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

NCT ID: NCT03167788

Last Updated: 2021-04-29

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-31
• Study Completion Date: 2020-12-31

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).

Conditions

Organ Failure, Multiple; Inflammation; Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

rejuvesol Solution

Intervention Type: DEVICE

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.

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.

Group Type: ACTIVE_COMPARATOR

Standard Care

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DEVICE

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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health Service, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

Zimmer Biomet

INDUSTRY

Sponsor Role: collaborator

British Heart Foundation

OTHER

Sponsor Role: collaborator

University of Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gavin J Murphy, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

Department of Cardiovascular Sciences

Leicester, Leicestershire, United Kingdom

Countries

United Kingdom

Other Identifiers

0582

Identifier Type: -

Identifier Source: org_study_id