Acute Kidney Injury After Cardiac Surgery

Study Overview
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Brief Summary
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PrimECC is a colloid priming solution for cardiopulmonary bypass/ extracorporeal circulation (ECC) based on Ringers Lactate, supplmeneted with Dextran 40 and Dextran 1. In a previous RCT comparing PrimECC with crystalloid priming fluid, patients in the PrimECC group experienced less hemolysis, less tubular cell injury and beneficial effect on the fluid balance. This study will investigate if, in a population at high risk of acute kidney injury (AKI), priming the ECC circuit with PrimECC instead of crystalloid solution will lead to a reduction of postoperative AKI. The hypothesis is that PrimECC, compared to crystalloid prime, will reduce postoperative AKI. The study is a Swedish multicenter, double-blinded, randomized, controlled clinical trial. The trial will include 366 patients aged ≥18 years, scheduled for cardiac surgery with cardiopulmonary bypass, with an Acute kidney injury risk score ≥30% according to Birnie et al. (2014). The primary outcome of the study is the incidence of postoperative AKI of any stage according to the KDIGO creatinine criteria (serum-creatinine increase ≥ 27 μmol/l within 48 h or ≥ 50 % increase from baseline) within 96 hours after arrival to the ICU. Secondary outcomes are between-group differences in hemolysis, tubular cell injury (NAG-excretion), estimated GFR, and incidence of AKI of different stages according to the KDIGO creatinine criteria. In addition, differences in CNS (Tau, NFL, NSE, and S100B) and cardiac (TNT/TNI) injury markers will be investigated.

Official Title
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Acute Kidney Injury After Cardiac Surgery; A Prospective Randomized Study of Dextran Based and Crystalloid Priming Solutions (PRIMING II Trial)

Conditions
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Cardiac Surgical Procedures, Extracorporeal Circulation; Complications, Acute Kidney Injury

Intervention / Treatment
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* Device: Colloid priming solution for ECC circuit
* Device: Standard priming solution for ECC circuit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed and dated the EC approved informed consent Subject is ≥ 18 years of age Requires elective or urgent (non-emergency) cardiac procedure requiring the use of ECC. Preoperative Acute kidney injury risk score ≥30%, found at http://cardiacsurgeryleicester.com/our-research/acute-kidney-injury-risk-score-calculator/ Exclusion Criteria: Unable to give informed consent Known bleeding disorder Known intolerance or contraindication to dextran Acute Surgery (requires emergency cardiac procedure/surgery) Currently using an antithrombotic medication which has not been discontinued per institution protocol Malignancy; Surgery within 5 years or ongoing antitumoral treatment Has ongoing sepsis or endocarditis Requires pre-operative dialysis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colloid priming solution for ECC circuit<br>Priming of ECC circuit with approximately 1200 mL PrimECC. | Device: Colloid priming solution for ECC circuit<br>* Prospective, multi-center, double-blinded, randomized, controlled clinical trial<br>|
| Active Comparator: Standard priming solution for ECC circuit<br>Priming of ECC circuit with approximately 1200 mL standard priming solution (crystalloid solution with or without mannitol addition as per routine of the participating clinic). | Device: Standard priming solution for ECC circuit<br>* Prospective, multi-center, double-blinded, randomized, controlled clinical trial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of post-operative AKI | Incidence of postoperative AKI of any stage according to the KDIGO creatinine criteria (serum-creatinine increase ≥ 27 μmol/l within 48 hours or ≥ 50 % increase from baseline) | Within 96 hours after ICU arrival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NAG excretion | NAG-excretion (U-NAG/U-creatinine) | 1 hour post initiation of ECC, at 1 hour after disconnection from ECC and 24 hours after disconnection from ECC. | 
| eGFR | pre-operative (day before surgery) compared to the highest post-operative value Measured value of pre-operative eGFR compared to the highest post-operative value within 96 hours after ICU arrival, calculated using the CKD-EPI formula | Pre-operative and within 96 hours after ICU arrival | 
| Incidence of AKI | Incidence of AKI of different stages according to the KDIGO creatinine criteria | Within 96 hours after ICU arrival | 
| Hemolysis | Hemolysis measured as free hemoglobin (PfHb) | Pre-operative (after induction of anesthesia) and at 1 hour post initiation of ECC, 1 hour after disconnection from ECC and at 24 hours after disconnection from ECC. | 
| CNS injury markers | Measured concentrations of CNS injury markers Tau, NFL, NSE, and S100B | Pre-operative (after induction of anesthesia), 1 hour after disconnection from ECC and at 24 hours after disconnection from ECC. | 
| Myocardial injury markers | Measured concentrations of myocardial injury markers TnI or TnT. TnI or TnT is chosen according to institutional standard | Pre-operative (after induction of anesthesia) and at 1 hour after discontinuation of ECC and 24 hours after disconnection from ECC. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colloid priming solution, Cardiopulmonary bypass, Extracorporeal circulation, ECC, Acute Kidney Injury, AKI