Development of an Innovative Clinico-biological Score for the Early Detection of Acute Renal Failure Associated With Cardiac Surgery.

Acute Kidney Injury Clinical Trial

— DETECT-AKI  

Official title:

Elaboration d'un Score Clinico-biologique Innovant Pour la détection précoce de l'Insuffisance rénale aiguë associée à la chirurDevelopment of an Innovative Clinico-biological Score for the Early Detection of Acute Renal Failure Associated With Cardiac Surgery. Gie Cardiaque. Monocentric Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05283213
• Other study ID #: RC22_0108
• Status: Recruiting
• Start date: November 22, 2022
• Est. completion date: January 2025

Study information

• Verified date: November 2022
• Source: Nantes University Hospital
• Contact: Karim Lakhal, MD
• Phone: 02 40 16 52 99
• Email: karim.lakhal[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The prediction and early detection of acute renal failure associated with cardiac surgery (ARF-CS) are desirable in order to try to reduce its magnitude. Indeed, its incidence is high (29 to 36%, reaching up to 81% in some series, depending on the vulnerability of the target population) and its consequences are often serious: prolongation of the length of stay in the intensive care unit and in hospital, death, and evolution towards chronic renal failure, possibly end-stage (justifying long-term extra-renal purification and/or renal transplantation). The challenge is all the more crucial given the high volume of cardiac surgery. In this context, the objective of identifying early on patients at high risk of developing AKI-CC - and therefore eligible for "nephroprotective" measures has generated, in the last decade, a strong interrest around preoperative scores and biomarkers. Thus, more than ten models predicting AKI-CC have been developed and more than 150 candidate biomarkers have been identified since 2004. This insterest is not waning. The DETECT-AKI project aims to evaluate, in a large population (N=400 patients) with varied patient profiles, not only the performance of the most innovative and promising preoperative scores and biomarkers described in the literature, but also the combination of biomarkers with relevant perioperative clinical and biological data in the framework of a clinico-biological score for the early identification of AKI-CC

Description:

The DETECT-AKI study aims at establishing an innovative composite score, the basis for decision making in the early initiation of nephroprotection measures. This score will include early clinical and biological data before, during and after surgery and may therefore include one or more modern biomarkers. The DETECT-AKI study foresees from the outset the internal validation of the score by bootstrap method: first essential step for the subsequent application of the established score. This is also one of the strengths of the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: January 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults undergoing scheduled, combined, cardiac surgery with CEC.

• "Combined" cardiac surgery (as opposed to simple cardiac surgery, which is less likely to result in ARF-CC) involves:

• 2 heart valves (and possibly other procedures) or =2 types of procedures among coronary artery bypass graft(s), valve, myocardial, and thoracic aortic surgery.

• A "scheduled" surgical procedure implies that the patient was added to the operative schedule more than 24 hours before the procedure.

Exclusion Criteria:

• unscheduled cardiac surgery

• at least one session of extra-renal purification in the week prior to surgery

• Patient refusal to participate in this research,

• participation in a study with a possible impact on the incidence of AKI-CC

• pregnant woman

• minor, adult under guardianship, protected person.

• no biomarker concentrations were measured and no clinico-biological scores were determined,

• no pre-CEC creatinine assay is available,

• the patient dies before H48 unless AKI-CC has occurred in the interim,

• the patient withdraws consent to participate in the study.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Renal Insufficiency

Intervention

Diagnostic Test:
• Early biomarkers of acute kidney injury
The biomarkers tested will be: creatinine levels [pre-, post-CC, H6], urinary TIMP2*IGFBP7 [H6], Plasma NGAL [Pre-, Post-CC, H6]. Urinary NGAL [H6] Plasma cystatin C [Pre-CC, Post-CEC & H6], plasma HI [pre-, post-CC, H6], plasma IL-6 [post-CC, H6], uremia [pre-, post-CC, H6], urinary DKK3 [pre-CC], These biomarkers will, if necessary, be corrected for hemodilution or dilution of urine, if any, using [pre-, post-CC, H6] protein and [pre-, post-CC, H6] creatinine, respectively.

Locations

Country	Name	City	State
France	Nantes UH	Nantes

Sponsors (5)

Lead Sponsor	Collaborator
Nantes University Hospital	BiologBook, BioMérieux, Roche Pharma AG, ThermoFisher Scientific Brahms Biomarkers France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	composite score	The primary endpoint will be ASCroc associated with the DETECT-AKI composite score established at H6.; AKI-CC will be based on the current international definition (elevation of creatinine and/or occurrence of oliguria within 48 h postoperatively). Internal validation of the score will be based on a bootstrap resampling method.	From pre-CC to 6th hour post CC
Secondary	Early renal biomarkers performance (creatininemia, urinary TIMP*IGFBP7, plasma and urinary NGAL, plasma Cystatin C / Plasma Hemolysis Index (PH) / interleukin-6, uremia and urinary DKK3)	Comparison of individual biomarker performance in identifying AKI-CC (all stages) at or before the 6th hour post-CC. The performance of an isolated measurement (at a given perioperative time) of a given biomarker will be analyzed, as well as the variation over time of the concentration of this biomarker (diagnostic performance of the biomarker kinetics).	From pre-CC to 6th hour post CC
Secondary	Score performance of early renal biomarkers (creatininemia, urinary TIMP*IGFBP7, plasma and urinary NGAL, plam Cystatin C, IH, IL6, uremia and urinary DKK3)	Comparison of the performance of scores proposed in the literature for the prediction of AKI-CC (all stages) on pre-operative data: Cleveland Clinic Foundation score (dialysis risk for severe AKI (grade III) after cardiac surgery from 0 to 13 (highest risk); Mehta score (calculator that estimates the risk of dialysis after cardiac surgery on demographic and antecedent data for severe AKI (grade III); Ng score (same as Metha score without endocarditis data); Simplified Predictive Index (for renal replacement therapy (RRT) after cardiac surgery from 0 to 8 (highest risk); Leicester score (predicts CSA-AKI of any stage after cardiac surgery using a formula taking into account KDIGO stage but without diuresis); EuroSCORE II (calculator that estimates the risk of dialysis after cardiac surgery on demographic, antecedent data using a formula)	From pre-CC to 6th hour post CC
Secondary	Score and biomarkers performance for prediction	Comparison of the individual performances of scores and biomarkers for the prediction or early detection of moderate to severe AKI-CC (KDIGO stages II and III), rather than AKI-CC of any stage.	From pre-CC to 6th hour post CC
Secondary	Algorithm	Construction of a triage algorithm for early classification of patients according to risk of developing AKI-CC (any stage) with pre-operative data as well as per-operative and early post-operative data	From pre-CC to 6th hour post CC
Secondary	Biomarkers performance in AKI persistance (creatininemia, urinary TIMP*IGFBP7, plasma and urinary NGAL, plasma Cystatin C / Plasma Hemolysis Index (PH) / interleukin-6, uremia and urinary DKK3)	Evaluation of the performance of biomarkers to predict the transient or persistent nature of AKI-CC beyond the 48th hour in patients who have developed AKI-CC.	beyond 48th hour post CC to 7 days
Secondary	Sensitivity analysis	Sensitivity analysis: analysis of the performance of the composite score using; the strict KDIGO definition of AKI-CC, i.e. setting the observation time for the criterion "relative rise in creatinine" at 7 days.; omitting the diuresis criterion from the definition, as diuresis is sometimes considered misleading in the context of cardiac surgery (due to the frequent use of diuretics, for example).	At 7th days