Anemia
Conditions
Keywords
Anemia, erythropoetin, Epoetin alfa, erythropoetin recombinant, Critical care, critical illness, intensive care
Brief summary
The purpose of this trial is to evaluate the physical function outcomes in anemic, critically ill, trauma subjects treated with epoetin alfa (PROCRIT®) compared to placebo.
Detailed description
The overall study design is based on the assumption that the maximum increase in red blood cells and their effect often does not occur while a subject is in the ICU and acutely ill. The study hypothesis is that a higher hemoglobin (red blood cells) carries more oxygen and delivers oxygen to the tissues. This should increase the ability of the injured subject to tolerate the physical exertion involved in the recuperative process and thus recover earlier than someone with a lower hemoglobin. One milliliter of a colorless liquid is injected under the subjects skin weekly during their hospital stay and weekly for up to an additional 12 weeks after hospital discharge.
Interventions
DRUGPROCRIT
40,000 IU/mL/week for max of 12 weeks
DRUGPlacebo
40,000 IU/mL/week for max of 12 weeks
Sponsors
Ortho Biotech Products, L.P.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* ICU admission secondary to a blunt multi-system traumatic injury * A leg or pelvic fracture must be one of the injuries sustained * Male or female * Age between 18 and 55 years * Hemoglobin \<=12g/dL at study entry * An expected ICU stay \>=2 days * Glascow Coma Scale (GCS) score must be \>= 13 at hospital admission or within 24 hours of admission * Documented ability to function independently prior to this hospitalization as determined by a subject or proxy interview using the Karnofsky Performance scale and having a score \>=80 * Subjects (or appropriate legal representative) must sign the informed consent form after the nature of the study has been fully explained * Female subjects that can become pregnant must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide, or surgical sterilization) during study * Subjects must be literate in their native language in order to complete written self-assessments during the post-hospital discharge phase
Exclusion criteria
* Acute burns * Traumatic Brain Injury (TBI) with admission GCS \<= 12 and/or spinal cord injury * Cause of injury secondary to a fall from a standing position * Trauma victims transferred into the participating institution \> 8 hours post injury * Subjects not expected to survive 12 months given their injuries and/or pre-existing, uncorrectable medical condition * Chronic renal failure on dialysis * Significant hematological disease * All subjects expected to undergo chemotherapy during the course of treatment * A current diagnosis of uncontrolled hypertension * New onset seizures (within three months) or seizures not controlled by medication prior to admission * Gustillo III fracture, open pelvic fracture, traumatic amputation * Prior history or diagnosis of deep vein thrombosis (DVT), pulmonary embolism (PE), or genetic coagulation abnormality * Pregnancy or lactation * Refusal to accept blood transfusion * Received an experimental drug or used an experimental medical device within 30 days prior to the planned start of treatment * Treatment with any recombinant human erythropoietin within 30 days prior to enrollment - Known hypersensitivity to human albumin or mammalian cell-derived products or epoetin alfa * Employees of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that investigator or study center
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SF-36 PF Score | Hospital Discharge to Post-Hospital Discharge Week 24 | Average SF-36 (Medical Outcome Survey Short Form) PF (Physical Function) Score post hospital discharge for each subject. Each subjects SF-36 score is the average of all the post hospital discharge scores. The SF-36 score is a patient reported questionaire related to Physical Function base the score can range from 0 to 100. The worst score is 0 and the best possible score is 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Return to Usual Activity (RTUA) | Hospital Discharge to Post-Hospital Discharge Week 24 | Number of Subjects with Week 24 SF-36 PF Score greater than or equal to their pre-trauma SF-36 PF score. The pre-trauma SF-36 PF score was collected at hosptital discharge and reflects a subjects physical function before they were injured and hospitalized. |
Countries
United States
Participant flow
Pre-assignment details
ITT subjects were all randomized subjects. Three subjects were randomized prior to screening and failed screening. These 3 subjects did not receive any study medication or procedure prior to discontinuation and are not included in the 192 subjects that started the study.
Participants by arm
| Arm | Count |
|---|---|
| PROCRIT 40,000 IU/mL/week for maximum of 12 weeks | 96 |
| Placebo Placebo given at equivalent volume (1 mL) as Procrit | 92 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 11 | 11 |
| Overall Study | Other | 4 | 5 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 5 |
| Overall Study | Sponser Request | 1 | 0 |
| Overall Study | Withdrawal by Subject | 29 | 20 |
Baseline characteristics
| Characteristic | PROCRIT | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 3 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 89 Participants | 178 Participants |
| Age, Continuous | 32.2 years STANDARD_DEVIATION 10.94 | 33.5 years STANDARD_DEVIATION 11.06 | 32.8 years STANDARD_DEVIATION 10.99 |
| Sex: Female, Male Female | 32 Participants | 35 Participants | 67 Participants |
| Sex: Female, Male Male | 64 Participants | 57 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 83 / 96 | 81 / 92 |
| serious Total, serious adverse events | 17 / 96 | 20 / 92 |
Outcome results
Primary
SF-36 PF Score
Average SF-36 (Medical Outcome Survey Short Form) PF (Physical Function) Score post hospital discharge for each subject. Each subjects SF-36 score is the average of all the post hospital discharge scores. The SF-36 score is a patient reported questionaire related to Physical Function base the score can range from 0 to 100. The worst score is 0 and the best possible score is 100.
Time frame: Hospital Discharge to Post-Hospital Discharge Week 24
Population: ITT (Intent to Treat), The number of subjects analyzed includes all ITT subjects that did not withdraw from the study prior to hospital discharge.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PROCRIT | SF-36 PF Score | 27.30 Units on a scale. | Standard Deviation 23.668 |
| Placebo | SF-36 PF Score | 30.88 Units on a scale. | Standard Deviation 23.522 |
Comparison: The null hypothesis is that there is no difference between Procrit and Placebo in average SF-36 Physical Function Scoresp-value: 0.3807ANCOVA
Secondary
Return to Usual Activity (RTUA)
Number of Subjects with Week 24 SF-36 PF Score greater than or equal to their pre-trauma SF-36 PF score. The pre-trauma SF-36 PF score was collected at hosptital discharge and reflects a subjects physical function before they were injured and hospitalized.
Time frame: Hospital Discharge to Post-Hospital Discharge Week 24
Population: Intention to Treat(ITT)population and completed Week 24 Post-Hospital discharge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PROCRIT | Return to Usual Activity (RTUA) | 9 Participants |
| Placebo | Return to Usual Activity (RTUA) | 11 Participants |
p-value: 0.7038Chi-squared