CytoSorb® Reduction of FREee Hemoglobin/Acute Kidney Injury (AKI) During Cardiac Surgery (REFRESH II-AKI)

CytoSorb® Reduction of FREee Hemoglobin/Acute Kidney Injury (AKI) During Cardiac Surgery (REFRESH II Trial)

Prospective, multi-center, randomized, blinded, pivotal clinical study. Subjects will be randomized in a 1:1 ratio to either standard of care (SOC) alone or standard of care plus treatment with the CytoSorb® device.

Study Overview

• Status: Terminated
• Conditions: Elective Cardiac Surgery
• Intervention / Treatment: Device: CytoSorb

Detailed Description

To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI) as defined by Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline definition of acute kidney injury when used intraoperatively with cardiopulmonary bypass (CPB) in subjects undergoing cardiac surgery. The objective of using CytoSorb® treatment in this setting is to provide clinically meaningful improvements in renal function by mitigation of intraoperative injury by removal of nephrotoxic agents such as pfHb and complement. Up to 420 subjects will be enrolled and randomized at a 1:1 ratio at up to 40 investigational sites in the United States.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Methodist Hospital
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10075
      • Northwell Health: Lennox Hill Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital Linder Research Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Scheduled for non-emergent cardiac surgery requiring CPB for i) heart valve replacement with any other procedure, without hypothermic circulatory arrest (HCA), or ii) aortic reconstruction with or without another procedure, with HCA

Exclusion Criteria:

• Isolated Coronary Artery Bypass Graft
• Pregnant women
• Life expectancy of < 14 days
• End stage organ disease
• Active infection
• Correction of a congenital heart defect
• Contraindication to anticoagulation with heparin
• Minimally invasive surgery implantation (TAVI) or transcatheter aortic valve replacement (TAVR)
• Declined informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CytoSorb Device; Standard of care plus treatment with CytoSorb device installed on the Cardiopulmonary bypass (CPB) machine	Device: CytoSorb; To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI); Other Names: CytoSorb device used during cardiopulmonary bypass (CPB)
Placebo Comparator: Control; Standard of care	Device: CytoSorb; To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI); Other Names: CytoSorb device used during cardiopulmonary bypass (CPB)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB)	Incidence and severity of AKI in the first 48 hours after CPB, evaluated based on creatinine levels at CPB, 24 & 48h after CPB and urine output up to 48h.	From start of CPB through 48 hours after CPB

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Health Resource Utilization: ICU Duration (Hours)	Analysis of health resource utilization included parameters such as length of stay in ICU and hospital and need for supportive care measures such as vasopressors, and mechanical ventilation.	From start of CPB through discharge, average of 8.9 days.
Summary of Health Resource Utilization: Post-Op Hospital Stay: Date of Discharge - Date of ICU Admission	Analysis of health resource utilization included parameters such as length of stay in ICU and hospital and need for supportive care measures such as vasopressors, and mechanical ventilation.	From start of CPB through discharge, average of 8.9 days.
Summary of Health Resource Utilization: Number of Patients on Vasopressor Medication	Analysis of health resource utilization included parameters such as length of stay in ICU and hospital and need for supportive care measures such as vasopressors, and mechanical ventilation.	From start of CPB through discharge, average of 8.9 days.
Summary of Health Resource Utilization: Duration of Continuous Intra-op to Post-op Ventilator/ Mechanical Support Use	Analysis of health resource utilization included parameters such as length of stay in ICU and hospital and need for supportive care measures such as vasopressors, and mechanical ventilation.	From start of CPB through discharge, average of 8.9 days.
Initiation of Renal Replacement Therapy	Initiation of Renal Replacement Therapy up to 48 Hours post CPB	Up to 48 hours after CPB

Collaborators and Investigators

• Sponsor: CytoSorbents, Inc
• Investigators: Principal Investigator: Thomas Gleason, MD, not applicable- Unaffiliated with CytoSorbents

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2018
• Primary Completion (Actual): January 18, 2022
• Study Completion (Actual): January 18, 2022

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 28, 2017

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: inflammation; cardiopulmonary bypass; Acute Kidney Injury; CytoSorb device; Plasma free hemoglobin; extracorporeal cardiopulmonary bypass
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 2017-001

Drug and device information, study documents

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