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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03167788
• Other study ID #: 0582
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2020
• Est. completion date: December 2020

Study information

• Verified date: May 2020
• Source: University of Leicester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Inflammation
• Multiple Organ Failure
• Organ Failure, Multiple
• Sepsis

Intervention

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.

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.

Locations

Country	Name	City	State
United Kingdom	Department of Cardiovascular Sciences	Leicester	Leicestershire

Sponsors (4)

Lead Sponsor	Collaborator
University of Leicester	British Heart Foundation, National Health Service, United Kingdom, Zimmer Biomet

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Acute lung injury	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	Acute kidney injury	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	Low cardiac output	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	Acute brain injury	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	Acute liver or gut injury	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	Sepsis	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	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)	To inform the design of a subsequent efficacy trial	from date of randomisation through to study completion (3 months)
Other	Endothelial function, tissue hypoxia and p50 of circulating red cells	To be measured in a sub-study of mechanisms in 80 participants	baseline and 24 hours post-op
Other	Recipient platelet, monocyte and endothelial activation in whole blood as determined using flow cytometry	To be measured in a sub-study of mechanisms in 80 participants	baseline to 48 hours post-op
Other	Bronchial aspirate neutrophil and protein concentration	To be measured in a sub-study of mechanisms in 80 participants	4-6 hours post-op
Other	free haem	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Other	serum bilirubin	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Other	transferrin saturation	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Other	non-transferrin bound iron	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Other	hepcidin	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Other	pulmonary leucocyte haem oxygenase-1 expression	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Other	serum protein carbonylation and lipid peroxidation	To be measured in a sub-study of mechanisms in 80 participants	baseline to 96 hours post-op
Primary	Renal injury	measurement of serum creatinine	baseline to 96 hours postoperatively
Primary	Myocardial injury	measurement of serum troponin	baseline to 72 hours postoperatively
Secondary	Protocol compliance measured through protocol deviations	protocol deviations will be aggregated based on pre-defined codes	from date of randomisation through to study completion (3 months)
Secondary	Recruitment	measured through recruitment figures	from date of randomisation through to study completion (3 months)
Secondary	Event rates	measured through serious adverse event (SAE)/ serious unexpected serious adverse reaction (SUSAR) reporting	from date of randomisation through to study completion (3 months)
Secondary	Blinding	measured through protocol deviations	from date of randomisation through to study completion (3 months)
Secondary	Urinary neutrophil gelatinase associated lipocalin (NGAL)	measured through urine collection	baseline to 48 hours postoperatively
Secondary	Serum creatinine	measured to assess renal function	at 6 weeks postoperatively
Secondary	eGFR	measured to assess renal function	at 6 weeks postoperatively
Secondary	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.	at baseline, 24, 48, 72 and 96 hours postoperatively
Secondary	Arterial serum lactate		24 hours postoperatively until time of resolution of hyperlactataemia
Secondary	Lung injury	arterial alveolar oxygen ratios	baseline to 96 hours postoperatively
Secondary	GI tract injury	serum amylase and liver function tests	at baseline, 24, 48, 72, and 96 hours postoperatively
Secondary	Transfusion reactions	measured as part of standard care to assess transfusion safety	from date of randomisation through to study completion (3 months)
Secondary	Age of each unit of red cells transfused		day of operation
Secondary	Postoperative blood loss, transfusion of red cell and non-red cell allogenic blood components		day of operation
Secondary	Adverse events other than those included in the primary endpoint		from date of randomisation through to study completion (3 months)
Secondary	Length of ICU and hospital stay		from date of randomisation through to study completion (3 months)