Healthy Volunteers
Conditions
Keywords
Healthy Adults
Brief summary
This study sought to verify that the in vitro quality (functional assays) of platelets collected on the Trima Accel system, Version 6.4, diluted in InterSol Solution, and stored for 1, 5, and 7 days meet FDA requirements.
Detailed description
Platelets suspended in platelet additive solutions (PAS) have been collected and transfused in Europe for over 20 years. These PAS solutions outside of the United States (US) are not tied to an apheresis device; however in the US, PAS solutions have traditionally been linked to a corresponding apheresis device. Currently in the US, there are two solutions approved by the Food and Drug Administration (FDA) as a PAS for the replacement of 65% plasma in platelet components. Isoplate Solution is approved for use with the Trima Accel® Automated Blood Collection System (Trima Accel System) and InterSol Solution is approved for use with the Amicus Separator System. This study is designed to provide blood centers with the option to use either Isoplate or InterSol when collecting platelets for use with PAS. Terumo BCT is pursuing approval for InterSol Solution in combination with the Trima Accel System. This is a randomized, paired, prospective, open-label, multi-center study. Up to 120 healthy adult subjects will be enrolled in this study to ensure 60 paired evaluable data points across two Investigational Sites. Evaluable is defined as two completed platelet products with 100mL plasma that do not meet any of the protocol analysis exclusion criteria. The additional platelet donors account for screen failures, incomplete procedures, and protocol exclusions. Two units of platelets will be collected from each subject: one Test unit collected as a hyperconcentrated platelet product with 100 mL of concurrent plasma and one Control unit of platelets in plasma collected according to standard procedure. The Test unit will be suspended in 65% Intersol/35% plasma immediately after collection; the Control unit will be maintained in 100% plasma. Eligible donors who have signed an informed consent will be enrolled. Randomization will occur in a ratio of 1:1 to one of the following Treatment Arms: Arm A: Collection of one Test unit followed by collection of one Control unit Arm B: Collection of one Control unit followed by collection of one Test unit The standard apheresis platelet units collected in the Control arm will mirror the hyperconcentrated platelet units in the Test arm in terms of yield and final concentration. SUBJECT PROCEDURES Screening can be performed within 30 days of the apheresis procedure or combined with the first Apheresis Visit. The following evaluations will be performed: 1. Informed consent will be obtained prior to initiating any study specific procedures 2. Eligibility will be confirmed 3. Demographics (age, gender, ethnic origin), height, and weight 4. Complete blood count (CBC) for hemoglobin and platelet count on subjects new to the Investigative Site that do not have historical hemoglobin and/or platelet count measurements Apheresis Visit The following procedures will be performed at both the first and second Apheresis Visits: 1. Eligibility will be confirmed 2. Finger stick hemoglobin 3. First apheresis procedure will be performed Subject will return to the Site in 6 to 8 days following the first apheresis collection for the second apheresis collection. This will conclude the subject's participation. Apheresis procedures will be run according to the instructions and precautions described in the commercially available Trima Accel Operator's Manual for use with Version 6.4. The Investigator or designee will perform the venipuncture, monitor the subject during the collection, assess and provide any interventions for adverse effects, remove the needle, dress the puncture site and monitor subject through recovery. The following will be documented: 1. Trima Procedure details 2. Adverse events 3. Medications to treat AEs 4. Device deficiencies
Interventions
DEVICEPlatelets stored in InterSol
A platelet apheresis procedure involves connecting the blood in the donor's vein through tubing to a machine that separates the blood components. After the separation, the desired component of the blood is removed (platelets and plasma), while the remainder of the blood components are reinfused back into the patient. To prevent clotting, an anticoagulant (ACDA) is used throughout the procedure. Following each blood collection, Platelet Additive Solution (PAS), InterSol, will be added to the platelet product to prepare the final product for 7 day storage. The entire procedure is painless and should take 90 to 120 minutes and the subjects will have two collections within 6-8 days of each other.
DEVICEPlatelets stored in Plasma
A platelet apheresis procedure involves connecting the blood in the donor's vein through tubing to a machine that separates the blood components. After the separation, the desired component of the blood is removed (platelets and plasma), while the remainder of the blood components are reinfused back into the patient. To prevent clotting, an anticoagulant (ACDA) is used throughout the procedure. During the collection, plasma collected from the donor will be added to the platelet product to prepare the final product for 7 day storage. The entire procedure is painless and should take 90 to 120 minutes and the subjects will have two collections within 6-8 days of each other.
Sponsors
Terumo BCT
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age 18 years of age or older * Meet the inclusion criteria defined by the Investigational Site for an apheresis double platelet with plasma collection on the Trima Accel System. These criteria are based on American Association of Blood Banks (AABB) standards. Note: Subjects who are deferred from volunteer community donations because of travel restrictions, piercings or tattoos may participate in the study.
Exclusion criteria
* None.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pH of Platelets at Day 5 | Day 5 | The primary endpoint for this study is pH of platelets stored in InterSol at Day 5. The FDA acceptance criteria for pH is 95% of products have pH \>6.2 at 22 degrees C with 95% confidence interval. A sample size of 60 subjects was chosen for the study to meet the acceptance criteria with 0 failures out of 60 Test products. |
| pH of Platelets at Day 7 | Day 7 | The primary endpoint for this study is pH of platelets stored in InterSol at Day 7. The FDA acceptance criteria for pH is 95% of products have pH \>6.2 at 22 degrees C with 95% confidence interval. A sample size of 60 subjects was chosen for the study to meet the acceptance criteria with 0 failures out of 60 Test products. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Platelets Activated as Measured by P-selectin | Day 5 | Flow cytometric detection of platelet P-selectin expression (Units: %). Lower value is considered to indicate better platelet quality. |
| Percent of Extent of Shape Change | Day 5 | Measures the proportion of platelets that have a discoid morphology (Units: %). Higher value is considered to indicate better platelet quality. |
| Percent of Platelets Exhibiting Hypotonic Shock Response | Day 5 | Measures the ability of platelets to recover their volume after being exposed to a hypotonic environment (Units: % Recovery). Higher value is considered to indicate better platelet quality. |
| Platelet Morphology | Day 5 | Quantifies (via phase-contrast light microscopy) the morphological changes of platelets coincident with the full range of platelet activation profile (Units: Kunicki score; Range is 0 to 400). Higher values represent healthier platelets. |
Countries
United States
Participant flow
Pre-assignment details
87 volunteers signed consent and were enrolled in the study, but 2 were screen fails and therefore did not participate in the study
Participants by arm
| Arm | Count |
|---|---|
| InterSol First, Then Plasma Platelets collected in InterSol, then platelets collected in plasma | 44 |
| Plasma First, Then InterSol Platelets collected in plasma, then platelets collected in InterSol | 41 |
| Total | 85 |
Baseline characteristics
| Characteristic | Total | InterSol First, Then Plasma | Plasma First, Then InterSol |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 3 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 78 Participants | 41 Participants | 37 Participants |
| Age, Continuous | 42.1 years STANDARD_DEVIATION 14.49 | 40.9 years STANDARD_DEVIATION 14.1 | 43.3 years STANDARD_DEVIATION 14.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants | 43 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 69.0 inches STANDARD_DEVIATION 3.3 | 69.5 inches STANDARD_DEVIATION 3.12 | 68.5 inches STANDARD_DEVIATION 3.43 |
| Region of Enrollment United States | 85 participants | 44 participants | 41 participants |
| Sex: Female, Male Female | 28 Participants | 15 Participants | 13 Participants |
| Sex: Female, Male Male | 57 Participants | 29 Participants | 28 Participants |
| Total Blood Volume (TBV) | 5280.0 mL STANDARD_DEVIATION 767.04 | 5380.1 mL STANDARD_DEVIATION 770.93 | 5172.5 mL STANDARD_DEVIATION 757.45 |
| Weight | 193.4 lbs STANDARD_DEVIATION 32.87 | 197.9 lbs STANDARD_DEVIATION 34.38 | 188.7 lbs STANDARD_DEVIATION 30.87 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 77 |
| other Total, other adverse events | 9 / 82 | 2 / 77 |
| serious Total, serious adverse events | 0 / 82 | 0 / 77 |
Outcome results
Primary
pH of Platelets at Day 5
The primary endpoint for this study is pH of platelets stored in InterSol at Day 5. The FDA acceptance criteria for pH is 95% of products have pH \>6.2 at 22 degrees C with 95% confidence interval. A sample size of 60 subjects was chosen for the study to meet the acceptance criteria with 0 failures out of 60 Test products.
Time frame: Day 5
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | pH of Platelets at Day 5 | 7.184 pH | Standard Deviation 0.0718 |
| Control Platelets Collected and Stored in Plasma | pH of Platelets at Day 5 | 7.414 pH | Standard Deviation 0.0975 |
Comparison: A success is defined as pH22°C at Day 5 and Day 7 being at least 6.2. A one-sided 95% lower confidence limit will be used to assess the proportion of successes at Day 5 and Day 7. If the lower limit of the one-sided 95% confidence interval exceeds 0.95, the Test product will meet the FDA acceptance criteria.Exact Binomial Confidence Interval
Primary
pH of Platelets at Day 7
The primary endpoint for this study is pH of platelets stored in InterSol at Day 7. The FDA acceptance criteria for pH is 95% of products have pH \>6.2 at 22 degrees C with 95% confidence interval. A sample size of 60 subjects was chosen for the study to meet the acceptance criteria with 0 failures out of 60 Test products.
Time frame: Day 7
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | pH of Platelets at Day 7 | 7.152 pH | Standard Deviation 0.0855 |
| Control Platelets Collected and Stored in Plasma | pH of Platelets at Day 7 | 7.335 pH | Standard Deviation 0.1313 |
Comparison: A success is defined as pH22°C at Day 5 and Day 7 being at least 6.2. A one-sided 95% lower confidence limit will be used to assess the proportion of successes at Day 5 and Day 7. If the lower limit of the one-sided 95% confidence interval exceeds 0.95, the Test product will meet the FDA acceptance criteria.Exact Bionomial Confidence Interval
Secondary
Percent of Extent of Shape Change
Measures the proportion of platelets that have a discoid morphology (Units: %). Higher value is considered to indicate better platelet quality. Higher value is considered to indicate better platelet quality.
Time frame: Day 7
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Percent of Extent of Shape Change | 19.328 % of extent of shape change | Standard Deviation 6.1433 |
| Control Platelets Collected and Stored in Plasma | Percent of Extent of Shape Change | 27.962 % of extent of shape change | Standard Deviation 5.4495 |
Comparison: The null hypothesis is that ESC's mean difference, Test - 0.8 \* Control, is less than or equal to 0, and the alternative is that the mean difference is greater than 0.
Secondary
Percent of Extent of Shape Change
Measures the proportion of platelets that have a discoid morphology (Units: %). Higher value is considered to indicate better platelet quality.
Time frame: Day 5
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Percent of Extent of Shape Change | 24.109 % extent of shape change | Standard Deviation 5.9968 |
| Control Platelets Collected and Stored in Plasma | Percent of Extent of Shape Change | 30.658 % extent of shape change | Standard Deviation 5.1498 |
Comparison: The null hypothesis is that ESC's mean difference, Test - 0.8 \* Control, is less than or equal to 0, and the alternative is that the mean difference is greater than 0.
Secondary
Percent of Platelets Activated as Measured by P-selectin
Flow cytometric detection of platelet P-selectin expression (Units: %). Lower value is considered to indicate better platelet quality.
Time frame: Day 7
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Percent of Platelets Activated as Measured by P-selectin | 29.392 Percent of Platelets Activated | Standard Deviation 8.0418 |
| Control Platelets Collected and Stored in Plasma | Percent of Platelets Activated as Measured by P-selectin | 14.232 Percent of Platelets Activated | Standard Deviation 6.4316 |
Comparison: The null hypothesis is that P-selection's mean difference, Test - 1.25 \* Control, is greater or equal to 0, and the alternative is that the mean difference is less than 0.
Secondary
Percent of Platelets Activated as Measured by P-selectin
Flow cytometric detection of platelet P-selectin expression (Units: %). Lower value is considered to indicate better platelet quality.
Time frame: Day 5
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Percent of Platelets Activated as Measured by P-selectin | 26.324 Percent of Platelets Activated | Standard Deviation 7.6052 |
| Control Platelets Collected and Stored in Plasma | Percent of Platelets Activated as Measured by P-selectin | 9.354 Percent of Platelets Activated | Standard Deviation 4.411 |
Comparison: The null hypothesis is that P-selectin's mean difference, Test - 1.25 \* Control, is greater than or equal to 0, and the alternative is that the mean difference is less than 0.
Secondary
Percent of Platelets Exhibiting Hypotonic Shock Response
Measures the ability of platelets to recover their volume after being exposed to a hypotonic environment (Units: % Recovery). Higher value is considered to indicate better platelet quality.
Time frame: Day 5
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Percent of Platelets Exhibiting Hypotonic Shock Response | 44.507 % of hypotonic shock response | Standard Deviation 8.4013 |
| Control Platelets Collected and Stored in Plasma | Percent of Platelets Exhibiting Hypotonic Shock Response | 56.467 % of hypotonic shock response | Standard Deviation 9.6924 |
Comparison: The null hypothesis is that HSR's mean difference, Test - 0.8 \* Control, is less than or equal to 0, and the alternative is that the mean difference is greater than 0.
Secondary
Percent of Platelets Exhibiting Hypotonic Shock Response
Measures the ability of platelets to recover their volume after being exposed to a hypotonic environment (Units: % Recovery). Higher value is considered to indicate better platelet quality.
Time frame: Day 7
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Percent of Platelets Exhibiting Hypotonic Shock Response | 37.038 % of hypotonic shock response | Standard Deviation 7.4719 |
| Control Platelets Collected and Stored in Plasma | Percent of Platelets Exhibiting Hypotonic Shock Response | 49.284 % of hypotonic shock response | Standard Deviation 11.4719 |
Comparison: The null hypothesis is that HSR's mean difference, Test - 0.8 \* Control, is less than or equal to 0, and the alternative is that the mean difference is greater than 0.
Secondary
Platelet Morphology
Quantifies (via phase-contrast light microscopy) the morphological changes of platelets coincident with the full range of platelet activation profile (Units: Kunicki score; Range is 0 to 400). Higher values represent healthier platelets.
Time frame: Day 7
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Platelet Morphology | 269.7 score on a scale | Standard Deviation 31.26 |
| Control Platelets Collected and Stored in Plasma | Platelet Morphology | 282.5 score on a scale | Standard Deviation 34.79 |
Comparison: The null hypothesis is that Morphology's mean difference, Test - 0.8 \* Control, is less than or equal to 0, and the alternative is that the mean difference is greater than 0.
Secondary
Platelet Morphology
Quantifies (via phase-contrast light microscopy) the morphological changes of platelets coincident with the full range of platelet activation profile (Units: Kunicki score; Range is 0 to 400). Higher values represent healthier platelets.
Time frame: Day 5
Population: The Full Analysis Set (FAS) was used to examine the primary and secondary endpoints.The FAS consisted of all products where the corresponding Test and Control values for the primary endpoint did not meet any of the protocol analysis exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Platelets Collected and Stored in InterSol | Platelet Morphology | 293.1 scores on a scale | Standard Deviation 31.76 |
| Control Platelets Collected and Stored in Plasma | Platelet Morphology | 308.7 scores on a scale | Standard Deviation 33.3 |
Comparison: The null hypothesis is that Morphology's mean difference, Test - 0.8 \* Control, is less than or equal to 0, and the alternative is that the mean difference is greater than 0.