Optimizing Pulsatility During Cardiopulmonary Bypass to Reduce Acute Kidney Injury

Optimizing Pulsatility During Cardiopulmonary Bypass to Reduce Acute Kidney Injury: Randomized Controlled Trial

The objective is to determine the effectiveness of pulsatile flow during cardiopulmonary bypass to reduce the incidence of acute kidney injury after cardiac surgery. Investigators will also evaluate the safety and impact of pulsatile flow on clinical outcomes compared to non-pulsatile flow during cardiopulmonary bypass.

Study Overview

• Status: Recruiting
• Conditions: Thrombocytopenia; Surgery; Acute Kidney Injury; Hemolysis
• Intervention / Treatment: Other: Non-pulsatile blood flow; Other: Pulsatile blood flow

Detailed Description

Non-pulsatile and pulsatile blood flow during cardiopulmonary bypass for cardiac surgery are both considered standard of care and allow surgeons to operate on the heart without movement. Pulsatile cardiopulmonary bypass produces variations in blood flow to produce a pulse similar to a normal beating heart. Non-pulsatile and pulsatile blood flow during cardiopulmonary bypass are approved as safe and effective ways to provide perfusion during cardiac surgery, but it is unknown whether there are differences in clinical outcomes after surgery. Acute kidney injury is common after cardiac surgery and may be caused by inadequate perfusion during cardiopulmonary bypass.

Specific Aim: The purpose of this study is to determine the effectiveness of pulsatile blood flow during cardiopulmonary bypass to reduce the incidence of acute kidney injury after cardiac surgery compared to non-pulsatile blood flow.

Hypothesis: Pulsatile blood flow during cardiopulmonary bypass will reduce the incidence of acute kidney injury after cardiac surgery compared to non-pulsatile blood flow.

• Study Type: Interventional
• Enrollment (Estimated): 1100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathan J Clendenen, MD,MS; Phone Number: 3037245000; Email: nathan.clendenen@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital
      • Principal Investigator: Nathan J Clendenen, MD MS
      • Contact: Nathan Clendenen, MD MS; Email: nathan.clendenen@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to provide informed consent
• Scheduled for elective cardiac surgery with cardiopulmonary bypass

Exclusion Criteria

• Emergency procedures
• Scheduled for heart or lung transplantation
• Scheduled for ventricular assist device implantation
• Use of the Medtronic Elongated Once-Piece Arterial Cannula
• Diagnosed with sepsis
• Diagnosed with delirium
• Experiencing hemodynamic instability (heart rate > 100 and systolic blood pressure < 90)
• Requiring mechanical circulatory support
• Requiring vasoactive medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non-pulsatile blood flow; Non-pulsatile blood flow during cardiopulmonary bypass	Other: Non-pulsatile blood flow; Non-pulsatile blood flow generated by constant centrifugal pump flow rate during cardiopulmonary bypass
Active Comparator: Pulsatile blood flow; Pulsatile blood flow during cardiopulmonary bypass	Other: Pulsatile blood flow; Pulsatile blood flow generated by variable centrifugal pump flow rate during cardiopulmonary bypass

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	Stage 1 (mild), 2 (moderate), or 3 (severe) acute kidney injury according to the Kidney Disease Improving Global Outcomes creatinine criteria (stage 1 = 1.5 to 1.9 times baseline or greater than or equal to 0.3 milligrams per deciliter increase in serum creatinine, stage 2 = 2.0 to 2.9 times baseline in serum creatinine, stage 3 = 3.0 times baseline or increase in serum creatinine greater than or equal to 4.0 milligrams per deciliter or initiation of renal replacement therapy	From intensive care unit admission after surgery up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury risk score	Demirjian Perioperative Laboratory Test-Based Prediction Model for Moderate to Severe Acute Kidney Injury After Cardiac Surgery in percent predicted risk	On admission to the intensive care unit after surgery up to 24 hours after intensive care unit arrival
Red blood cell units transfused	Number of allogenic red blood cell units transfused after cardiopulmonary bypass	After cardiopulmonary bypass up to 24 hours after intensive care unit arrival
Platelet nadir	Lowest platelet count after cardiopulmonary bypass	On admission to the intensive care unit after surgery up to 7 days
Discontinuation rate of cardiopulmonary bypass mode	Discontinuation rate of pulsatile or non-pulsatile cardiopulmonary bypass mode	During cardiopulmonary bypass
30-day mortality	All cause mortality	From intensive care unit admission after surgery to hospital discharge, up to 30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
New onset of left ventricular systolic dysfunction	New onset of left ventricular systolic dysfunction determined by a LV ejection fraction <50%	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New onset of right ventricular systolic dysfunction	New onset of right ventricular systolic dysfunction determined by a tricuspid annular plane systolic excursion less than 16 mm	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Myocardial infarction	Myocardial infarction by clinical diagnosis	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Stroke	Stroke by clinical diagnosis	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Renal failure requiring renal replacement therapy	New diagnosis of renal failure requiring renal replacement therapy	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Re-exploration for bleeding	Surgical re-exploration for bleeding	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Sepsis	Diagnosed by positive blood culture	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New onset atrial fibrillation	Clinical diagnosis of new onset atrial fibrillation	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Duration of mechanical ventilation	Duration of mechanical ventilation	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative delirium	Post-operative determined by the Confusion Assessment Method for the Intensive Care Unit	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative hospital length of stay	Post-operative hospital length of stay	From intensive care unit admission after surgery to hospital discharge, up to 30 days
New requirement for mechanical circulatory support	New requirement for mechanical circulatory support	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Intra-operative red blood cell transfusion in units	Intra-operative red blood cell transfusion in units	During the intra-operative time period, up to 12 hours
Post-operative red blood cell transfusion in units	Post-operative red blood cell transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative platelet transfusion in units	Post-operative platelet transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative plasma transfusion in units	Post-operative plasma transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Post-operative cryoprecipitate transfusion in units	Post-operative cryoprecipitate transfusion in units	From intensive care unit admission after surgery to hospital discharge, up to 30 days
Intra-operative platelet transfusion in units	Intra-operative platelet transfusion in units	During the intra-operative time period, up to 12 hours
Intra-operative plasma transfusion in units	Intra-operative plasma transfusion in units	During the intra-operative time period, up to 12 hours
Intra-operative cryoprecipitate transfusion in units	Intra-operative cryoprecipitate transfusion in units	During the intra-operative time period, up to 12 hours
New onset of acute lung injury	Diagnosis of acute lung injury by PaO2 to FiO2 ratio ≤ 300	From intensive care unit admission after surgery to hospital discharge, up to 30 days

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Nathan J Clendenen, MD, MS, University of Colorado, Denver

Publications and helpful links

General Publications

• Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. No abstract available.
• Demirjian S, Bashour CA, Shaw A, Schold JD, Simon J, Anthony D, Soltesz E, Gadegbeku CA. Predictive Accuracy of a Perioperative Laboratory Test-Based Prediction Model for Moderate to Severe Acute Kidney Injury After Cardiac Surgery. JAMA. 2022 Mar 8;327(10):956-964. doi: 10.1001/jama.2022.1751.
• Tan A, Newey C, Falter F. Pulsatile Perfusion during Cardiopulmonary Bypass: A Literature Review. J Extra Corpor Technol. 2022 Mar;54(1):50-60. doi: 10.1182/ject-50-60.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 4, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Cytopenia; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Hematologic Diseases; Renal Insufficiency; Blood Platelet Disorders; Acute Kidney Injury; Wounds and Injuries; Thrombocytopenia; Hemolysis
• Other Study ID Numbers: 23-0921; 5K23HL151882 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No