Inactivation of Whole Blood With Mirasol (IMPROVEII)

• ClinicalTrials.gov Identifier: NCT01907906
• Recruitment Status: Completed
• First Posted: July 25, 2013
• Results First Posted: July 27, 2015
• Last Update Posted: August 18, 2015
• Sponsor: Terumo BCTbio
• Collaborator: U.S. Army Medical Research and Development Command
• Information provided by (Responsible Party): Terumo BCTbio

Study Description

Brief Summary:

The purpose of this study is to evaluate radiolabeled recovery and survival of autologous red blood cells (RBC), derived from Mirasol-treated fresh whole blood (WB), stored as leukoreduced packed RBC (LR-pRBC), and re-infused in healthy adult subjects

Condition or disease	Intervention/treatment	Phase
Focus of Study: Radiolabel Recovery and Survival of RBCs	Device: Mirasol System for Whole Blood	Phase 1

Detailed Description:

This is a feasibility level study conducted to assess the recovery and survival of autologous, radiolabeled leukoreduced packed red blood cells (LR-pRBC) derived from fresh whole blood (WB) units that have been treated with the Mirasol System for Whole Blood (Mirasol System) and stored for 21 days at 1-6°C.1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Inactivation of Whole Blood With Mirasol : Performance in Red Blood Cells in Healthy Volunteers
• Study Start Date: June 2013
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: Mirasol-treated WB then untreated WB; Screening Period (14 days); Treatment Period 1 (49 days): Donation of WB treated with Mirasol System for Whole Blood on Day 0, LR-pRBCs manufactured & stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49); WB Donation Deferral Period (35-49 days); Treatment Period 2 (49 days): Donation of WB, UNTREATED on Day 0, LR-pRBCs manufactured & stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49) Study Exit on Treatment Period 2, Day 49	Device: Mirasol System for Whole Blood; LR-pRBC units derived from WB will be treated with the Mirasol System. Treatment with the Mirasol System requires riboflavin to be mixed into the whole blood unit, which is then exposed to ultra violet (UV) light for a period of time; approximately an hour.; Other Name: Pathogen Reduction Technology
Experimental: Arm 2: Untreated WB then Mirasol-treated WB; Screening Period (14 days); Treatment Period 1 (49 days): Donation of WB, UNTREATED on Day 0, LR-pRBCs manufactured & stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49); WB Donation Deferral Period (35-49 days); Treatment Period 2 (49 days): Donation of WB treated with Mirasol System for Whole Blood on Day 0, LR-pRBCs manufactured & stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49) Study Exit on Treatment Period 2, Day 49	Device: Mirasol System for Whole Blood; LR-pRBC units derived from WB will be treated with the Mirasol System. Treatment with the Mirasol System requires riboflavin to be mixed into the whole blood unit, which is then exposed to ultra violet (UV) light for a period of time; approximately an hour.; Other Name: Pathogen Reduction Technology

Outcome Measures

Primary Outcome Measures :

1. Red Blood Cell (RBC) 24-Hour Recovery [ Time Frame: 24 hours ]

   To evaluate, as per FDA criteria, the 24-hour post transfusion RBC recovery in healthy adult subjects of leuko-reduced packed red blood cells (LR-pRBC) that have been derived from Mirasol-treated fresh WB units and stored at 1 to 6°C for 21 days.

   24-hour RBC Recovery is a measure of the % of RBCs that are still functioning 24 hours after they have been reinfused back into the donor following storage over 21 days.

Secondary Outcome Measures :

1. Red Blood Cell (RBC) Survival by Product [ Time Frame: 28 days ]
   Assessment of linear & exponential RBC survival and half-life (T50) over 28 days for RBCs derived from Mirasol-treated WB versus RBCs derived from untreated WB.
2. Area Under the Curve (AUC) of Red Blood Cell (RBC) Survival [ Time Frame: 28 days ]
   Assessment of AUC of RBC survival over 28 days for RBCs derived from Mirasol-treated Whole Blood (WB) versus RBCs derived from untreated WB.
3. Spearman's Correlation Coefficients: 24-Hour Red Blood Cell (RBC) Recovery (%) With Hemolysis (%) [ Time Frame: 24 hours ]
   Spearman's Correlation Coefficients comparing 24-Hour RBC Recovery (%) with Hemolysis (%) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
4. Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) With Adenosine Triphosphate (ATP) (µmol/g Hgb) [ Time Frame: 24 hours ]
   Spearman's Correlation Coefficients comparing 24-Hour RBC Recovery (%) with ATP (µmol/g Hgb) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
5. Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) pCO2 (mmHg at 37° C) [ Time Frame: 24 hours ]
   Spearman's Correlation Coefficients comparing 24-Hour RBC Recovery (%) with pCO2 (mmHg at 37° C) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
6. Spearman's Correlation Coefficients: Linear T50 (Days) With Hemolysis (%) [ Time Frame: 28 days ]
   Spearman's Correlation Coefficients comparing Linear T50 (Days) with each of Hemolysis (%) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
7. Spearman's Correlation Coefficients: Linear T50 (Days) With Adenosine Triphosphate (ATP) (µmol/g Hgb) [ Time Frame: 28 days ]
   Spearman's Correlation Coefficients comparing Linear T50 (Days) with ATP (µmol/g Hgb) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
8. Spearman's Correlation Coefficients: Linear T50 (Days) With pCO2 (mmHg at 37° C) [ Time Frame: 28 days ]
   Spearman's Correlation Coefficients comparing Linear T50 (Days) with pCO2 (mmHg at 37° C) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
9. Neoantigenicity - Day 21 Direct Antigen Test (DAT) [ Time Frame: Day 21 ]
   DAT testing of Red Blood Cells (RBCs) via Anti-immunoglobulin G (Anti-IgG) and Anti Complement Component 3 (Anti-C3) as derived from Mirasol-treated whole blood (WB) versus untreated WB conducted on Day 21 of both Treatment Periods 1 and 2. Number of positive results (indicating a new antigen formation) were recorded.
10. Neoantigenicity - Day 21 Indirect Antigen Test (IAT) [ Time Frame: Day 21 of Treatment Periods 1 and 2 ]
    Day 21 IAT testing of RBCs via LISS-15, Anti-IgG and C3 as derived from Mirasol-treated WB versus untreated WB. Number of positive results (indicating antibody formation to a new antigen) were recorded.
11. Neoantigenicity - Day 42 Direct Antigen Test (DAT) [ Time Frame: Day 42 of Treatment Periods 1 and 2 ]
    DAT testing of RBCs via Anti-IgG and Anti-C3 as derived from Mirasol-treated WB versus untreated WB. Number of positive results (indicating a new antigen formation) were recorded.
12. Neoantigenicity - Day 42 Indirect Antigen Test (IAT) [ Time Frame: Day 42 of Treatment Periods 1 and 2 ]
    IAT testing of RBCs via low ionic strength solution (LISS-15), Anti-IgG and C3 as derived from Mirasol-treated WB versus untreated WB. Number of positive results (indicating antibody formation to a new antigen) were recorded.
13. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%) [ Time Frame: Day 0 ]
14. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%) [ Time Frame: Day 21 ]
15. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP [ Time Frame: Day 0 ]
16. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP [ Time Frame: Day 21 ]
17. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count [ Time Frame: Day 0 ]
18. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count [ Time Frame: Day 21 ]
19. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin [ Time Frame: Day 0 ]
20. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin [ Time Frame: Day 21 ]
21. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C) [ Time Frame: Day 0 ]
22. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C) [ Time Frame: Day 21 ]
23. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C) [ Time Frame: Day 0 ]
24. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C) [ Time Frame: Day 21 ]
25. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium [ Time Frame: Day 0 ]
26. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium [ Time Frame: Day 21 ]
27. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose [ Time Frame: Day 0 ]
28. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose [ Time Frame: Day 21 ]
29. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate [ Time Frame: Day 0 ]
30. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate [ Time Frame: Day 21 ]
31. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb [ Time Frame: Day 0 ]
32. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb [ Time Frame: Day 21 ]
33. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG) [ Time Frame: Day 0 ]
34. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG) [ Time Frame: Day 21 ]
35. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%) [ Time Frame: Day 0 ]
36. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%) [ Time Frame: Day 21 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Eligible whole blood donor
• Age ≥ 18 years, of either sex
• Able to commit to the study follow-up schedule
• Subjects must have adequate bilateral antecubital venous access for WB collection and follow-up blood draws
• Negative screening test panel for infectious diseases
• Subjects of child-bearing potential (female or male) must agree to use effective contraceptive during the course of the study per site guidelines
• Subjects must agree to report adverse events (AEs) during the required reporting period
• Negative direct antiglobulin test (DAT) with subject's RBC
• Negative indirect antiglobulin test (IAT) with subject's serum

Inclusion for radiolabeled reinfusion of LR-pRBC on Day 21 (evaluated the day of, prior to, reinfusion):

• Maintenance of healthy status
• Negative direct antiglobulin test (DAT) with subject's RBC (fresh)
• Negative indirect antiglobulin test (IAT) with subject's serum (fresh) versus autologous stored LR-pRBC
• Negative serum or urine pregnancy test in females

Exclusion Criteria:

• Any serious medical illness and/or therapy, including: abnormal bleeding episodes, clotting or bleeding disorder, evidence of anemia, myocardial infarction, uncontrolled hypertension, heart disease, surgery with bleeding complications, epilepsy or any major surgery (with general or spinal anesthesia) within the last 6 months
• Pregnant or nursing females; For women of childbearing potential, negative serum or urine pregnancy tests at the time of WB donation and before the reinfusion are required
• Unable to give informed consent
• Participation currently, or within the last 12 months, in another investigational trial that would potentially interfere with the analysis of this investigation (e.g., pharmaceutical)
• Have received an accumulated radiation dose that would exclude them from the study according to the local radiation safety limits established by each institution
• Inability to comply with the protocol in the opinion of the investigator

Contacts and Locations

Locations

United States, Ohio

Hoxworth Blood Center

Cincinnati, Ohio, United States, 45267

United States, Washington

Puget Sound Blood Center

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Terumo BCTbio

U.S. Army Medical Research and Development Command

Investigators

• Study Director: Raymond P Goodrich, PhD; TerumoBCT Biotechnologies

More Information

• Responsible Party: Terumo BCTbio
• ClinicalTrials.gov Identifier: NCT01907906
• Other Study ID Numbers: CTS-0080; ERMS#12308001 ( Other Grant/Funding Number: Department of Defense )
• First Posted: July 25, 2013
• Results First Posted: July 27, 2015
• Last Update Posted: August 18, 2015
• Last Verified: July 2015

Keywords provided by Terumo BCTbio:

Pathogen reduction technology