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

Primary Purpose

Extracorporeal Circulation; Complications, Renal Failure, Circulation Disorder

Status
Recruiting
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
High CPB flow
Sponsored by
Sahlgrenska University Hospital, Sweden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Extracorporeal Circulation; Complications focused on measuring renal oxygenation, renal blood flow, cardiopulmonary bypass, tubular cell injury, N-acetyl-beta-D-glucosaminidase, nephrocheck, inflammation, hemolysis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Lukas LannemyrRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Normal CPB flow

High CPB flow

Arm Description

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

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

Outcomes

Primary Outcome Measures

Biomarker u-NAG
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
Renal biomarker assay Nephrocheck (IGFBP-7 x TIMP-2) will be analyzed in urine
Renal oxygen delivery and blood flow
Renal oxygen delivery during and after cardiopulmonary bypass (CPB)

Secondary Outcome Measures

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

Full Information

First Posted
February 4, 2019
Last Updated
May 4, 2022
Sponsor
Sahlgrenska University Hospital, Sweden
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1. Study Identification

Unique Protocol Identification Number
NCT04084301
Brief Title
Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation, Blood Flow and Tubular Injury
Acronym
ICAROX2
Official Title
Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation, Blood Flow and Tubular Injury
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sahlgrenska University Hospital, Sweden

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extracorporeal Circulation; Complications, Renal Failure, Circulation Disorder, Renal Plasma Flow, Effective, Cardiopulmonary Bypass, Hemolysis, Inflammatory Response
Keywords
renal oxygenation, renal blood flow, cardiopulmonary bypass, tubular cell injury, N-acetyl-beta-D-glucosaminidase, nephrocheck, inflammation, hemolysis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
To compare normal (2.4 L/min/m2) and high (2.9 L/min/m2) cardiopulmonary bypass flow during cardiac surgery
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Normal CPB flow
Arm Type
No Intervention
Arm Description
In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.4 L/min/m2 throughout the CPB period.
Arm Title
High CPB flow
Arm Type
Experimental
Arm Description
In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.9 L/min/m2 throughout the CPB period.
Intervention Type
Procedure
Intervention Name(s)
High CPB flow
Intervention Description
Target CPB flow 2.9 L/min/m2 throughout the CPB period
Primary Outcome Measure Information:
Title
Biomarker u-NAG
Description
Tubulus injury biomarker N-acetyl-ß-d-glucoseaminidase (NAG) will be analyzed in urine with a spectrophotometric method and corrected for urine creatinine.
Time Frame
24 hours
Title
Biomarkers Nephrocheck
Description
Renal biomarker assay Nephrocheck (IGFBP-7 x TIMP-2) will be analyzed in urine
Time Frame
24 hours
Title
Renal oxygen delivery and blood flow
Description
Renal oxygen delivery during and after cardiopulmonary bypass (CPB)
Time Frame
6 hours
Secondary Outcome Measure Information:
Title
Serum creatinine and acute kidney injury (AKI)
Description
Changes in serum creatinine
Time Frame
48 hours
Title
Inflammation IL-1
Description
Differences in inflammatory marker IL-1
Time Frame
24 hours
Title
Inflammation IL-6
Description
Differences in inflammatory marker IL-6
Time Frame
24 hours
Title
Inflammation IL-8
Description
Differences in inflammatory marker IL-8
Time Frame
24 hours
Title
Inflammation IL-10
Description
Differences in inflammatory markers IL-1, IL-6, IL-8, IL-10 and TNFa
Time Frame
24 hours
Title
Inflammation TNFa
Description
Differences in inflammatory marker TNFa
Time Frame
24 hours
Title
Complement activation
Description
Differences in complement activation
Time Frame
24 hours
Title
Hemolysis
Description
Differences in markers of hemolysis (free plasma Hb, LD, haptoglobin)
Time Frame
24 hours
Title
Erythropoetin
Description
Differences in serum-erythropoietin
Time Frame
24 hours
Title
Neuroinflammation Tau
Description
Changes in Tau
Time Frame
4 days
Title
Neuroinflammation NF
Description
Changes Neurofilament
Time Frame
4 days
Title
Kidney function
Description
Measured glomerular filtration rate (iohexol clearance) on postoperative day 1
Time Frame
24 hours
Title
Renal function
Description
Measured glomerular filtration rate by iohexole clearance on the first postoperative day
Time Frame
24 hours
Other Pre-specified Outcome Measures:
Title
Urinary pO2
Description
Changes in urinary pO2 measured with laser doppler technique. Correlation with global renal oxygenation will be explored.
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lukas Lannemyr, MD
Phone
+46313428860
Email
lukas.lannemyr@vgregion.se
First Name & Middle Initial & Last Name or Official Title & Degree
Sven-Erik Ricksten, MD, PhD
Phone
+46313421000
Ext
7433
Email
sven-erik.ricksten@aniv.gu.se
Facility Information:
Facility Name
Lukas Lannemyr
City
Göteborg
State/Province
Västra Götaland
ZIP/Postal Code
416 53
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lukas Lannemyr, MD, PhD
Phone
+46313428860
Email
lukas.lannemyr@vgregion.se
First Name & Middle Initial & Last Name & Degree
Sven-Erik Ricksten, MD, PhD
Email
sven-erik.ricksten@aniv.gu.se
First Name & Middle Initial & Last Name & Degree
Johanna Wijk, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27906706
Citation
Lannemyr L, Bragadottir G, Krumbholz V, Redfors B, Sellgren J, Ricksten SE. Effects of Cardiopulmonary Bypass on Renal Perfusion, Filtration, and Oxygenation in Patients Undergoing Cardiac Surgery. Anesthesiology. 2017 Feb;126(2):205-213. doi: 10.1097/ALN.0000000000001461.
Results Reference
background
PubMed Identifier
30365961
Citation
Lannemyr L, Bragadottir G, Hjarpe A, Redfors B, Ricksten SE. Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation in Patients Undergoing Cardiac Operations. Ann Thorac Surg. 2019 Feb;107(2):505-511. doi: 10.1016/j.athoracsur.2018.08.085. Epub 2018 Oct 23.
Results Reference
result
PubMed Identifier
28748536
Citation
Lannemyr L, Lundin E, Reinsfelt B, Bragadottir G, Redfors B, Oras J, Ricksten SE. Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N-acetyl-ss-D-glucosaminidase. Acta Anaesthesiol Scand. 2017 Oct;61(9):1075-1083. doi: 10.1111/aas.12946. Epub 2017 Jul 26.
Results Reference
result

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

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