Clinical trial NCT03167788: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Organ Failure, Multiple
Inflammation
Sepsis
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: National Health Service, United Kingdom
name: Zimmer Biomet
name: British Heart Foundation
First posted: 2017-05-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Renal injury
timeFrame: baseline to 96 hours postoperatively
measure: Myocardial injury
timeFrame: baseline to 72 hours postoperatively
Secondary outcomes:
measure: Protocol compliance measured through protocol deviations
timeFrame: from date of randomisation through to study completion (3 months)
measure: Recruitment
timeFrame: from date of randomisation through to study completion (3 months)
measure: Event rates
timeFrame: from date of randomisation through to study completion (3 months)
measure: Blinding
timeFrame: from date of randomisation through to study completion (3 months)
measure: Urinary neutrophil gelatinase associated lipocalin (NGAL)
timeFrame: baseline to 48 hours postoperatively
measure: Serum creatinine
timeFrame: at 6 weeks postoperatively
measure: eGFR
timeFrame: at 6 weeks postoperatively
measure: Sepsis-related Organ Failure Assessment (SOFA) Score
timeFrame: at baseline, 24, 48, 72 and 96 hours postoperatively
measure: Arterial serum lactate
timeFrame: 24 hours postoperatively until time of resolution of hyperlactataemia
measure: Lung injury
timeFrame: baseline to 96 hours postoperatively
measure: GI tract injury
timeFrame: at baseline, 24, 48, 72, and 96 hours postoperatively
measure: Transfusion reactions
timeFrame: from date of randomisation through to study completion (3 months)
measure: Age of each unit of red cells transfused
timeFrame: day of operation
measure: Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components
timeFrame: day of operation
measure: Adverse events other than those included in the primary endpoint
timeFrame: from date of randomisation through to study completion (3 months)
measure: Length of ICU and hospital stay
timeFrame: from date of randomisation through to study completion (3 months)
Other outcomes:
measure: Acute lung injury
timeFrame: from date of randomisation through to study completion (3 months)
measure: Acute kidney injury
timeFrame: from date of randomisation through to study completion (3 months)
measure: Low cardiac output
timeFrame: from date of randomisation through to study completion (3 months)
measure: Acute brain injury
timeFrame: from date of randomisation through to study completion (3 months)
measure: Acute liver or gut injury
timeFrame: from date of randomisation through to study completion (3 months)
measure: Sepsis
timeFrame: from date of randomisation through to study completion (3 months)
measure: 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)
timeFrame: from date of randomisation through to study completion (3 months)
measure: Endothelial function, tissue hypoxia and p50 of circulating red cells
timeFrame: baseline and 24 hours post-op
measure: Recipient platelet, monocyte and endothelial activation in whole blood as determined using flow cytometry
timeFrame: baseline to 48 hours post-op
measure: Bronchial aspirate neutrophil and protein concentration
timeFrame: 4-6 hours post-op
measure: free haem
timeFrame: baseline to 96 hours post-op
measure: serum bilirubin
timeFrame: baseline to 96 hours post-op
measure: transferrin saturation
timeFrame: baseline to 96 hours post-op
measure: non-transferrin bound iron
timeFrame: baseline to 96 hours post-op
measure: hepcidin
timeFrame: baseline to 96 hours post-op
measure: pulmonary leucocyte haem oxygenase-1 expression
timeFrame: baseline to 96 hours post-op
measure: serum protein carbonylation and lipid peroxidation
timeFrame: baseline to 96 hours post-op
Locations:
city: Leicester
country: United Kingdom
facility: Department of Cardiovascular Sciences
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Gavin J Murphy, Prof
role: PRINCIPAL_INVESTIGATOR
References: