Red Cell Rejuvenation for the Attenuation of Transfusion Associated Organ Injury in Cardiac Surgery

April 27, 2021 updated by: University of Leicester

A RANDOMISED CONTROLLED TRIAL OF RED CELL REJUVENATION FOR THE ATTENUATION OF TRANSFUSION ASSOCIATED ORGAN INJURY IN CARDIAC SURGERY: The REDJUVENATE Trial

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • Department of Cardiovascular Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adult cardiac surgery patients (≥18 years) undergoing cardiac surgery with cardiopulmonary bypass.
  2. 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:

  1. Emergency or salvage procedure
  2. 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.
  3. Patients who are prevented from having blood and blood products according to a system of beliefs (e.g. Jehovah's Witnesses).
  4. 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.
  5. Pregnancy.
  6. Patients who are participating in another interventional clinical study.
  7. Patients requiring irradiated blood.
  8. Sickle cell anaemia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Intervention
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.
Device: rejuvesol Solution
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.
ACTIVE_COMPARATOR: Control
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.
Other: Standard Care
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Renal injury
Time Frame: baseline to 96 hours postoperatively
measurement of serum creatinine
baseline to 96 hours postoperatively
Myocardial injury
Time Frame: baseline to 72 hours postoperatively
measurement of serum troponin
baseline to 72 hours postoperatively

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Protocol compliance measured through protocol deviations
Time Frame: from date of randomisation through to study completion (3 months)
protocol deviations will be aggregated based on pre-defined codes
from date of randomisation through to study completion (3 months)
Recruitment
Time Frame: from date of randomisation through to study completion (3 months)
measured through recruitment figures
from date of randomisation through to study completion (3 months)
Event rates
Time Frame: from date of randomisation through to study completion (3 months)
measured through serious adverse event (SAE)/ serious unexpected serious adverse reaction (SUSAR) reporting
from date of randomisation through to study completion (3 months)
Blinding
Time Frame: from date of randomisation through to study completion (3 months)
measured through protocol deviations
from date of randomisation through to study completion (3 months)
Urinary neutrophil gelatinase associated lipocalin (NGAL)
Time Frame: baseline to 48 hours postoperatively
measured through urine collection
baseline to 48 hours postoperatively
Serum creatinine
Time Frame: at 6 weeks postoperatively
measured to assess renal function
at 6 weeks postoperatively
eGFR
Time Frame: at 6 weeks postoperatively
measured to assess renal function
at 6 weeks postoperatively
Sepsis-related Organ Failure Assessment (SOFA) Score
Time Frame: at baseline, 24, 48, 72 and 96 hours postoperatively
Sepsis will be defined as suspected or documented infection and an acute change in total SOFA score ≥2 points consequent to the infection.
at baseline, 24, 48, 72 and 96 hours postoperatively
Arterial serum lactate
Time Frame: 24 hours postoperatively until time of resolution of hyperlactataemia
24 hours postoperatively until time of resolution of hyperlactataemia
Lung injury
Time Frame: baseline to 96 hours postoperatively
arterial alveolar oxygen ratios
baseline to 96 hours postoperatively
GI tract injury
Time Frame: at baseline, 24, 48, 72, and 96 hours postoperatively
serum amylase and liver function tests
at baseline, 24, 48, 72, and 96 hours postoperatively
Transfusion reactions
Time Frame: from date of randomisation through to study completion (3 months)
measured as part of standard care to assess transfusion safety
from date of randomisation through to study completion (3 months)
Age of each unit of red cells transfused
Time Frame: day of operation
day of operation
Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components
Time Frame: day of operation
day of operation
Adverse events other than those included in the primary endpoint
Time Frame: from date of randomisation through to study completion (3 months)
from date of randomisation through to study completion (3 months)
Length of ICU and hospital stay
Time Frame: from date of randomisation through to study completion (3 months)
from date of randomisation through to study completion (3 months)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Acute lung injury
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
Acute kidney injury
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
Low cardiac output
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
Acute brain injury
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
Acute liver or gut injury
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
Sepsis
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
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)
Time Frame: from date of randomisation through to study completion (3 months)
To inform the design of a subsequent efficacy trial
from date of randomisation through to study completion (3 months)
Endothelial function, tissue hypoxia and p50 of circulating red cells
Time Frame: baseline and 24 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline and 24 hours post-op
Recipient platelet, monocyte and endothelial activation in whole blood as determined using flow cytometry
Time Frame: baseline to 48 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 48 hours post-op
Bronchial aspirate neutrophil and protein concentration
Time Frame: 4-6 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
4-6 hours post-op
free haem
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op
serum bilirubin
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op
transferrin saturation
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op
non-transferrin bound iron
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op
hepcidin
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op
pulmonary leucocyte haem oxygenase-1 expression
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op
serum protein carbonylation and lipid peroxidation
Time Frame: baseline to 96 hours post-op
To be measured in a sub-study of mechanisms in 80 participants
baseline to 96 hours post-op

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Leicester

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Zimmer Biomet
British Heart Foundation
National Health Service, United Kingdom

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2020

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 12, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 29, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0582

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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