Elective Cardiac Surgery
Conditions
Keywords
CytoSorb device, Plasma free hemoglobin, inflammation, extracorporeal cardiopulmonary bypass, cardiopulmonary bypass, Acute Kidney Injury
Brief summary
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.
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.
Interventions
DEVICECytoSorb
To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI)
Sponsors
CytoSorbents, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | From start of CPB through 48 hours after 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Health Resource Utilization: ICU Duration (Hours) | From start of CPB through discharge, average of 8.9 days. | 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. |
| Summary of Health Resource Utilization: Post-Op Hospital Stay: Date of Discharge - Date of ICU Admission | From start of CPB through discharge, average of 8.9 days. | 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. |
| Summary of Health Resource Utilization: Number of Patients on Vasopressor Medication | From start of CPB through discharge, average of 8.9 days. | 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. |
| Summary of Health Resource Utilization: Duration of Continuous Intra-op to Post-op Ventilator/ Mechanical Support Use | From start of CPB through discharge, average of 8.9 days. | 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. |
| Initiation of Renal Replacement Therapy | Up to 48 hours after CPB | Initiation of Renal Replacement Therapy up to 48 Hours post CPB |
Countries
United States
Participant flow
Pre-assignment details
34 Subjects exited study post consent, but pre-procedure: 21 of these were screen failures (20 did not meet eligibility criteria, 1 was reported as Screen failure for reasons other than not meeting the eligibility criteria). 4 were withdrawn due to investigator decision. 2 withdrew consent. 7 exited due to other reasons.
Participants by arm
| Arm | Count |
|---|---|
| CytoSorb Device Standard of care plus treatment with CytoSorb device installed on the Cardiopulmonary bypass (CPB) machine
CytoSorb: To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI) | 56 |
| Control Standard of care
CytoSorb: To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI) | 60 |
| Roll In: CytoSorb Device Unblinded: Standard of care plus treatment with CytoSorb device installed on the Cardiopulmonary bypass (CPB) machine
CytoSorb: To evaluate the safety and performance of the CytoSorb® device to decrease the incidence or severity of acute kidney injury (AKI) | 36 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Reason not provided | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Control | Roll In: CytoSorb Device | CytoSorb Device | Total |
|---|---|---|---|---|
| Age, Continuous | 64.10 years STANDARD_DEVIATION 11.88 | 66.14 years STANDARD_DEVIATION 11.84 | 66.98 years STANDARD_DEVIATION 11.87 | 65.64 years STANDARD_DEVIATION 11.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 32 Participants | 53 Participants | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 56 Participants | 31 Participants | 51 Participants | 138 Participants |
| Region of Enrollment United States | 60 participants | 36 participants | 56 participants | 152 participants |
| Sex: Female, Male Female | 18 Participants | 9 Participants | 18 Participants | 45 Participants |
| Sex: Female, Male Male | 42 Participants | 27 Participants | 38 Participants | 107 Participants |
| Smoking History Current Smoker | 2 participants | 3 participants | 10 participants | 15 participants |
| Smoking History Former Smoker | 28 participants | 16 participants | 19 participants | 63 participants |
| Smoking History Never Smoked | 30 participants | 17 participants | 27 participants | 74 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 56 | 1 / 60 | 0 / 36 |
| other Total, other adverse events | 35 / 56 | 44 / 60 | 30 / 36 |
| serious Total, serious adverse events | 28 / 56 | 21 / 60 | 14 / 36 |
Outcome results
Primary
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.
Time frame: From start of CPB through 48 hours after CPB
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 0 | 9 Participants |
| CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 1 (Mild) | 7 Participants |
| CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 2 (moderate) | 31 Participants |
| CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 3 (Severe) | 9 Participants |
| Control | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 3 (Severe) | 15 Participants |
| Control | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 0 | 12 Participants |
| Control | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 2 (moderate) | 28 Participants |
| Control | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 1 (Mild) | 5 Participants |
| Roll In: CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 3 (Severe) | 6 Participants |
| Roll In: CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 1 (Mild) | 2 Participants |
| Roll In: CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 2 (moderate) | 21 Participants |
| Roll In: CytoSorb Device | Incidence and Severity of Acute Kidney Injury (AKI) in the First 48 Hours After Cardiopulmonary Pulmonary Bypass (CPB) | AKI Stage 0 | 7 Participants |
p-value: 0.517Chi-squared
Secondary
Initiation of Renal Replacement Therapy
Initiation of Renal Replacement Therapy up to 48 Hours post CPB
Time frame: Up to 48 hours after CPB
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CytoSorb Device | Initiation of Renal Replacement Therapy | 0 Participants |
| Control | Initiation of Renal Replacement Therapy | 3 Participants |
| Roll In: CytoSorb Device | Initiation of Renal Replacement Therapy | 0 Participants |
Secondary
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.
Time frame: From start of CPB through discharge, average of 8.9 days.
Population: safety population analysis. Not all patients' data complete.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| CytoSorb Device | Summary of Health Resource Utilization: Duration of Continuous Intra-op to Post-op Ventilator/ Mechanical Support Use | 12.83 hours | Standard Deviation 19.12 |
| Control | Summary of Health Resource Utilization: Duration of Continuous Intra-op to Post-op Ventilator/ Mechanical Support Use | 11.62 hours | Standard Deviation 60.38 |
| Roll In: CytoSorb Device | Summary of Health Resource Utilization: Duration of Continuous Intra-op to Post-op Ventilator/ Mechanical Support Use | 13.30 hours | Standard Deviation 77.73 |
Secondary
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.
Time frame: From start of CPB through discharge, average of 8.9 days.
Population: safety population analysis. Not all patients' data complete.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| CytoSorb Device | Summary of Health Resource Utilization: ICU Duration (Hours) | 70.63 hours | Standard Deviation 85.55 |
| Control | Summary of Health Resource Utilization: ICU Duration (Hours) | 53.57 hours | Standard Deviation 67.6 |
| Roll In: CytoSorb Device | Summary of Health Resource Utilization: ICU Duration (Hours) | 66.83 hours | Standard Deviation 132.87 |
Secondary
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.
Time frame: From start of CPB through discharge, average of 8.9 days.
Population: safety population analysis. Not all patients' data complete.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CytoSorb Device | Summary of Health Resource Utilization: Number of Patients on Vasopressor Medication | 44 Participants |
| Control | Summary of Health Resource Utilization: Number of Patients on Vasopressor Medication | 48 Participants |
| Roll In: CytoSorb Device | Summary of Health Resource Utilization: Number of Patients on Vasopressor Medication | 32 Participants |
Secondary
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.
Time frame: From start of CPB through discharge, average of 8.9 days.
Population: safety population analysis. Not all patients' data complete.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| CytoSorb Device | Summary of Health Resource Utilization: Post-Op Hospital Stay: Date of Discharge - Date of ICU Admission | 8 days | Standard Deviation 3.9 |
| Control | Summary of Health Resource Utilization: Post-Op Hospital Stay: Date of Discharge - Date of ICU Admission | 7 days | Standard Deviation 4.7 |
| Roll In: CytoSorb Device | Summary of Health Resource Utilization: Post-Op Hospital Stay: Date of Discharge - Date of ICU Admission | 7 days | Standard Deviation 5.2 |