Hemophilia A
Conditions
Keywords
Hemophilia A (severe or moderately severe)
Brief summary
The purpose of this study is to compare the hemostatic efficacy and safety of continuous infusion versus intermittent bolus infusion in the peri- and post-operative setting, employing rAHF-PFM, a recombinant antihemophilic factor manufactured without added human or animal proteins, in previously treated patients with severe or moderately severe hemophilia A (baseline factor VIII level \<= 2% of normal) who are undergoing unilateral major orthopedic surgery that requires drain placement. The total study period per subject (from consent to study completion) will vary from approximately 9 to 26 weeks and will involve clinical and laboratory assessments.
Interventions
DRUGRecombinant Protein-Free Factor VIII (rAHF-PFM)
An initial loading dose will be administered intravenously over a period \<= 5 minutes (maximum of infusion rate of 10 mL/minute) within 60 minutes prior to surgery dose in order to maintain a minimum target FVIII level of at least 80% of normal. CI will start prior to surgery as soon as the loading dose has been administered, at a rate calculated according to a formula provided by the sponsor. All study product must be administered with a syringe pump running at an infusion rate according to the dosing regimen, but always \>= 0.4 mL/h.
Sponsors
Baxalta Innovations GmbH, now part of Shire
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The subject or the subject's legally authorized representative has provided signed informed consent. * The subject is within 18 to 70 years of age. * The subject has severe or moderately severe hemophilia A, defined by a baseline factor VIII level \<= 2% of normal, as tested at screening. A subset of 15 subjects per group must have baseline factor VIII levels \< 1% of normal. * The aPTT must be within the range of normal after administration of FVIII concentrate, as determined in the preoperative pharmacokinetic evaluation, or as documented in the medical history, if available. * The subject is scheduled to undergo an elective unilateral major orthopedic surgery that requires drain placement. * The subject was previously treated with factor VIII concentrate(s) for a minimum of at least 150 exposure days (as estimated by the investigator) prior to study entry. * Human immunodeficiency virus (HIV) positive subjects must be immunocompetent as determined with a CD4 count \>= 200 cells/mm³ (CD4 count at screening), but HIV negative subjects with a CD4 count \< 200 cells/mm³ qualify, if immunocompetency is documented. * The subject has a life expectancy of at least 28 days from the day of surgery.
Exclusion criteria
* The subject has a detectable factor VIII inhibitor at screening, with a titer \>= 0.4 BU (Nijmegen modification of the Bethesda assay) in the central laboratory. * The subject has a history of factor VIII inhibitors with a titer \>= 0.4 BU (by Nijmegen assay) or \>= 0.5 BU (by Bethesda assay) at any time prior to screening. * The subject is scheduled to undergo any other concurrent minor or major surgery during the course of the study. The placement of central venous lines and the performance of fine needle aspiration biopsies are permitted. * Excluding hemophilia-related physical impairments, the subject is assigned to NYHA class \>= III according to the New York Heart Association (NYHA). * The subject has an abnormal renal function (serum creatinine \> 1.5 mg/dL). * The subject has active hepatic disease (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] levels \> 5 times the upper limit of normal). * The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) \> 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices. * The subject has clinical and/or laboratory evidence of abnormal hemostasis from causes other than hemophilia A (e.g., late-stage chronic liver disease, immune thrombocytopenia purpura). * The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug other than anti-retroviral chemotherapy (e.g., alpha-interferon, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day). * The subject has a known hypersensitivity to mouse or hamster proteins. * The subject has received another investigational drug study within 30 days prior to screening and/or is scheduled to receive additional investigational drug during the course of the trial in the context of another investigational study. * The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | During the first postoperative 24 hours every 8 hours ± 30 minutes the drainage fluid was to be recorded.. | Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Unit of measure: Tera per Liter is the PRBC concentration in 10\^12 units per 1 liter of drainage fluid. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | From end of surgery (application of compressive dressing and release of tourniquet, if applicable) until drain removal (up to postoperative day 7). | The total blood loss for the postoperative period (from end of surgery until drain removal) was adjusted for the expected blood loss by applying a log-transformation of the blood loss data. The drainage volume was measured every 8 hours +/- 30 minutes during the first 24 hours. If the drainage continued beyond 24 hours, the PRBC volume and hemoglobin was to be measured cumulatively every 24 hours or whenever the drainage bottle was emptied and at the time of drain removal. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject for the first 24 hours postoperatively, and for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood |
| Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | Through Postoperative Day 7 | To simplify the results below: Bleeding episodes were reported for 4 subjects (3 subjects on bolus infusion: 2 in Stratum A and 1 in Stratum B, and 1 subject on continuous infusion/Stratum B). The 4 subjects had 1 bleeding episode each. No bleeding episodes were reported for Stratum C. |
| Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | During the first 24 postoperative hours blood loss was measured every 8 hours ± 30 minutes | Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject 1) for the intraoperative procedure (defined as the time period from incision to application of compressive dressing and release of tourniquet, if applicable), 2) for the first 24 hours postoperatively, and 3) for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood |
| Number of Adverse Events Related to the Administration of the Study Product. | From first study drug exposure until study completion/discontinuation (approximately 9-26 weeks per subject) | All AEs from the first study drug exposure until the study completion/discontinuation date were to be recorded. Each AE was to be evaluated by the investigator for causal relationship (i.e., unrelated, possibly related or probably related) to the study product. |
| Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation) | Throughout the study period of approximately 9-26 weeks per participant | Number of participants that developed Factor VIII inhibitory antibody during the study. |
| Number of Units of Packed Red Blood Cells Transfused | During the first postoperative 24 hours | — |
Countries
Austria, Belgium, France, Hungary, Italy, Netherlands, Norway, Poland, Portugal, Romania, Russia, Spain, Sweden, United States
Participant flow
Recruitment details
Enrollment was conducted at 22 clinical sites in 12 countries (US, Austria, Norway, France, Portugal, Netherlands, Spain, Russia, Romania, Hungary, Italy, Poland). Of 85 participants enrolled, 72 participants participated in a PK study in the preoperative period; 63 participants were then randomized to treatment by continuous or bolus infusion.
Pre-assignment details
Of 85 participants enrolled,15 were screen failures (2 after PK), 4 discontinued on the basis of the PK study in the preoperative period, 1 died, 1 was discontinued by physician decision (imprisonment), and 1 was discontinued per sponsor decision. Eventually, 63 participants were randomized to treatment by continuous (n=32) or bolus infusion (n=31)
Participants by arm
| Arm | Count |
|---|---|
| Bolus Infusion Bolus infusion of ADVATE (rAHF-PFM) | 31 |
| Continuous Infusion Continuous infusion of ADVATE (rAHF-PFM) | 32 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other, No surgery performed | 0 | 3 |
Baseline characteristics
| Characteristic | Bolus Infusion | Continuous Infusion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 32 Participants | 63 Participants |
| Age, Continuous | 38.6 Years STANDARD_DEVIATION 9.76 | 39.0 Years STANDARD_DEVIATION 11.52 | 38.8 Years STANDARD_DEVIATION 10.61 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 31 Participants | 32 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 31 | 20 / 32 | 2 / 9 |
| serious Total, serious adverse events | 3 / 31 | 6 / 32 | 1 / 9 |
Outcome results
Primary
Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI)
Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Unit of measure: Tera per Liter is the PRBC concentration in 10\^12 units per 1 liter of drainage fluid.
Time frame: During the first postoperative 24 hours every 8 hours ± 30 minutes the drainage fluid was to be recorded..
Population: All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bolus Infusion | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.632 Tera per Liter | Standard Deviation 0.971 |
| Continuous Infusion | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.383 Tera per Liter | Standard Deviation 0.632 |
| BI Stratum A | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.718 Tera per Liter | Standard Deviation 0.978 |
| BI Stratum B | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 2.855 Tera per Liter | Standard Deviation 1.732 |
| BI Stratum C | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.548 Tera per Liter | Standard Deviation 0.577 |
| CI Stratum A | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.345 Tera per Liter | Standard Deviation 0.616 |
| CI Stratum B | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.400 Tera per Liter | — |
| CI Stratum C | Cumulative Packed Red Blood Cell (PRBC) Volume in the Drainage Fluid During the First 24 Hours Following Surgery in Subjects Receiving ADVATE (rAHF-PFM) by Bolus (BI) or Continuous Infusion (CI) | 3.820 Tera per Liter | Standard Deviation 1.103 |
Comparison: The main analysis used a point estimate and a two-sided 95% confidence interval for ratio of the primary outcome measure of CI over BI combined over the three strata: stratum A: unilateral knee replacement, stratum B: hip surgery, stratum C: shoulder/elbow/ankle/knee (except knee replacement) surgery.p-value: 0.00195% CI: [0.816, 1.046]Hypothesis test
Secondary
Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon
The total blood loss for the postoperative period (from end of surgery until drain removal) was adjusted for the expected blood loss by applying a log-transformation of the blood loss data. The drainage volume was measured every 8 hours +/- 30 minutes during the first 24 hours. If the drainage continued beyond 24 hours, the PRBC volume and hemoglobin was to be measured cumulatively every 24 hours or whenever the drainage bottle was emptied and at the time of drain removal. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject for the first 24 hours postoperatively, and for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood
Time frame: From end of surgery (application of compressive dressing and release of tourniquet, if applicable) until drain removal (up to postoperative day 7).
Population: All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bolus Infusion | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 766.73 Milliliter | Standard Deviation 182.463 |
| Continuous Infusion | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 929.49 Milliliter | Standard Deviation 167.662 |
| BI Stratum A | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 752.91 Milliliter | Standard Deviation 42.343 |
| BI Stratum B | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 341.5 Milliliter | Standard Deviation 135.075 |
| BI Stratum C | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 1000.37 Milliliter | Standard Deviation 259.239 |
| CI Stratum A | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 899.83 Milliliter | Standard Deviation 45.459 |
| CI Stratum B | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 921.1 Milliliter | Standard Deviation 42.906 |
| CI Stratum C | Actual Postoperative Blood Loss Compared to the Expected Average Blood Loss Until Drain Removal as Predicted Preoperatively by the Surgeon | 1162.48 Milliliter | Standard Deviation 514.033 |
Secondary
Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon
Drainage fluid volume was to be measured cumulatively and recorded every 8 hours ± 30 minutes during the first 24 hours following surgery. Prior to surgery, the operating surgeon was to predict the estimated duration of surgery and the volume (mL) of the estimated expected blood loss for the surgery in a hemostatically normal individual of the same sex, age, and stature as the study subject 1) for the intraoperative procedure (defined as the time period from incision to application of compressive dressing and release of tourniquet, if applicable), 2) for the first 24 hours postoperatively, and 3) for the postoperative period until drain removal, if drainage continued beyond 24 hours. Units: Milliliter of blood
Time frame: During the first 24 postoperative hours blood loss was measured every 8 hours ± 30 minutes
Population: All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bolus Infusion | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 709.28 Milliliter | Standard Deviation 150.103 |
| Continuous Infusion | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 811.11 Milliliter | Standard Deviation 79.511 |
| BI Stratum A | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 724.48 Milliliter | Standard Deviation 66.367 |
| BI Stratum B | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 265 Milliliter | Standard Deviation 49.497 |
| BI Stratum C | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 814.03 Milliliter | Standard Deviation 171.019 |
| CI Stratum A | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 819.22 Milliliter | Standard Deviation 66.992 |
| CI Stratum B | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 713.49 Milliliter | Standard Deviation 0 |
| CI Stratum C | Actual Postoperative Blood Loss During the First 24 Hours Compared With the Average Blood Loss as Predicted Preoperatively by the Operating Surgeon | 811.25 Milliliter | Standard Deviation 163.027 |
Secondary
Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation)
Number of participants that developed Factor VIII inhibitory antibody during the study.
Time frame: Throughout the study period of approximately 9-26 weeks per participant
Population: Participants in the Safety Analysis Set treated with at least one ADVATE infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bolus Infusion | Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation) | 2 Participants |
| Continuous Infusion | Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation) | 2 Participants |
| BI Stratum A | Incidence of Factor VIII Inhibitory Antibody (≥0.4 Bethesda Units Using the Nijmegen Modification of the Bethesda Assay Formation) | 4 Participants |
Secondary
Number of Adverse Events Related to the Administration of the Study Product.
All AEs from the first study drug exposure until the study completion/discontinuation date were to be recorded. Each AE was to be evaluated by the investigator for causal relationship (i.e., unrelated, possibly related or probably related) to the study product.
Time frame: From first study drug exposure until study completion/discontinuation (approximately 9-26 weeks per subject)
Population: Participants in the Safety Analysis Set treated with at least one ADVATE infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bolus Infusion | Number of Adverse Events Related to the Administration of the Study Product. | 6 Adverse Events |
| Continuous Infusion | Number of Adverse Events Related to the Administration of the Study Product. | 8 Adverse Events |
| BI Stratum A | Number of Adverse Events Related to the Administration of the Study Product. | 14 Adverse Events |
Secondary
Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion
To simplify the results below: Bleeding episodes were reported for 4 subjects (3 subjects on bolus infusion: 2 in Stratum A and 1 in Stratum B, and 1 subject on continuous infusion/Stratum B). The 4 subjects had 1 bleeding episode each. No bleeding episodes were reported for Stratum C.
Time frame: Through Postoperative Day 7
Population: All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bolus Infusion | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.10 Bleeding Episodes | Standard Deviation 0.301 |
| Continuous Infusion | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.03 Bleeding Episodes | Standard Deviation 0.186 |
| BI Stratum A | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.08 Bleeding Episodes | Standard Deviation 0.282 |
| BI Stratum B | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.50 Bleeding Episodes | Standard Deviation 0.707 |
| BI Stratum C | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.00 Bleeding Episodes | Standard Deviation 0 |
| CI Stratum A | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.00 Bleeding Episodes | Standard Deviation 0 |
| CI Stratum B | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.50 Bleeding Episodes | Standard Deviation 0.707 |
| CI Stratum C | Number of Bleeding Episodes During Treatment With Continuous or Bolus Infusion | 0.00 Bleeding Episodes | Standard Deviation 0 |
Secondary
Number of Units of Packed Red Blood Cells Transfused
Time frame: During the first postoperative 24 hours
Population: All subjects who were randomized to receive BI or CI and have observed drainage volumes up to 24 hours including hematocrit results for these drainage fluids. The overall number of participants treated by BI and CI comprises the number of participants in Stratum A, B and C for BI and CI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bolus Infusion | Number of Units of Packed Red Blood Cells Transfused | 0.9 PRBC Units | Standard Deviation 1.2 |
| Continuous Infusion | Number of Units of Packed Red Blood Cells Transfused | 1.3 PRBC Units | Standard Deviation 1.4 |
| BI Stratum A | Number of Units of Packed Red Blood Cells Transfused | 1.0 PRBC Units | Standard Deviation 1.3 |
| BI Stratum B | Number of Units of Packed Red Blood Cells Transfused | 1.5 PRBC Units | Standard Deviation 2.1 |
| BI Stratum C | Number of Units of Packed Red Blood Cells Transfused | 0.2 PRBC Units | Standard Deviation 0.4 |
| CI Stratum A | Number of Units of Packed Red Blood Cells Transfused | 1.2 PRBC Units | Standard Deviation 1.3 |
| CI Stratum B | Number of Units of Packed Red Blood Cells Transfused | 3.5 PRBC Units | Standard Deviation 2.1 |
| CI Stratum C | Number of Units of Packed Red Blood Cells Transfused | 0.7 PRBC Units | Standard Deviation 1.2 |