Cardiopulmonary Bypass Induced Red Blood Cell Lysis

Cardiac Surgery Clinical Trial

Official title:

Extra-Cellular Hemoglobin, Organ Injury in Extended Cardiopulmonary Bypass

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05189262
• Other study ID #: HP-00094849
• Secondary ID: 1R01HL162120-01
• Status: Recruiting
• Start date: March 22, 2022
• Est. completion date: January 1, 2026

Study information

• Verified date: November 2023
• Source: University of Maryland, Baltimore
• Contact: Paul W Buehler, PhD
• Phone: 14107065171
• Email: pbuehler[@]som.umaryland.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury, limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB.

Description:

Cost estimates for brain, lung, cardiac, and kidney complications following complex cardiac surgeries that require a medical assist device to by-pass the heart and lungs (cardiopulmonary bypass, CPB) is estimated to cost $80 million per individual states in the US over a ten-year period. These extra costs represent a significant burden on the healthcare system but could be reduced by understanding how medical assist devices lead to organ injury associated with complex cardiac surgeries. The primary goals of this research are to (1) understand how hemoglobin released into plasma (pfH) from damaged red blood cells that passage through CPB contributes to organ injury. (2) Determine the amount of pfH necessary to cause organ injury. (3) Determine the concentration changes in protective proteins (called haptoglobin, hemopexin and transferrin) that remove pfH and its degradation products from the circulation. (4) Design a computer-based model that will determine the levels of pfH and protective proteins to predict the potential for organ injury. By studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB. The primary goals of this research are to (1) understand how hemoglobin released into plasma (pfH) from damaged red blood cells that passage through CPB contributes to organ injury. (2) Determine the amount of pfH necessary to cause organ injury. (3) Determine the concentration changes in protective proteins (called haptoglobin, hemopexin and transferrin) that remove pfH and its degradation products from the circulation. (4) Design a computer-based model that will determine the levels of pfH and protective proteins to predict the potential for organ injury. By studying the dynamics of red blood cell lysis, pfH, protective proteins and organ injury limits will be set for safe levels of pfH following the use of CPB. These results will be compared to existing laboratory-based methods for determining red blood cell damage to predict CPB assist device safety. Further, results from the studies described in this proposal will help develop therapeutic strategies to benefit patients by early detection of pfH and clearance protein levels that occur during CPB.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 1, 2026
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Admitted to UMMC for cardiac procedure

• Age: >/=18 y.o TO 75 y.o.

• Undergoing CPB >1hr for the following surgeries (a) complex cardiac surgery (b) heart valve replacement surgery OR (c) CABG surgery.

Exclusion Criteria:

• Pregnant

• Non English speaking

• Unable to consent or have Legally Authorized Representative (LAR) assent to study

Related Conditions & MeSH terms

• Acute Kidney Injury
• Cardiac Surgery
• Cardiopulmonary Bypass
• Kidney Injury, Acute

Intervention

Other:
• Blood and urine collection
No intervention - Biological specimen collection

Locations

Country	Name	City	State
United States	Center for Blood Oxygen Transport and Hemostasis	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 1 during procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 2 during procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 3 during procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 4 during procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 2 post procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at hour 24 post procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at day 2 post procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at day 3 post procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at day 4 post procedure
Other	Blood cell function	CBC and red blood cell deformability	Change from baseline at day 5 post procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 1 during procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 2 during procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 3 during procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 4 during procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 2 post procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at hour 24 post procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 2 post procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 3 post procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 4 post procedure
Other	Outcome Hemoglobin Clearance	Change in hemoglobin clearance measured by plasma haptoglobin and transferrin concentrations	Change from baseline at day 5 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron	Change from baseline at hour 1 during procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron	Change from baseline at hour 2 during procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron	Change from baseline at hour 3 during procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline at hour 4 during procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline at hour 4 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline at hour 2 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline at hour 24 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline on day 2 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline on day 3 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline on day 4 post procedure
Primary	Hemolysis	Change in Measure hemoglobin released into plasma (pfH), lactate dehydrogenase and iron etc.; Change from Baseline at Hour 1 during procedure	Change from baseline on day 5 post procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 1 during procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 2 during procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 3 during procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 4 during procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 2 post procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at hour 24 post procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 2 days post procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 3 days post procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 4 days post procedure
Secondary	Kidney injury	Change in creatinine, KIM-1 and NGAL	Change from baseline at 5 days post procedure