Biomarker-guided Intervention to Prevent Acute Kidney Injury

Acute Kidney Injury Clinical Trial

— BigpAK-2  

Official title:

Biomarker- Guided Intervention to Prevent Acute Kidney Injury After Major Surgery. A Prospective Randomized Controlled Multicenter Trial (BigpAK-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04647396
• Other study ID #: 07-AnIt-20
• Status: Recruiting
• Phase: N/A
• Start date: November 17, 2020
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: University Hospital Muenster
• Contact: Zarbock, MD
• Phone: +49-251-8347252
• Email: aki[@]anit.uni-muenster.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1302
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

Other:
• 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 discontinuation of all nephrotoxic drugs when possible optimization of volume status and hemodynamic parameters (consideration of a functional hemodynamic monitoring) close monitoring of serum creatinine, fluid balance and urinary output avoidance of hyperglycemia considerations of alternatives to radiocontrast agents discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the perioperative period avoidance of HES, gelatin, and chlorid-rich solutions

Locations

Country	Name	City	State
Belgium	Clinical Research Department, Centre Hospitalier Universitaire Brugmann	Brussels
France	Centre Hospitalier Universitaire de Angers	Angers
France	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
Germany	Department of Anesthesiology and Intensive Care Medicine, University Hospital Augsburg	Augsburg
Germany	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 Nephrology, Heidelberg University Hospital	Heidelberg
Germany	Department of Anesthesiology and Intensive Care Medicine, Medical Faculty and University Hospital Cologne, University of Cologne	Köln
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
Italy	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	Firenze
Italy	Department of Anesthesiology and Intensive Care, IRCCS Humanitas Clinical and Research Hospital	Milan
Italy	Santa Chiara Regional Hospital, APSS Trento	Trento
Italy	Department of Anesthesiology and Intensive Care, San Bortolo Hospital	Vicenza
Netherlands	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
Spain	Department of Anaesthesiology and Intensive Care Medicine, Parc de Salut Mar	Barcelona
Spain	Department of Anesthesiology and Critical Care, University Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Igualada	Barcelona
Spain	Department of Anesthesia, Hospital Juan Ramon Jimenez	Huelva
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	Sevilla
Spain	Servicio de Anestesiologia, Hospital Universitario y Politécnico La Fe	Valencia
Switzerland	Adult Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
United Kingdom	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 Anesthetics, King's College Hospital, Denmark Hill	London
United Kingdom	Department of Critical Care, King's College London, Guy's & St Thomas' Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Muenster	BioMérieux

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurence of moderate or severe AKI		72 hours after start of intervention
Secondary	Adherence to the implementation of the KDIGO-bundle	Number of patients in whom; Nephrotoxic agents were discontinued; Optimal volume status and perfusion pressure were ensured; The use of hemodynamic monitoring was considered; Serum creatinine and urine output were considered; Hyperglycemia was avoided; Alternatives to radiocontrast were considered	72 hours after start of intervention
Secondary	Severity of AKI	Severity of AKI as defined by the KDIGO guidelines based on creatinine or urine output parameter: Stage 1 Creatinine: 1.5-1.9 times baseline OR > 0.3 mg/dl (> 26.5 mmol/l) increase and/or urine output < 0.5 ml/kg/h for 6-12 hours; Stage 2 Creatinine: 2.0-2.9 times baseline and/or urine output < 0.5 ml/kg/h for >= 12 hours; Stage 3 Creatinine: 3.0 times baseline OR Increase in serum creatinine to >= 4.0 mg/dl (>= 353.6 mmol/l) OR Initiation of renal replacement therapy OR, In patients < 18 years, decrease in eGFR to < 35 ml/min per 1.73 m2 and/or urine output < 0.3 ml/kg/h for >= 24 hour	3 days after start of intervention
Secondary	Changes in biomarker values	Difference between the 12 h after initial measuring and the initial measuring [TIMP-2]*[IGFBP7] value	12 hours after start of intervention
Secondary	Free-days of mechanical ventilation		up to 3 days after start of intervention
Secondary	Free-days of vasopressors		up to 3 days after start of intervention
Secondary	Need of renal replacement therapy		up to 30 days after start of intervention
Secondary	Need of renal replacement therapy		up to 90 days after start of intervention
Secondary	Duration of renal replacement therapy		up to 30 days after start of intervention
Secondary	Duration of renal replacement therapy		up to 90 days after start of intervention
Secondary	Renal recovery	renal recovery is defined as complete recovery: serum creatinine levels < 0.5 mg/dl higher than baseline serum creatinine (creatinine level before surgery), partial recovery: serum creatinine > 0.5 mg/dl higher than baseline but not dialysis-dependence; non-recovery: patients who remained dialysis dependent	up to 90 days after start of intervention
Secondary	Mortality		30 days after start of intervention
Secondary	Mortality		90 days after start of intervention
Secondary	ICU and hospital stay		up to 90 days after start of intervention (until discharge)
Secondary	Major adverse kidney events (MAKE)	- major adverse kidney events consisting of mortality, dialysis dependency persistent renal dysfunction (defined as serum creatinine = 2x to baseline value at hospital discharge)	up to 90 days after start of intervention