Hypoxic Red Blood Cells for Burns and Hematological Malignancies at Haukeland University Hospital

Study Overview
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Brief Summary
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The overall objective of this study is to collect preliminary safety data on the transfusion of hypoxic RBCs, manufactured with the Hemanext ONE device, in patients with burns and patients with hematological malignancies. The Hemanext ONE device received CE mark in April 2021.

Detailed Description
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The primary objective is to assess hypoxic RBCs safety and tolerance assessment up to 24 hours following the transfusion initiation and overall up to 7 days (+/- 1 day) after the transfusion episode (single transfusion course). Secondary objectives include the following. Assessment of pre and post transfusion hemoglobin levels Assessment of hemoglobin level before the following transfusion, if applicable Assessment of AEs occurrence: i. Up to 7 days (+/- 1 day) post transfusion, in comparison with historical control (including but not limited to infection, deep vein thrombosis, acute respiratory distress syndrome, transfusion-related acute lung injury, transfusion associated circulatory overload, anaphylactic shock, acute hemolytic transfusion reaction). ii. Up to the subsequent transfusion episode or up to 28 days (+/- 1 day) after the initial transfusion, whichever comes first. iii. From enrollment, up to their subsequent transfusion or 28 days (+/- 1 day) post transfusion, whichever comes first, through the assessment of patient's diary. Assessment of the vital signs during and up to 15 minutes after the transfusion.

Official Title
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A Single Center, Pilot Clinical Investigation of Surgical Bleeding in Burn Patients, and Chronically Transfused Patients With Haematologic Malignancies, Who Are Transfused With Hypoxic Red Blood Cells Manufactured With Hemanext ONE System

Conditions
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Burns, Hematologic Neoplasms

Intervention / Treatment
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* Device: Hypoxic Red Blood Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A. Hematological malignancies patients group: Male or female patients at least 18 years of age Patients expected to require > 2 units of red blood cells in a single transfusion event Patients who have the capacity to consent to participate and are willing to comply with the study procedures. Patients identified by a Transfusion hemoglobin trigger of less than 9 g/dL Patients with a documented diagnosis of leukemia, myelomatosis or MDS requiring chronic transfusions B. Burn patients group: Male or female patients at least 18 years of age Patients who have the capacity to consent by themselves to participate to the clinical investigation Smaller burn patients, hospitalized with a Total Body Surface Area (TBSA%) burn ≥ 10% and ≤ 50% Patients expected to require > 2 unit of red blood cells in a single transfusion event Exclusion Criteria: A. Both patients groups Patients with any positive antibody screening test Patients for whom consent has not been obtained Patients with a known hemolytic anemia (congenital or acquired) Patients < 18 years old Patients with a known or suspected pregnancy Patients with a history of major transfusion reactions Patients whom the Investigator deems clinical trial participation is not in their best interest. B. Burn patients specific exclusion criteria : Patients who do not have the capacity to consent by themselves to participate to the clinical investigation Patients hospitalized with a Total body surface area (TBSA%) burn more than 50% Patients with combined trauma in need of blood transfusions for treatment other than the burn excision

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hematologic Malignancies<br>Subjects requiring chronic transfusions with red blood cells for treatment of a hematologic malignancy will receive 1 transfusion with 2 units of hypoxic red blood cells manufactured with the Hemanext ONE device. The subjects will be monitored for all adverse events from Informed Consent through Day 28 or the subsequent standard of care transfusion, whichever occurs first. | Device: Hypoxic Red Blood Cells<br>* Hypoxic Red Blood Cells manufactured with the Hemanext ONE device- CPD/PAGGSM Red Blood Cells, Leukocytes Reduced, and O2/CO2 Reduced<br>|
| Acute Burn<br>Subjects requiring transfusion with red blood cells during the excision procedure after an acute burn will receive 2 units of hypoxic red blood cells manufactured with the Hemanext ONE device. As the excision treatments require transfusion of more than 2 units of red blood cells, the first 2 units transfused during the procedure will be hypoxic red blood cells. The subjects will be monitored for all adverse events through Day 28. | Device: Hypoxic Red Blood Cells<br>* Hypoxic Red Blood Cells manufactured with the Hemanext ONE device- CPD/PAGGSM Red Blood Cells, Leukocytes Reduced, and O2/CO2 Reduced<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who experienced an adverse event (all types/grades) within a time frame up to 24 hours following the transfusion and overall up to 7 days (+/- 1 day) after the transfusion. | The type and the grade of each adverse event will be categorized according to: Association for the Advancement of Blood and Biotherapies (AABB) technical manual, 20th edition (2020) Biomedical Excellence for Safer Transfusion (BEST) Collaborative review - Lancet 2016; 388: 2825-36 Local AEs database (for reference) ISO 14155-2020 definitions | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the hemoglobin level before and after the transfusion. | The difference in measured hemoglobin (grams/dL) between pre-transfusion and up to 30 minutes post-transfusion. | 1 days | 
| Calculation of the Hemoglobin increment after transfusion corrected for patient blood volume and hemoglobin dose | The hemoglobin increment from each transfusion will be determined by calculating the difference between the subject's post-transfusion and pre-transfusion hemoglobin (g/dL). It will then be corrected for estimated subject blood volume and the amount of Hb transfused. The following equation used for the hemoglobin increment calculation: HgB Increment = (Subject's HgB level post-transfusion - Subject's HgB pre-transfusion)/ (total HgB transfused x Subject's BloodVolume) Equations for calculating the hemoglobin increment may be found in the following publication: Wendelbo Ø, Opheim EN, Hervig T, Felli Lunde TH, Bruserud Ø, Mollnes TE, Reikvam H. Cytokine profiling and post-transfusion haemoglobin increment in patients with haematological diseases. Vox Sang. 2018 Oct;113(7):657-668. doi: 10.1111/vox.12703. Epub 2018 Aug 29. PMID: 30159896. | 28 days | 
| Comparison of the Hemoglobin level before the index transfusion to that prior to the subsequent transfusion (hematologic malignancy group only) | The difference in measured hemoglobin (grams/dL) between the pre-transfusion hemoglobin level for the study transfusion and the pre-transfusion hemoglobin level for the next scheduled transfusion. | 28 days | 
| Evaluation of AEs from enrollment, up to prior to the subsequent transfusion or up to Day 28, whichever occurs first | The type and the grade of each adverse event will be categorized according to: Association for the Advancement of Blood and Biotherapies (AABB) technical manual, 20th edition (2020) Biomedical Excellence for Safer Transfusion (BEST) Collaborative review - Lancet 2016; 388: 2825-36 Local AEs database (for reference) ISO 14155-2020 definitions | 28 days | 
| Evaluation of subject's blood pressure over the course of the transfusion and up to 15 minutes post-transfusion | Review of blood pressure (systolic/diastolic; mmHg) throughout the study transfusion. | 1 day | 
| Evaluation of subject's respiratory rate over the course of the transfusion and up to 15 minutes post-transfusion | Review of respiratory rate (breaths per minute) throughout the study transfusion. | 1 day | 
| Evaluation of subject's SO2 level over the course of the transfusion and up to 15 minutes post-transfusion | Review of amount of oxygen in the body (% S02 level) measured with a pulse oximeter throughout the study transfusion. | 1 day | 
| Evaluation of subject's pulse over the course of the transfusion and up to 15 minutes post-transfusion | Review of heart rate (beats per minute) throughout the study transfusion. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transfusion, Red Blood Cells, Hypoxic