* At least one additional risk factor for AKI

  1. Age \> 75 years
  2. Critical illness such as ongoing requirement of vasopressor support and/or mechanical ventilation postoperatively
  3. Pre-existing chronic kidney disease (eGFR\<60ml/min)
  4. Intraoperative use of radio contrast agents.

Exclusion Criteria:

* Pregnancy or breastfeeding
* Pre- existing high stages of chronic kidney disease (stage 4 or 5 i.e. eGFR \< 15 ml/ min)
* Kidney transplant within the last 12 month
* Known (Glomerulo-) Nephritis, interstitial nephritis or vasculitis
* Anuria at inclusion time
* Preexisting AKI
* Renal replacement therapy (RRT) within the last 90 days
* Indication for renal replacement at the time of inclusion
* Participation in another intervention trial that investigates a drug/intervention that affects kidney function
* Persons held in an institution by legal or official order
* Persons with any kind of dependency on the investigator or employed by the responsible institution or investigator

Primary outcomes:
measure: Occurence of moderate or severe AKI
timeFrame: 72 hours after start of intervention
Secondary outcomes:
measure: Adherence to the implementation of the KDIGO-bundle
timeFrame: 72 hours after start of intervention
measure: Severity of AKI
timeFrame: 3 days after start of intervention
measure: Changes in biomarker values
timeFrame: 12 hours after start of intervention
measure: Free-days of mechanical ventilation
timeFrame: up to 3 days after start of intervention
measure: Free-days of vasopressors
timeFrame: up to 3 days after start of intervention
measure: Need of renal replacement therapy
timeFrame: up to 30 days after start of intervention
measure: Need of renal replacement therapy
timeFrame: up to 90 days after start of intervention
measure: Duration of renal replacement therapy
timeFrame: up to 30 days after start of intervention
measure: Duration of renal replacement therapy
timeFrame: up to 90 days after start of intervention
measure: Renal recovery
timeFrame: up to 90 days after start of intervention
measure: Mortality
timeFrame: 30 days after start of intervention
measure: Mortality
timeFrame: 90 days after start of intervention
measure: ICU and hospital stay
timeFrame: up to 90 days after start of intervention (until discharge)
measure: Major adverse kidney events (MAKE)
timeFrame: up to 90 days after start of intervention
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand
city: Lyon
country: France
facility: Service d´Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon
city: Reims
country: France
facility: Centre Hospitalier Universitaire de Reims
city: Bayreuth
country: Germany
facility: Department of Anaesthesiology and Intensive Care Medicine, Klinikum Bayreuth GmbH
city: Bochum
country: Germany
facility: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum
city: Bonn
country: Germany
facility: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn
city: Dortmund
country: Germany
facility: Department of Anesthesiology, Intensive Care and Pain Medicine, Klinikum Dortmund
city: Dresden
country: Germany
facility: Department of Anesthesiology and Intensive Care Medicine, University Hospital "Carl Gustav Carus", Technische Universität Dresden
city: Düsseldorf
country: Germany
facility: Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine-University Duesseldorf
city: Essen
country: Germany
facility: Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen
city: Göttingen
country: Germany
facility: Department of Anesthesiology, University Medical Center, Georg-August-University
city: Heidelberg
country: Germany
facility: Department of Anesthesiology, Heidelberg University Hospital
city: Marburg
country: Germany
facility: Department of Anesthesiology and Intensive Care Medicine, Philipps-University
city: Münster
country: Germany
facility: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital
city: Münster
country: Germany
facility: Department of Anesthesiology, Department of Anesthesiology and Critical Care, Franziskus Hospital Münster
city: Tübingen
country: Germany
facility: Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Ferrara
country: Italy
facility: Department of Translational Medicine and for Romagna, St. Anne's Archbishop Hospital, University of Ferrara
city: Firenze
country: Italy
facility: Department of Health Sciences, Section of Anesthesiology, Intensive Care and Pain Medicine, University of Florence; Department of Anesthesia and Intensive Care, Section of Oncological Anesthesia and Intensive care, Azienda Ospedaliero Careggi
city: Trento
country: Italy
facility: Santa Chiara Regional Hospital, APSS Trento
city: Vicenza
country: Italy
facility: Department of Anesthesiology and Intensive Care, San Bortolo Hospital
city: Amsterdam
country: Netherlands
facility: Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Amsterdam UMC, Location Academic Medical Centre (AMC), Amsterdam, University of Amsterdam
city: Barcelona
country: Spain
facility: Department of Anaesthesiology and Intensive Care Medicine, Parc de Salut Mar
city: Barcelona
country: Spain
facility: Hospital de Igualada
city: Madrid
country: Spain
facility: Department of Anesthesia and Perioperative Care, Infanta Leonor University Hospital
city: Madrid
country: Spain
facility: Department of Anesthesiology, Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos de Madrid
city: Madrid
country: Spain
facility: Servicio de Anestesiologia y Reanimación, Hosp. Universitario de La Princesa
city: Santander
country: Spain
facility: Department of Anaesthesiology and Surgical Critical Care, Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Lausanne
country: Switzerland
facility: Adult Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV)
city: Belfast
country: United Kingdom
facility: Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast
city: Guildford
country: United Kingdom
facility: Intensive Care Unit, Royal Surrey County Hospital
city: Harefield
country: United Kingdom
facility: Department of Anaesthetics and Critical Care, Harefield Hospital
city: Liverpool
country: United Kingdom
facility: Intensive Care Unit, Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Department of Critical Care, King's College London, Guy's & St Thomas' Hospital
Study officials:
affiliation: University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy
name: Zarbock, MD
role: STUDY_CHAIR
References: