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).
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
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.
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.
Department of Cardiovascular Sciences
Leicester, Leicestershire, United Kingdom
Renal injury
measurement of serum creatinine
Time frame: baseline to 96 hours postoperatively
Myocardial injury
measurement of serum troponin
Time frame: baseline to 72 hours postoperatively
Protocol compliance measured through protocol deviations
protocol deviations will be aggregated based on pre-defined codes
Time frame: from date of randomisation through to study completion (3 months)
Recruitment
measured through recruitment figures
Time frame: from date of randomisation through to study completion (3 months)
Event rates
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)
Blinding
measured through protocol deviations
Time frame: from date of randomisation through to study completion (3 months)
Urinary neutrophil gelatinase associated lipocalin (NGAL)
measured through urine collection
Time frame: baseline to 48 hours postoperatively
Serum creatinine
measured to assess renal function
Time frame: at 6 weeks postoperatively
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eGFR
measured to assess renal function
Time frame: at 6 weeks postoperatively
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.
Time frame: at baseline, 24, 48, 72 and 96 hours postoperatively
Arterial serum lactate
Time frame: 24 hours postoperatively until time of resolution of hyperlactataemia
Lung injury
arterial alveolar oxygen ratios
Time frame: baseline to 96 hours postoperatively
GI tract injury
serum amylase and liver function tests
Time frame: at baseline, 24, 48, 72, and 96 hours postoperatively
Transfusion reactions
measured as part of standard care to assess transfusion safety
Time frame: from date of randomisation through to study completion (3 months)
Age of each unit of red cells transfused
Time frame: day of operation
Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components
Time frame: 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)
Length of ICU and hospital stay
Time frame: from date of randomisation through to study completion (3 months)