Back to resultsRed Cell Rejuvenation for the Attenuation of Transfusion Associated Organ Injury in Cardiac Surgery
Primary Purpose
Organ Failure, Multiple, Inflammation, Sepsis
Status
Withdrawn
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
rejuvesol Solution
Standard Care
Sponsored by
About this trial
This is an interventional prevention trial for Organ Failure, Multiple
Eligibility Criteria
Inclusion Criteria:
- Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery with cardiopulmonary bypass.
- Identified as representing a high risk group for massive blood transfusion using a modified risk score. A large volume blood transfusion (LVBT) score of >23 indicates predicted risk of receiving ≥4 units of allogeneic red cells equal to or greater than 55 per cent.
Exclusion Criteria:
- Emergency or salvage procedure
- Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.72 m2 calculated from the Modification of Diet in Renal Disease equation, or patients who are on long-term haemodialysis or have undergone renal transplantation.
- Patients who are prevented from having blood and blood products according to a system of beliefs (e.g. Jehovah's Witnesses).
- Patients with a pre-existing sepsis or organ injury defined as documented sepsis, acute kidney injury, acute lung injury, myocardial infarction, low cardiac output, liver injury, stroke or pancreatitis within 5 days of surgery.
- Pregnancy.
- Patients who are participating in another interventional clinical study.
- Patients requiring irradiated blood.
- Sickle cell anaemia.
Sites / Locations
- Department of Cardiovascular Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Intervention
Control
Arm Description
Cross-matched allogeneic stored red cells will be rejuvenated using rejuvesol® Red Blood Cell Processing Solution (Citra Labs, MA, a Zimmer Biomet Company, IN, USA) with washing and re-suspension in an additive solution prior to transfusion. The rejuvenated red cells will then be administered to the patient as per standard practice and according to established institutional protocols. A maximum of 6 rejuvenated red cell units will be transfused within any 24 hour period.
Standard care i.e. Cross-matched allogeneic stored non-rejuvenated, unwashed red cells will be administered to the patient as per standard practice and according to established institutional protocols.
Outcomes
Primary Outcome Measures
Renal injury
measurement of serum creatinine
Myocardial injury
measurement of serum troponin
Secondary Outcome Measures
Protocol compliance measured through protocol deviations
protocol deviations will be aggregated based on pre-defined codes
Recruitment
measured through recruitment figures
Event rates
measured through serious adverse event (SAE)/ serious unexpected serious adverse reaction (SUSAR) reporting
Blinding
measured through protocol deviations
Urinary neutrophil gelatinase associated lipocalin (NGAL)
measured through urine collection
Serum creatinine
measured to assess renal function
eGFR
measured to assess renal function
Sepsis-related Organ Failure Assessment (SOFA) Score
Sepsis will be defined as suspected or documented infection and an acute change in total SOFA score ≥2 points consequent to the infection.
Arterial serum lactate
Lung injury
arterial alveolar oxygen ratios
GI tract injury
serum amylase and liver function tests
Transfusion reactions
measured as part of standard care to assess transfusion safety
Age of each unit of red cells transfused
Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components
Adverse events other than those included in the primary endpoint
Length of ICU and hospital stay
Full Information
NCT ID
NCT03167788
First Posted
May 12, 2017
Last Updated
April 27, 2021
Sponsor
University of Leicester
Collaborators
National Health Service, United Kingdom, Zimmer Biomet, British Heart Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03167788
Brief Title
Red Cell Rejuvenation for the Attenuation of Transfusion Associated Organ Injury in Cardiac Surgery
Official Title
A RANDOMISED CONTROLLED TRIAL OF RED CELL REJUVENATION FOR THE ATTENUATION OF TRANSFUSION ASSOCIATED ORGAN INJURY IN CARDIAC SURGERY: The REDJUVENATE Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Manufacturing Issues
Study Start Date
December 2020 (Anticipated)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Leicester
Collaborators
National Health Service, United Kingdom, Zimmer Biomet, British Heart Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The REDJUVENATE Trial proposes to test the hypothesis that postoperative organ injury and inflammation will be less if patients undergoing cardiac surgery who are at risk of large volume blood transfusion (defined as the administration of ≥4 units of red cells) receive rejuvenated washed cells compared to standard care (unwashed aged stored cells).
Detailed Description
In the REDJUVENATE trial, we propose to establish whether the administration of rejuvenated red cells will reduce inflammation and organ injury in cardiac surgery patients at risk of large volume blood transfusion when compared to standard care. Organ injury and sepsis accounts for the majority of all deaths following cardiac surgery. Once organ injury is established care is primarily supportive and there are no effective treatments. Prevention is therefore a key clinical strategy to prevent death, morbidity and high healthcare costs attributable to these complications. Sepsis and inflammatory organ injury are also the principal causes of death following paediatric cardiac surgery, trauma, non-cardiac complex surgical procedures and in critical care; clinical settings that are also among the principal consumers of blood components. National and international blood management strategies are focused on these patients. Evidence of a clinical benefit attributable to the use of rejuvenated red cells in cardiac surgery patients is therefore likely to translate into more widespread benefits to patients and the National Health Service (NHS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Organ Failure, Multiple, Inflammation, Sepsis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Experimental
Arm Description
Cross-matched allogeneic stored red cells will be rejuvenated using rejuvesol® Red Blood Cell Processing Solution (Citra Labs, MA, a Zimmer Biomet Company, IN, USA) with washing and re-suspension in an additive solution prior to transfusion. The rejuvenated red cells will then be administered to the patient as per standard practice and according to established institutional protocols. A maximum of 6 rejuvenated red cell units will be transfused within any 24 hour period.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Standard care i.e. Cross-matched allogeneic stored non-rejuvenated, unwashed red cells will be administered to the patient as per standard practice and according to established institutional protocols.
Intervention Type
Device
Intervention Name(s)
rejuvesol Solution
Intervention Description
The rejuvenation process involves incubation of stored red cells with a rejuvenating solution, rejuvesol Red Blood Cell Processing Solution (rejuvesol® Solution), Citra labs, MA, a Zimmer Biomet Company, IN, USA) which restores red cell adenosine triphosphate (ATP), 2,3-DPG (diphosphoglycerate), oxygen transfer characteristics and rheology. Post rejuvenation red cells are washed to remove the rejuvesol Solution, and cells are re-suspended in additive solution for transfusion.
Intervention Type
Other
Intervention Name(s)
Standard Care
Intervention Description
Allogeneic red cells, harvested in citrate-phosphate-dextrose (CPD), leucocyte depleted, saline-adenine-glucose-mannitol (SAGM) stored red cell units, issued by National Health Service Blood & Transplant (NHSBT) will be administered to cardiac surgery patients as per standard practice, and according to established unit protocols.
Primary Outcome Measure Information:
Title
Renal injury
Description
measurement of serum creatinine
Time Frame
baseline to 96 hours postoperatively
Title
Myocardial injury
Description
measurement of serum troponin
Time Frame
baseline to 72 hours postoperatively
Secondary Outcome Measure Information:
Title
Protocol compliance measured through protocol deviations
Description
protocol deviations will be aggregated based on pre-defined codes
Time Frame
from date of randomisation through to study completion (3 months)
Title
Recruitment
Description
measured through recruitment figures
Time Frame
from date of randomisation through to study completion (3 months)
Title
Event rates
Description
measured through serious adverse event (SAE)/ serious unexpected serious adverse reaction (SUSAR) reporting
Time Frame
from date of randomisation through to study completion (3 months)
Title
Blinding
Description
measured through protocol deviations
Time Frame
from date of randomisation through to study completion (3 months)
Title
Urinary neutrophil gelatinase associated lipocalin (NGAL)
Description
measured through urine collection
Time Frame
baseline to 48 hours postoperatively
Title
Serum creatinine
Description
measured to assess renal function
Time Frame
at 6 weeks postoperatively
Title
eGFR
Description
measured to assess renal function
Time Frame
at 6 weeks postoperatively
Title
Sepsis-related Organ Failure Assessment (SOFA) Score
Description
Sepsis will be defined as suspected or documented infection and an acute change in total SOFA score ≥2 points consequent to the infection.
Time Frame
at baseline, 24, 48, 72 and 96 hours postoperatively
Title
Arterial serum lactate
Time Frame
24 hours postoperatively until time of resolution of hyperlactataemia
Title
Lung injury
Description
arterial alveolar oxygen ratios
Time Frame
baseline to 96 hours postoperatively
Title
GI tract injury
Description
serum amylase and liver function tests
Time Frame
at baseline, 24, 48, 72, and 96 hours postoperatively
Title
Transfusion reactions
Description
measured as part of standard care to assess transfusion safety
Time Frame
from date of randomisation through to study completion (3 months)
Title
Age of each unit of red cells transfused
Time Frame
day of operation
Title
Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components
Time Frame
day of operation
Title
Adverse events other than those included in the primary endpoint
Time Frame
from date of randomisation through to study completion (3 months)
Title
Length of ICU and hospital stay
Time Frame
from date of randomisation through to study completion (3 months)
Other Pre-specified Outcome Measures:
Title
Acute lung injury
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Acute kidney injury
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Low cardiac output
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Acute brain injury
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Acute liver or gut injury
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Sepsis
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Organ injury, sepsis or death (a composite of sepsis, acute kidney injury, acute lung injury, acute brain injury, low cardiac output syndrome, gut or liver injury or death)
Description
To inform the design of a subsequent efficacy trial
Time Frame
from date of randomisation through to study completion (3 months)
Title
Endothelial function, tissue hypoxia and p50 of circulating red cells
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline and 24 hours post-op
Title
Recipient platelet, monocyte and endothelial activation in whole blood as determined using flow cytometry
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 48 hours post-op
Title
Bronchial aspirate neutrophil and protein concentration
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
4-6 hours post-op
Title
free haem
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
Title
serum bilirubin
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
Title
transferrin saturation
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
Title
non-transferrin bound iron
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
Title
hepcidin
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
Title
pulmonary leucocyte haem oxygenase-1 expression
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
Title
serum protein carbonylation and lipid peroxidation
Description
To be measured in a sub-study of mechanisms in 80 participants
Time Frame
baseline to 96 hours post-op
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery with cardiopulmonary bypass.
Identified as representing a high risk group for massive blood transfusion using a modified risk score. A large volume blood transfusion (LVBT) score of >23 indicates predicted risk of receiving ≥4 units of allogeneic red cells equal to or greater than 55 per cent.
Exclusion Criteria:
Emergency or salvage procedure
Patients with end stage renal failure defined as an estimated Glomerular Filtration rate (eGFR) <15 mL/min/1.72 m2 calculated from the Modification of Diet in Renal Disease equation, or patients who are on long-term haemodialysis or have undergone renal transplantation.
Patients who are prevented from having blood and blood products according to a system of beliefs (e.g. Jehovah's Witnesses).
Patients with a pre-existing sepsis or organ injury defined as documented sepsis, acute kidney injury, acute lung injury, myocardial infarction, low cardiac output, liver injury, stroke or pancreatitis within 5 days of surgery.
Pregnancy.
Patients who are participating in another interventional clinical study.
Patients requiring irradiated blood.
Sickle cell anaemia.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gavin J Murphy, Prof
Organizational Affiliation
University of Leicester
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiovascular Sciences
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Red Cell Rejuvenation for the Attenuation of Transfusion Associated Organ Injury in Cardiac Surgery
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