Biomarker-guided Intervention to Prevent Acute Kidney Injury

NCT ID: NCT04647396

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-17
• Study Completion Date: 2024-09-09

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.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Intervention group

Group Type: EXPERIMENTAL

Comprehensive Implementation of the Bundle recommended by the "Kidney Disease: Improving Global Outcomes Group" (KDIGO bundle)

Intervention Type: OTHER

Implementation of the KDIGO bundle for at least 12 hours

1. discontinuation of all nephrotoxic drugs when possible

2. optimization of volume status and hemodynamic parameters (consideration of a functional hemodynamic monitoring)

3. close monitoring of serum creatinine, fluid balance and urinary output

4. avoidance of hyperglycemia

5. considerations of alternatives to radiocontrast agents

6. discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the perioperative period

7. avoidance of HES, gelatin, and chlorid-rich solutions

Control group

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Comprehensive Implementation of the Bundle recommended by the "Kidney Disease: Improving Global Outcomes Group" (KDIGO bundle)

Implementation of the KDIGO bundle for at least 12 hours

1. discontinuation of all nephrotoxic drugs when possible

2. optimization of volume status and hemodynamic parameters (consideration of a functional hemodynamic monitoring)

3. close monitoring of serum creatinine, fluid balance and urinary output

4. avoidance of hyperglycemia

5. considerations of alternatives to radiocontrast agents

6. discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the perioperative period

7. avoidance of HES, gelatin, and chlorid-rich solutions

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMérieux

INDUSTRY

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zarbock, MD

Role: STUDY_CHAIR

University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy

Locations

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, , France

Service d´Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon

Lyon, , France

Centre Hospitalier Universitaire de Reims

Reims, , France

Department of Anaesthesiology and Intensive Care Medicine, Klinikum Bayreuth GmbH

Bayreuth, , Germany

Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum

Bochum, , Germany

Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn

Bonn, , Germany

Department of Anesthesiology, Intensive Care and Pain Medicine, Klinikum Dortmund

Dortmund, , Germany

Department of Anesthesiology and Intensive Care Medicine, University Hospital "Carl Gustav Carus", Technische Universität Dresden

Dresden, , Germany

Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine-University Duesseldorf

Düsseldorf, , Germany

Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen

Essen, , Germany

Department of Anesthesiology, University Medical Center, Georg-August-University

Göttingen, , Germany

Department of Anesthesiology, Heidelberg University Hospital

Heidelberg, , Germany

Department of Anesthesiology and Intensive Care Medicine, Philipps-University

Marburg, , Germany

Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital

Münster, , Germany

Department of Anesthesiology, Department of Anesthesiology and Critical Care, Franziskus Hospital Münster

Münster, , Germany

Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen

Tübingen, , Germany

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, , Italy

Department of Translational Medicine and for Romagna, St. Anne's Archbishop Hospital, University of Ferrara

Ferrara, , Italy

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

Florence, , Italy

Santa Chiara Regional Hospital, APSS Trento

Trento, , Italy

Department of Anesthesiology and Intensive Care, San Bortolo Hospital

Vicenza, , Italy

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

Amsterdam, , Netherlands

Department of Anaesthesiology and Intensive Care Medicine, Parc de Salut Mar

Barcelona, , Spain

Hospital de Igualada

Barcelona, , Spain

Department of Anesthesia and Perioperative Care, Infanta Leonor University Hospital

Madrid, , Spain

Department of Anesthesiology, Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital Clínico San Carlos de Madrid

Madrid, , Spain

Servicio de Anestesiologia y Reanimación, Hosp. Universitario de La Princesa

Madrid, , Spain

Department of Anaesthesiology and Surgical Critical Care, Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Adult Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, , Switzerland

Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast

Belfast, , United Kingdom

Intensive Care Unit, Royal Surrey County Hospital

Guildford, , United Kingdom

Department of Anaesthetics and Critical Care, Harefield Hospital

Harefield, , United Kingdom

Intensive Care Unit, Royal Liverpool University Hospital

Liverpool, , United Kingdom

Department of Critical Care, King's College London, Guy's & St Thomas' Hospital

London, , United Kingdom

Countries

France; Germany; Italy; Netherlands; Spain; Switzerland; United Kingdom

References

von Groote T, Danzer MF, Meersch M, Zarbock A, Gerss J; BigpAK-2 study group. Statistical analysis plan for the biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2) study: An international randomised controlled multicentre trial. Crit Care Resusc. 2024 Jun 21;26(2):80-86. doi: 10.1016/j.ccrj.2024.03.001. eCollection 2024 Jun.

Reference Type: DERIVED

PMID: 39072240 (View on PubMed)

von Groote T, Meersch M, Romagnoli S, Ostermann M, Ripolles-Melchor J, Schneider AG, Vandenberghe W, Monard C, De Rosa S, Cattin L, Rahmel T, Adamzik M, Parise D, Candela-Toha A, Haaker JG, Gobel U, Bernard A, Lumlertgul N, Fernandez-Valdes-Bango P, Romero Bhathal I, Suarez-de-la-Rica A, Larmann J, Villa G, Spadaro S, Wulf H, Arndt C, Putensen C, Garcia-Alvarez R, Brandenburger T, Siniscalchi A, Ellerkmann R, Espeter F, Porschen C, Sadjadi M, Saadat-Gilani K, Weiss R, Gerss J, Kellum J, Zarbock A; BigpAK-2 Investigators. Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial. BMJ Open. 2023 Mar 27;13(3):e070240. doi: 10.1136/bmjopen-2022-070240.

Reference Type: DERIVED

PMID: 36972972 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

07-AnIt-20

Identifier Type: -

Identifier Source: org_study_id