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

Phase 2

Withdrawn

• Conditions: Organ Failure, Multiple; Inflammation; Sepsis
• Interventions: Device: rejuvesol Solution; Other: Standard Care

• Registration Number: NCT03167788
• Lead Sponsor: University of Leicester

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).

Study Timeline

• Study First Submitted: 2017-05-12
• Study First Submitted QC: 2017-05-23
• Study First Posted: 2017-05-30
• Status Verified: 2020-05
• Study Start: 2020-12
• Primary Completion: 2020-12
• Study Completion: 2020-12
• Last Update Submitted: 2021-04-27
• Last Update Posted: 2021-04-29

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	rejuvesol Solution	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.
Control	Standard Care	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.

Primary Outcome Measures

Name	Time	Method
Myocardial injury	baseline to 72 hours postoperatively	measurement of serum troponin
Renal injury	baseline to 96 hours postoperatively	measurement of serum creatinine

Secondary Outcome Measures

Name	Time	Method
Urinary neutrophil gelatinase associated lipocalin (NGAL)	baseline to 48 hours postoperatively	measured through urine collection
Sepsis-related Organ Failure Assessment (SOFA) Score	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.
Arterial serum lactate	24 hours postoperatively until time of resolution of hyperlactataemia
Age of each unit of red cells transfused	day of operation
Event rates	from date of randomisation through to study completion (3 months)	measured through serious adverse event (SAE)/ serious unexpected serious adverse reaction (SUSAR) reporting
Serum creatinine	at 6 weeks postoperatively	measured to assess renal function
Recruitment	from date of randomisation through to study completion (3 months)	measured through recruitment figures
eGFR	at 6 weeks postoperatively	measured to assess renal function
GI tract injury	at baseline, 24, 48, 72, and 96 hours postoperatively	serum amylase and liver function tests
Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components	day of operation
Length of ICU and hospital stay	from date of randomisation through to study completion (3 months)
Blinding	from date of randomisation through to study completion (3 months)	measured through protocol deviations
Protocol compliance measured through protocol deviations	from date of randomisation through to study completion (3 months)	protocol deviations will be aggregated based on pre-defined codes
Adverse events other than those included in the primary endpoint	from date of randomisation through to study completion (3 months)
Lung injury	baseline to 96 hours postoperatively	arterial alveolar oxygen ratios
Transfusion reactions	from date of randomisation through to study completion (3 months)	measured as part of standard care to assess transfusion safety

Trial Locations

Locations (1)

Department of Cardiovascular Sciences; 🇬🇧 Leicester, Leicestershire, United Kingdom