Biomarker-guided Intervention to Prevent Acute Kidney Injury (BigpAK-2)

• ClinicalTrials.gov Identifier: NCT04647396
• Recruitment Status: Recruiting
• First Posted: November 30, 2020
• Last Update Posted: December 16, 2021
• Sponsor: University Hospital Muenster
• Collaborator: BioMérieux
• Information provided by (Responsible Party): University Hospital Muenster

Study Description

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 non-cardiac 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 non-cardiac surgery.

Condition or disease	Intervention/treatment	Phase
Acute Kidney Injury	Other: Comprehensive Implementation of the Bundle recommended by the "Kidney Disease: Improving Global Outcomes Group" (KDIGO bundle)	Not Applicable

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 non-cardiac 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1302 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Biomarker- Guided Intervention to Prevent Acute Kidney Injury After Major Non-Cardiac Surgery. A Prospective Randomized Controlled Multicenter Trial (BigpAK-2)
• Actual Study Start Date: November 17, 2020
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention group	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
No Intervention: Control group

Outcome Measures

Primary Outcome Measures :

1. Occurence of moderate or severe AKI [ Time Frame: 72 hours after start of intervention ]

Secondary Outcome Measures :

1. Adherence to the implementation of the KDIGO-bundle [ Time Frame: 72 hours after start of intervention ]

   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
2. Severity of AKI [ Time Frame: 3 days after start of intervention ]

   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. Changes in biomarker values [ Time Frame: 12 hours after start of intervention ]
   Difference between the 12 h after initial measuring and the initial measuring [TIMP-2]*[IGFBP7] value
4. Free-days of mechanical ventilation [ Time Frame: up to 3 days after start of intervention ]
5. Free-days of vasopressors [ Time Frame: up to 3 days after start of intervention ]
6. Need of renal replacement therapy [ Time Frame: up to 30 days after start of intervention ]
7. Need of renal replacement therapy [ Time Frame: up to 90 days after start of intervention ]
8. Duration of renal replacement therapy [ Time Frame: up to 30 days after start of intervention ]
9. Duration of renal replacement therapy [ Time Frame: up to 90 days after start of intervention ]
10. Renal recovery [ Time Frame: up to 90 days after start of intervention ]
    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
11. Mortality [ Time Frame: 30 days after start of intervention ]
12. Mortality [ Time Frame: 90 days after start of intervention ]
13. ICU and hospital stay [ Time Frame: up to 90 days after start of intervention (until discharge) ]
14. Major adverse kidney events (MAKE) [ Time Frame: up to 90 days after start of intervention ]
    - major adverse kidney events consisting of mortality, dialysis dependency persistent renal dysfunction (defined as serum creatinine ≥ 2x to baseline value at hospital discharge)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients after major non-cardiac 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

Contacts and Locations

Contacts

Contact: Zarbock, MD; +49-251-8347252; aki@anit.uni-muenster.de

Contact: Meersch, MD; aki@anit.uni-muenster.de

Locations

Germany

Universitätsklinikum Knappschaftskrankenhaus Bochum; Recruiting

Bochum, Germany

University Hospital Münster; Recruiting

Münster, Germany, 48329

St. Franziskus-Hospital Münster; Recruiting

Münster, Germany

Spain

Hospital Infanta Leonor; Recruiting

Madrid, Spain

Hospital Ramón y Cajal; Recruiting

Madrid, Spain

Hospital Valdecilla; Recruiting

Santander, Spain

Sponsors and Collaborators

University Hospital Muenster

BioMérieux

Investigators

• Study Chair: Zarbock, MD; University Hospital Muenster, Dept. of Anesthesiology, Intensive Care Medicine and Pain Therapy

More Information

• Responsible Party: University Hospital Muenster
• ClinicalTrials.gov Identifier: NCT04647396
• Other Study ID Numbers: 07-AnIt-20
• First Posted: November 30, 2020
• Last Update Posted: December 16, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Muenster:

biomarker

Additional relevant MeSH terms:

Acute Kidney Injury; Wounds and Injuries; Renal Insufficiency; Kidney Diseases; Urologic Diseases