ICAROX2: Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation, Blood Flow and Tubular Injury

Sponsor

Sahlgrenska University Hospital, Sweden (Other)

Overall Status

Recruiting

CT.gov ID

NCT04084301

Collaborator

(none)

100

Enrollment

Location

Arms

51.1

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

During open cardiac surgery, cardiopulmonary bypass (CPB) is used to temporarily replace the function of the heart and lungs. Renal ischemia resulting in acute kidney injury is common after cardiac surgery. The renal oxygenation is impaired during CPB, but the oxygenation may be improved by increasing the CPB blood flow. In this randomized study, two CPB flow rates will be compared regarding renal outcome (biomarkers and renal oxygenation/renal blood flow), as well as markers of inflammation and hemolysis. Additionally, urine oxygen tension will be measured during CPB and the early intensive care phase and compared to renal oxygenation. Regional oxygen saturation assessed with near infrared spectroscopy from the brain and kidneys will be monitored during and after surgery.

Condition or Disease	Intervention/Treatment	Phase
Extracorporeal Circulation; Complications Renal Failure Circulation Disorder Renal Plasma Flow, Effective Cardiopulmonary Bypass Hemolysis Inflammatory Response	Procedure: High CPB flow	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

To compare normal (2.4 L/min/m2) and high (2.9 L/min/m2) cardiopulmonary bypass flow during cardiac surgeryTo compare normal (2.4 L/min/m2) and high (2.9 L/min/m2) cardiopulmonary bypass flow during cardiac surgery

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation, Blood Flow and Tubular Injury

Actual Study Start Date :

Sep 27, 2019

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Normal CPB flow In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.4 L/min/m2 throughout the CPB period.
Experimental: High CPB flow In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.9 L/min/m2 throughout the CPB period.	Procedure: High CPB flow Target CPB flow 2.9 L/min/m2 throughout the CPB period

Arm

Intervention/Treatment

No Intervention: Normal CPB flow

In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.4 L/min/m2 throughout the CPB period.

Experimental: High CPB flow

In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.9 L/min/m2 throughout the CPB period.

Procedure: High CPB flow

Target CPB flow 2.9 L/min/m2 throughout the CPB period

Outcome Measures

Primary Outcome Measures

Biomarker u-NAG [24 hours]
Tubulus injury biomarker N-acetyl-ß-d-glucoseaminidase (NAG) will be analyzed in urine with a spectrophotometric method and corrected for urine creatinine.
Biomarkers Nephrocheck [24 hours]
Renal biomarker assay Nephrocheck (IGFBP-7 x TIMP-2) will be analyzed in urine
Renal oxygen delivery and blood flow [6 hours]
Renal oxygen delivery during and after cardiopulmonary bypass (CPB)

Secondary Outcome Measures

Serum creatinine and acute kidney injury (AKI) [48 hours]
Changes in serum creatinine
Inflammation IL-1 [24 hours]
Differences in inflammatory marker IL-1
Inflammation IL-6 [24 hours]
Differences in inflammatory marker IL-6
Inflammation IL-8 [24 hours]
Differences in inflammatory marker IL-8
Inflammation IL-10 [24 hours]
Differences in inflammatory markers IL-1, IL-6, IL-8, IL-10 and TNFa
Inflammation TNFa [24 hours]
Differences in inflammatory marker TNFa
Complement activation [24 hours]
Differences in complement activation
Hemolysis [24 hours]
Differences in markers of hemolysis (free plasma Hb, LD, haptoglobin)
Erythropoetin [24 hours]
Differences in serum-erythropoietin
Neuroinflammation Tau [4 days]
Changes in Tau
Neuroinflammation NF [4 days]
Changes Neurofilament
Kidney function [24 hours]
Measured glomerular filtration rate (iohexol clearance) on postoperative day 1
Renal function [24 hours]
Measured glomerular filtration rate by iohexole clearance on the first postoperative day

Other Outcome Measures

Urinary pO2 [24 hours]
Changes in urinary pO2 measured with laser doppler technique. Correlation with global renal oxygenation will be explored.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written, signed informed consent
Male and female subjects ≥18 years
Left ventricular ejection fraction ≥30 %
Estimated GFR ≥30 ml/min using the CKD-EPI equation (Levey 2009)
Scheduled open cardiac surgery with CPB
Planned normothermia during CPB
Expected CPB time > 60 minutes

Exclusion Criteria:

Emergency surgery
Cardiac transplantation
Advanced grown-up congenital heart disease corrections
Previous cerebral infarction, verified with computed tomography or magnetic resonance imaging
Body mass index > 32 kg/m2
Use of hypothermia < 32 °C during CPB
Inability of the patient to give based opinion
In the investigator´s opinion, the patient has a condition that could be adversely affected by study participation