Burns, Hematologic Neoplasms
Conditions
Keywords
Transfusion, Red Blood Cells, Hypoxic
Brief summary
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
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. 1. Assessment of pre and post transfusion hemoglobin levels 2. Assessment of hemoglobin level before the following transfusion, if applicable 3. 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. 4. Assessment of the vital signs during and up to 15 minutes after the transfusion.
Interventions
DEVICEHypoxic Red Blood Cells
Hypoxic Red Blood Cells manufactured with the Hemanext ONE device- CPD/PAGGSM Red Blood Cells, Leukocytes Reduced, and O2/CO2 Reduced
Sponsors
Hemanext
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A. Hematological malignancies patients group: 1. Male or female patients at least 18 years of age 2. Patients expected to require \> 2 units of red blood cells in a single transfusion event 3. Patients who have the capacity to consent to participate and are willing to comply with the study procedures. 4. Patients identified by a Transfusion hemoglobin trigger of less than 9 g/dL 5. Patients with a documented diagnosis of leukemia, myelomatosis or MDS requiring chronic transfusions B. Burn patients group: 1. Male or female patients at least 18 years of age 2. Patients who have the capacity to consent by themselves to participate to the clinical investigation 3. Smaller burn patients, hospitalized with a Total Body Surface Area (TBSA%) burn ≥ 10% and ≤ 50% 4. Patients expected to require \> 2 unit of red blood cells in a single transfusion event
Exclusion criteria
A. Both patients groups 1. Patients with any positive antibody screening test 2. Patients for whom consent has not been obtained 3. Patients with a known hemolytic anemia (congenital or acquired) 4. Patients \< 18 years old 5. Patients with a known or suspected pregnancy 6. Patients with a history of major transfusion reactions 7. Patients whom the Investigator deems clinical trial participation is not in their best interest. B. Burn patients specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (All Types/Grades) Within a Time Frame up to 24 Hours Following the Transfusion. | 24 hours | 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 |
| Number of Participants Who Experienced an Adverse Event (AE) (All Types/Grades) Overall up to 7 Days (+/-1 Day) After the Transfusion. | 7 days (+/-1 day) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Calculation of the Hemoglobin Increment After Transfusion Corrected for Patient Blood Volume and Hemoglobin Dose | 28 days | 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. |
| Evaluation of AEs From Enrollment, up to Prior to the Subsequent Transfusion or up to Day 28, Whichever Occurs First | 28 days | Number of AEs that occur from enrollment, up to prior to the subsequent transfusion or up to Day 28, whichever occurs first |
| Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | baseline up to 15 minutes post-transfusion. | Change in blood pressure (systolic; mmHg) from baseline up to 15 minutes post-transfusion. |
| Evolution of the Hemoglobin Level Before and After the Transfusion. | pre-transfusion to up to 30 minutes post-transfusion | The difference in measured hemoglobin (grams/dL) between pre-transfusion and up to 30 minutes post-transfusion. |
| Evaluation of Subject's SO2 Level Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | baseline to up to 15 minutes post-transfusion | Change in the amount of oxygen in the body (% S02 level), measured with a pulse oximeter, from baseline to up to 15 minutes post-transfusion. |
| Evaluation of Subject's Pulse Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | baseline to up to 15 minutes post-transfusion | Change in heart rate (beats per minute) from baseline to up to 15 minutes post-transfusion |
| Evaluation of Subject's Respiratory Rate Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | baseline to up to 15 minutes post-transfusion | Change in respiratory rate (breaths per minute) from baseline to up to 15 minutes post-transfusion. |
| Comparison of the Hemoglobin Level Before the Index Transfusion to That Prior to the Subsequent Transfusion | 28 days | 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. |
Countries
Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hematologic Malignancies 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.
Hypoxic Red Blood Cells: Hypoxic Red Blood Cells manufactured with the Hemanext ONE device- CPD/PAGGSM Red Blood Cells, Leukocytes Reduced, and O2/CO2 Reduced | 10 |
| Acute Burn 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.
Hypoxic Red Blood Cells: Hypoxic Red Blood Cells manufactured with the Hemanext ONE device- CPD/PAGGSM Red Blood Cells, Leukocytes Reduced, and O2/CO2 Reduced | 12 |
| Total | 22 |
Baseline characteristics
| Characteristic | Total | Hematologic Malignancies | Acute Burn |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 8 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 2 Participants | 10 Participants |
| Age, Continuous | 59.8 years STANDARD_DEVIATION 21.08 | 72.0 years STANDARD_DEVIATION 16.41 | 49.6 years STANDARD_DEVIATION 19.46 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 10 Participants | 11 Participants |
| Region of Enrollment Norway | 22 participants | 10 participants | 12 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 18 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 12 |
| other Total, other adverse events | 4 / 10 | 6 / 12 |
| serious Total, serious adverse events | 0 / 10 | 1 / 12 |
Outcome results
Primary
Number of Participants Who Experienced an Adverse Event (AE) (All Types/Grades) 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
Time frame: 7 days (+/-1 day)
Population: Participants in the Safety analysis set. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hematologic Malignancies | Number of Participants Who Experienced an Adverse Event (AE) (All Types/Grades) Overall up to 7 Days (+/-1 Day) After the Transfusion. | 4 Participants |
| Acute Burn | Number of Participants Who Experienced an Adverse Event (AE) (All Types/Grades) Overall up to 7 Days (+/-1 Day) After the Transfusion. | 7 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (All Types/Grades) Within a Time Frame up to 24 Hours Following 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
Time frame: 24 hours
Population: Participants in the Safety analysis set who experienced an adverse event (all types/grades) within a time frame up to 24 hours following transfusion. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hematologic Malignancies | Number of Participants Who Experienced an Adverse Event (All Types/Grades) Within a Time Frame up to 24 Hours Following the Transfusion. | 2 Participants |
| Acute Burn | Number of Participants Who Experienced an Adverse Event (All Types/Grades) Within a Time Frame up to 24 Hours Following the Transfusion. | 3 Participants |
Secondary
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.
Time frame: 28 days
Population: Outcome not analyzed. The reason for this change is that it was not possible to calculate the hemoglobin increment from the collected data. Patient HgB results were collected pre and post transfusion. However, total HgB transfused (i.e. how much HgB was present in RBC units) was not assessed. This missing variable is required to complete the HgB Increment calculation, which prevented us from completing the calculation in order to report adjusted hemoglobin increment.
Secondary
Comparison of the Hemoglobin Level Before the Index Transfusion to That Prior to the Subsequent Transfusion
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.
Time frame: 28 days
Population: Safety analysis set. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Comparison of the Hemoglobin Level Before the Index Transfusion to That Prior to the Subsequent Transfusion | 0.21 g/dL | Standard Deviation 1.177 |
| Acute Burn | Comparison of the Hemoglobin Level Before the Index Transfusion to That Prior to the Subsequent Transfusion | 0.84 g/dL | Standard Deviation 2.065 |
Secondary
Evaluation of AEs From Enrollment, up to Prior to the Subsequent Transfusion or up to Day 28, Whichever Occurs First
Number of AEs that occur from enrollment, up to prior to the subsequent transfusion or up to Day 28, whichever occurs first
Time frame: 28 days
Population: Safety analysis set. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematologic Malignancies | Evaluation of AEs From Enrollment, up to Prior to the Subsequent Transfusion or up to Day 28, Whichever Occurs First | 4 adverse event |
| Acute Burn | Evaluation of AEs From Enrollment, up to Prior to the Subsequent Transfusion or up to Day 28, Whichever Occurs First | 7 adverse event |
Secondary
Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion
Change in blood pressure (systolic; mmHg) from baseline up to 15 minutes post-transfusion.
Time frame: baseline up to 15 minutes post-transfusion.
Population: Safety analysis set. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | -4.56 mmHg | Standard Deviation 6.521 |
| Acute Burn | Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | -3.40 mmHg | Standard Deviation 23.996 |
Secondary
Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion
Change in blood pressure (diastolic; mmHg) from baseline up to 15 minutes post-transfusion.
Time frame: baseline up to 15 minutes post-transfusion.
Population: Safety analysis set. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | -0.44 mmHg | Standard Deviation 7.333 |
| Acute Burn | Evaluation of Subject's Blood Pressure Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | 1.90 mmHg | Standard Deviation 9.219 |
Secondary
Evaluation of Subject's Pulse Over the Course of the Transfusion and up to 15 Minutes Post-transfusion
Change in heart rate (beats per minute) from baseline to up to 15 minutes post-transfusion
Time frame: baseline to up to 15 minutes post-transfusion
Population: Safety analysis set. Participants who did not receive a transfusion were not included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Evaluation of Subject's Pulse Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | -3.33 beats/min | Standard Deviation 6.144 |
| Acute Burn | Evaluation of Subject's Pulse Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | 5.40 beats/min | Standard Deviation 16.263 |
Secondary
Evaluation of Subject's Respiratory Rate Over the Course of the Transfusion and up to 15 Minutes Post-transfusion
Change in respiratory rate (breaths per minute) from baseline to up to 15 minutes post-transfusion.
Time frame: baseline to up to 15 minutes post-transfusion
Population: Safety analysis set. Participants who did not receive a transfusion were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Evaluation of Subject's Respiratory Rate Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | 0.00 breaths/min | Standard Deviation 2.062 |
| Acute Burn | Evaluation of Subject's Respiratory Rate Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | -1.10 breaths/min | Standard Deviation 2.846 |
Secondary
Evaluation of Subject's SO2 Level Over the Course of the Transfusion and up to 15 Minutes Post-transfusion
Change in the amount of oxygen in the body (% S02 level), measured with a pulse oximeter, from baseline to up to 15 minutes post-transfusion.
Time frame: baseline to up to 15 minutes post-transfusion
Population: Safety analysis set. Participants who did not receive a transfusion were not included in in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Evaluation of Subject's SO2 Level Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | 0.22 % O2 saturation | Standard Deviation 1.856 |
| Acute Burn | Evaluation of Subject's SO2 Level Over the Course of the Transfusion and up to 15 Minutes Post-transfusion | 0.00 % O2 saturation | Standard Deviation 1.633 |
Secondary
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.
Time frame: pre-transfusion to up to 30 minutes post-transfusion
Population: Safety analysis set. Participants who did not receive a transfusion were not included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Malignancies | Evolution of the Hemoglobin Level Before and After the Transfusion. | 1.20 g/dL | Standard Deviation 0.494 |
| Acute Burn | Evolution of the Hemoglobin Level Before and After the Transfusion. | 0.25 g/dL | Standard Deviation 0.981 |