Trial Outcomes & Findings for Efficacy and Safety of RBCs Derived From Mirasol-treated Whole Blood in Patients Requiring Chronic Transfusion (PRAISE) (NCT NCT03329404)

Results Overview

The Hb AUC is calculated using the trapezoidal method on normalized Hb. The normalization is accomplished by dividing all posttransfusion Hb values by the 15-minute posttransfusion Hb level. The ratio is expressed as a percentage. A natural log-transform of the observed normalized Hb AUC will be utilized.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

9 participants

Primary outcome timeframe

Crossover design with 2 treatment periods. Each period included a 50-day wash-in followed by 2 transfusion episodes for primary endpoint assessment. Expected participation was approximately 7-10 months, depending on the subject's transfusion schedule.

Results posted on

2024-02-14

Participant Flow

Nine subjects were enrolled and assigned into treatment arms. The first subject signed consent on 12 April 2018 and the last subject signed consent on 03 October 2018.

This was a crossover study, all 9 randomized subjects were to receive both Mirasol and Reference RBCs in either period 1 or 2. 4 subjects were randomized to the MIR/REF RBC treatment sequence and 5 subjects were randomized to the REF/MIR RBC sequence. 4 subjects completed period 1, no subjects completed period 2 due to study suspension. Because no subjects completed the study, the primary endpoint was not evaluated and results are summarized by treatment type rather than treatment sequence.

Participant milestones

Participant milestones
Measure	Mirasol Red Blood Cells (MIR RBCs) Followed by Reference RBCs (REF RBCs) MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) Followed by Mirasol RBCs (MIR RBCs) REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs were per site standard inventory. MIR RBCs: RBCs were derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Overall Study STARTED	4	5
Overall Study COMPLETED	3	1
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Mirasol Red Blood Cells (MIR RBCs) Followed by Reference RBCs (REF RBCs) MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) Followed by Mirasol RBCs (MIR RBCs) REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs were per site standard inventory. MIR RBCs: RBCs were derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Overall Study The study was suspended.	1	4

Baseline Characteristics

Efficacy and Safety of RBCs Derived From Mirasol-treated Whole Blood in Patients Requiring Chronic Transfusion (PRAISE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mirasol Red Blood Cells (MIR RBCs)/Reference Red Blood Cells (REF RBCs) Treatment Sequence n=4 Participants MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs)/Mirasol Red Blood Cells (MIR RBCs) Treatment Sequence n=5 Participants REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs were per site standard inventory. MIR RBCs: RBCs were derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Crossover design with 2 treatment periods. Each period included a 50-day wash-in followed by 2 transfusion episodes for primary endpoint assessment. Expected participation was approximately 7-10 months, depending on the subject's transfusion schedule.

Population: The Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. Ninety-seven subjects were planned to be enrolled however 9 were randomized. None of the 9 randomized subjects completed the sequence arms and met the per protocol criteria and as such the primary endpoint was not collected.

The Hb AUC is calculated using the trapezoidal method on normalized Hb. The normalization is accomplished by dividing all posttransfusion Hb values by the 15-minute posttransfusion Hb level. The ratio is expressed as a percentage. A natural log-transform of the observed normalized Hb AUC will be utilized.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Endpoint assessments was evaluated at 15 min Post Transfusion, 1 Day Post Transfusion, 7 Day Post Transfusion, and End of Transfusion Episode.

Population: The Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. Ninety-seven subjects were planned to be enrolled however 9 were randomized. None of the 9 randomized subjects completed the sequence arms and met the per protocol criteria and as such the secondary endpoint was not analyzed as planned in the Statistical Analysis Plan. The limited data collected was analyzed per intervention, not by sequence.

(post-transfusion Hb - pre-transfusion Hb)/Hb transfused\]/RBC volume in subject at pre-transfusion

Outcome measures

Outcome measures
Measure	Mirasol Red Blood Cells (MIR RBCs) n=4 Participants MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) n=8 Participants REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Hb Increment 15 minute Post-Transfusion	0.000299 delta g/dl per mL RBC transfused Standard Deviation 0.000422	0.000288 delta g/dl per mL RBC transfused Standard Deviation 0.000400
Hb Increment 1 Day Post-Transfusion	0.000297 delta g/dl per mL RBC transfused Standard Deviation 0.000486	0.000362 delta g/dl per mL RBC transfused Standard Deviation 0.000330
Hb Increment 7 Day Post-Transfusion	0.000173 delta g/dl per mL RBC transfused Standard Deviation 0.000287	0.000149 delta g/dl per mL RBC transfused Standard Deviation 0.000181
Hb Increment End of Transfusion Interval	0.000014 delta g/dl per mL RBC transfused Standard Deviation 0.000159	-0.000041 delta g/dl per mL RBC transfused Standard Deviation 0.0000999

SECONDARY outcome

Timeframe: An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment

Population: The SAP was not executed for this study as the study was stopped prematurely. None of the 9 randomized subjects completed the sequence arms and met the per protocol criteria. Post-hoc analysis was performed by intervention, not by the randomized sequence arm. Of the 9 randomized subjects, 1 subject did not enter either treatment period.There were 4 MIR treatment periods and 8 REF treatment periods.

Actual Hb level post-transfusion (15 min)

Outcome measures

Outcome measures
Measure	Mirasol Red Blood Cells (MIR RBCs) n=4 Participants MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) n=8 Participants REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Actual Hb Level Post-transfusion (15 Min)	11.19 grams/dL Standard Deviation 1.44	11.49 grams/dL Standard Deviation 0.65

OTHER_PRE_SPECIFIED outcome

Timeframe: An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment.

Population: The Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. Ninety-seven subjects were planned to be enrolled however 9 were randomized. None of the 9 randomized subjects completed the sequence arms and met the per protocol criteria and as such the secondary endpoint was not analyzed according to the Statistical Analysis Plan. The limited data collected was analyzed per intervention, not by sequence.

Percentage decline in post-transfusion Hb level

Outcome measures

Outcome measures
Measure	Mirasol Red Blood Cells (MIR RBCs) n=4 Participants MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) n=8 Participants REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Percentage Decline in Post-transfusion Hb Level	-4.256 percent change Standard Deviation 5.367	-3.249 percent change Standard Deviation 5.568

OTHER_PRE_SPECIFIED outcome

Timeframe: An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment

Population: The Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. Ninety-seven subjects were planned to be enrolled however 9 were randomized. None of the 9 randomized subjects completed the sequence arms and met the per protocol criteria and as such the secondary endpoint was not analyzed as planned in the Statistical Analysis Plan. The limited data collected was analyzed per intervention, not by sequence.

volume x Hb/unit

Outcome measures

Outcome measures
Measure	Mirasol Red Blood Cells (MIR RBCs) n=4 Participants MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) n=8 Participants REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
RBC Mass Infused	1445.796 grams Standard Deviation 33.622	107.039 grams Standard Deviation 29.583

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study transfusion

Population: Safety Set. The Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. Of the 97 subjects planned to be enrolled, only 9 subjects were randomized and none completed the sequence arms. Of the 9 subjects, one did not enter either treatment period. The limited data collected was analyzed per intervention, not by sequence.

Antibody screening was performed in a total of 8 (100%) subjects in the SS at a total of 97 intervals (Pre-Transfusion, 7 Days Post-Transfusion or End of Study Treatment Follow-up Visit).

Outcome measures

Outcome measures
Measure	Mirasol Red Blood Cells (MIR RBCs) n=43 antibody screen test MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) n=54 antibody screen test REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Number of Antibody Screening Test With Confirmed Specificity to RBCs Derived From Mirasol-treated WB	0 antibody screen test	3 antibody screen test

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study.

Population: Safety Set. The Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. Of the 97 subjects planned to be enrolled, only 9 subjects were randomized and none completed the sequence arms. Of the 9 subjects, one did not enter either treatment period. The limited data collected was analyzed by sequence.

The highest of three different normalized background ratio (NBG) cut-offs was used to quantify positivity for Class I HLA antibodies prior to transfusion as it was used to identify conversion from HLA antibody negative prior to transfusion to positivity after transfusion(s) within the applicable treatment group.

Outcome measures

Outcome measures
Measure	Mirasol Red Blood Cells (MIR RBCs) n=4 Participants MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	Reference Red Blood Cells (REF RBCs) n=4 Participants REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Number of Participants With Human Leukocyte Antigen (HLA) Alloimmunization Post Transfusion	1 Participants	0 Participants

Adverse Events

Mirasol Red Blood Cells (MIR RBCs)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Reference Red Blood Cells (REF RBCs)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Mirasol Red Blood Cells (MIR RBCs) n=4 participants at risk MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, leukoreduced, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.	Reference Red Blood Cells (REF RBCs) n=8 participants at risk REF RBCs: Leukoreduced apheresis RBCs or whole blood-derived RBCs were per site standard inventory.
Blood and lymphatic system disorders Thrombocytosis	25.0% 1/4 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	0.00% 0/8 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Metabolism and nutrition disorders Hypoglycemia	25.0% 1/4 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	0.00% 0/8 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	12.5% 1/8 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Investigations Aspartate aminotransferase increased	0.00% 0/4 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	12.5% 1/8 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Investigations Alanine aminotransferase increased	0.00% 0/4 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	12.5% 1/8 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/4 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	12.5% 1/8 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.	12.5% 1/8 • Number of events 1 • 8 months This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.

Additional Information

Robert Cortes, Jr. MD

Terumo Blood and Cell Technologies

Phone: +1.303.231.4353

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60