Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial.

BACKGROUND

When safe to do so, avoiding blood transfusions in cardiac surgery can avoid the risk of transfusion-related infections and other complications while protecting a scarce resource and reducing costs. This protocol describes a kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS-III) trial, a multinational noninferiority randomized controlled trial to determine whether the risk of major clinical outcomes in patients undergoing planned cardiac surgery with cardiopulmonary bypass is no greater with a restrictive versus liberal approach to red blood cell transfusion.

OBJECTIVE

The objective of this substudy is to determine whether the risk of acute kidney injury is no greater with a restrictive versus liberal approach to red blood cell transfusion, and whether this holds true in patients with and without preexisting chronic kidney disease.

DESIGN AND SETTING

Multinational noninferiority randomized controlled trial conducted in 73 centers in 19 countries (2014-2017).

PATIENTS

Patients (~4800) undergoing planned cardiac surgery with cardiopulmonary bypass.

MEASUREMENTS

The primary outcome of this substudy is perioperative acute kidney injury, defined as an acute rise in serum creatinine from the preoperative value (obtained in the 30-day period before surgery), where an acute rise is defined as ≥26.5 μmol/L in the first 48 hours after surgery or ≥50% in the first 7 days after surgery.

METHODS

We will report the absolute risk difference in acute kidney injury and the 95% confidence interval. We will repeat the primary analysis using alternative definitions of acute kidney injury, including staging definitions, and will examine effect modification by preexisting chronic kidney disease (defined as a preoperative estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m).

LIMITATIONS

It is not possible to blind patients or providers to the intervention; however, objective measures will be used to assess outcomes, and outcome assessors will be blinded to the intervention assignment.

RESULTS

Substudy results will be reported by the year 2018.

CONCLUSIONS

This substudy will provide generalizable estimates of the risk of acute kidney injury of a restrictive versus liberal approach to red blood cell transfusion in the presence of anemia during cardiac surgery done with cardiopulmonary bypass.

TRIAL REGISTRATION

www.clinicaltrials.gov; clinical trial registration number NCT 02042898.