Clinical trial NCT05189262: Cardiopulmonary Bypass Induced Red Blood Cell Lysis
Official title: Extra-Cellular Hemoglobin, Organ Injury in Extended Cardiopulmonary Bypass
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiopulmonary Bypass
Cardiac Surgery
Kidney Injury, Acute
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-01-12
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Research Participants will include approximately 90 adult (\>/=18 years of age to 75 years of age) medium to high risk patients. Both Male and female subjects who are undergoing complex cardiac surgery requiring, heart valve replacement, or CABG surgery requiring cardiopulmonary bypass \>1hr will be eligible for enrollment at the University of Maryland Medical Center (UMMC) in Baltimore, MD. This study is a prospective observational investigation.

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Admitted to UMMC for cardiac procedure
* Age: \>/=18 y.o TO 88 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

Primary outcomes:
measure: Hemolysis
timeFrame: Change from baseline at hour 1 during procedure
measure: Hemolysis
timeFrame: Change from baseline at hour 2 during procedure
measure: Hemolysis
timeFrame: Change from baseline at hour 3 during procedure
measure: Hemolysis
timeFrame: Change from baseline at hour 4 during procedure
measure: Hemolysis
timeFrame: Change from baseline at hour 4 post procedure
measure: Hemolysis
timeFrame: Change from baseline at hour 2 post procedure
measure: Hemolysis
timeFrame: Change from baseline at hour 24 post procedure
measure: Hemolysis
timeFrame: Change from baseline on day 2 post procedure
measure: Hemolysis
timeFrame: Change from baseline on day 3 post procedure
measure: Hemolysis
timeFrame: Change from baseline on day 4 post procedure
measure: Hemolysis
timeFrame: Change from baseline on day 5 post procedure
Secondary outcomes:
measure: Kidney injury
timeFrame: Change from baseline at hour 1 during procedure
measure: Kidney injury
timeFrame: Change from baseline at hour 2 during procedure
measure: Kidney injury
timeFrame: Change from baseline at hour 3 during procedure
measure: Kidney injury
timeFrame: Change from baseline at hour 4 during procedure
measure: Kidney injury
timeFrame: Change from baseline at hour 2 post procedure
measure: Kidney injury
timeFrame: Change from baseline at hour 24 post procedure
measure: Kidney injury
timeFrame: Change from baseline at 2 days post procedure
measure: Kidney injury
timeFrame: Change from baseline at 3 days post procedure
measure: Kidney injury
timeFrame: Change from baseline at 4 days post procedure
measure: Kidney injury
timeFrame: Change from baseline at 5 days post procedure
Other outcomes:
measure: Blood cell function
timeFrame: Change from baseline at hour 1 during procedure
measure: Blood cell function
timeFrame: Change from baseline at hour 2 during procedure
measure: Blood cell function
timeFrame: Change from baseline at hour 3 during procedure
measure: Blood cell function
timeFrame: Change from baseline at hour 4 during procedure
measure: Blood cell function
timeFrame: Change from baseline at hour 2 post procedure
measure: Blood cell function
timeFrame: Change from baseline at hour 24 post procedure
measure: Blood cell function
timeFrame: Change from baseline at day 2 post procedure
measure: Blood cell function
timeFrame: Change from baseline at day 3 post procedure
measure: Blood cell function
timeFrame: Change from baseline at day 4 post procedure
measure: Blood cell function
timeFrame: Change from baseline at day 5 post procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at hour 1 during procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at hour 2 during procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at hour 3 during procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at hour 4 during procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at hour 2 post procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at hour 24 post procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at day 2 post procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at day 3 post procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at day 4 post procedure
measure: Outcome Hemoglobin Clearance
timeFrame: Change from baseline at day 5 post procedure
Locations:
city: Baltimore
country: United States
facility: Center for Blood Oxygen Transport and Hemostasis
state: Maryland
Study officials:
affiliation: University of Maryland
name: Paul Buehler, PhD
role: PRINCIPAL_INVESTIGATOR
References: