Anemia
Conditions
Keywords
anemia, function, rehabilitation
Brief summary
Patients who are admitted to subacute rehabilitation facilities following hospitalization are frequently anemic. The purpose of this study is to see if anemic patients treated with epoetin alfa will have higher hemoglobin levels and better functional recovery at 3, 8, and 12 weeks after study entry compared to patients who do not receive epoetin alfa.
Detailed description
Anemia is associated with loss of function in some studies. However, it is unknown if more rapid correction of anemia in patients who enter a rehabilitation setting after surgery or from hospitalization for acute medical problems leads to shorter rehabilitation stays and improved functional status. Patients aged 60 and older who have hemoglobin levels of less than 10.5 g/dL will be randomized to receive 8 weekly doses of either erythropoietin alfa or placebo. Functional status will be measured at baseline and then at 3, 8 and 12 weeks. The following specific aims will be tested in this study: * Determine the prevalence of anemia in patients admitted to a subacute rehabilitation facility with potential for recovery. * Determine the baseline functional status of patients admitted to a subacute rehabilitation facility with potential for recovery using the Functional Independence Measure (FIM), an assessment tool used in acute rehabilitation settings. * Determine if administration of epoetin alfa will result in higher hemoglobin concentrations in patients receiving the drug than in patients given placebo at 3, 8 and 12 weeks after entry into the study. * Perform a study that establishes the feasibility of a trial to test whether epoetin alfa produces improvements in the FIM, grip strength, the time it takes for patients to reach rehabilitation goals, activity monitor, fatigue, mood, functional recovery and reduces length of rehabilitation stay.
Interventions
Sponsors
Ortho Biotech Clinical Affairs, L.L.C.
University of Medicine and Dentistry of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 60 years of age or older * Admission hemoglobin concentration of \< 10.5 g/dL. * Able to read and understand English. * Consent signed by subjects.
Exclusion criteria
* Unable to randomize within 7 days of admission to rehabilitation center. * Folstein min-mental status score of \< 21. * Neuromuscular disease and/or disability; in clinical judgment of the investigators that do not have rehabilitation potential. * Diagnosis or evidence of carcinoma (excluding skin cancer other than melanoma) within the past five years * Admission for stroke with residual deficit * Wheelchair bound prior to acute event. * Dialysis dependent chronic renal failure * Home more than 1 hour drive from hospital. * Admitted to long term nursing or hospice care. * Active blood loss. * Known history of severe iron deficiency. * Hematological disease that results in anemia that may not respond to erythropoietin (including, but not limited to, myelodysplastic syndrome, hematological malignancy, hemolytic syndromes, hemoglobinopathy). * Uncontrolled hypertension (systolic BP \>200 mmHg or diastolic BP \>110 mmHg) after adequate antihypertensive therapy. * New onset seizures (within three months) or seizures not controlled by medication. * Objective diagnosis of pulmonary embolism or deep vein thrombosis within the past 10 years. * Patients with a condition (e.g. psychiatric illness) or in a situation that, in the investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's compliance with study procedures. * Acute burns. * Treatment with any recombinant human erythropoietin within 30 days prior to enrollment. * Known hypersensitivity to human albumin or mammalian cell-derived products or recombinant human erythropoietin (rHuEPO). * Received an experimental drug or used an experimental medical device within 30 days prior to the planned start of treatment. * Pregnancy or lactation. * 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 |
|---|---|
| Mean Hemoglobin Concentration at 8 Weeks After Entry Into the Study | 8 weeks following randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay in Subacute Rehabilitation Facility | 12 weeks following randomization | Days from randomization to discharge |
| Grip Strength | 3, 8, and 12 weeks following randomization | kilograms measured by hand held dynamometer |
| Short Physical Performance Battery (SPPB) Score | 3, 8, and 12 weeks following randomization | Measure physical function scored 0 - 12 (better) |
| Motor-FIM Score | 3, 8, and 12 weeks following randomization | FIM Motor score ranges from 13 to 91 (most independent) |
| Activity Counts | 3, 8, and 12 weeks following randomization | Activity counts as measured by the Actigraph monitor. Higher counts indicate more activity. |
| POMS Depression-Dejection Scale | 3,8,12 weeks | Profile of Mood States (POMS) Depression-Dejection Scale 15 item questionnaire to measure the degree of depressive thoughts. The scale ranges from 0 to 60 (most depressed). |
| FACIT Measurement System Fatigue Scale | 3, 8, and 12 weeks following randomization | Fatigue score ranges from 0 to 72. Lower score represents less fatigue |
Countries
United States
Participant flow
Recruitment details
Subjects recruited at two subacute rehabilitation facilities in Central New Jersey between October 2005 and March 2008
Participants by arm
| Arm | Count |
|---|---|
| Placebo & Niferex Placebo (for epoetin alpha) subcutaneous injection weekly for 8 weeks and Niferex 150 mg twice a day for 8 weeks | 11 |
| Epoetin Alpha & Niferex 40,000 IU (initial dose) epoetin alpha subcutaneous injection weekly for 8 weeks and Niferex 150 mg twice a day for 8 weeks | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo & Niferex | Epoetin Alpha & Niferex | Total |
|---|---|---|---|
| Age, Continuous | 74.4 years STANDARD_DEVIATION 8.3 | 75.5 years STANDARD_DEVIATION 8.4 | 75.0 years STANDARD_DEVIATION 8.2 |
| Days From Admit to Randomization | 5.5 Days STANDARD_DEVIATION 1.5 | 5.3 Days STANDARD_DEVIATION 1.8 | 5.4 Days STANDARD_DEVIATION 1.6 |
| FACIT Fatigue Scale | 31.6 Scores on a Scale STANDARD_DEVIATION 9.5 | 29.2 Scores on a Scale STANDARD_DEVIATION 11.6 | 30.4 Scores on a Scale STANDARD_DEVIATION 10.4 |
| FIM Motor Scale | 74.2 Scores on a Scale STANDARD_DEVIATION 8.8 | 68.8 Scores on a Scale STANDARD_DEVIATION 6.9 | 71.5 Scores on a Scale STANDARD_DEVIATION 8.2 |
| Hemoglobin Level | 9.8 g/dL STANDARD_DEVIATION 1 | 9.8 g/dL STANDARD_DEVIATION 0.6 | 9.8 g/dL STANDARD_DEVIATION 0.8 |
| POMS Depression-Dejection Scale | 3 Scores on a Scale | 3 Scores on a Scale | 3 Scores on a Scale |
| Race/Ethnicity, Customized Black | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 1 / 11 |
Outcome results
Primary
Mean Hemoglobin Concentration at 8 Weeks After Entry Into the Study
Time frame: 8 weeks following randomization
Population: Intention to treat; of the subjects not lost to follow-up, 3 subjects in the placebo arm \& 2 subjects in the epoetin alpha arm were not available for 8 week hemoglobin draw
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo & Niferex | Mean Hemoglobin Concentration at 8 Weeks After Entry Into the Study | 11.9 g/dL | Standard Deviation 1.2 |
| Epoetin Alpha & Niferex | Mean Hemoglobin Concentration at 8 Weeks After Entry Into the Study | 13.6 g/dL | Standard Deviation 0.6 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Activity Counts
Activity counts as measured by the Actigraph monitor. Higher counts indicate more activity.
Time frame: 3, 8, and 12 weeks following randomization
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo & Niferex | Activity Counts | Activity Counts at 3 weeks (n=8; n=9) | 51.13 Counts | Standard Deviation 27 |
| Placebo & Niferex | Activity Counts | Activity Counts at 8 weeks (n=9; n=6) | 58.78 Counts | Standard Deviation 32.8 |
| Placebo & Niferex | Activity Counts | Activity Counts at 12 weeks (n=10; n=8) | 61.60 Counts | Standard Deviation 27.2 |
| Epoetin Alpha & Niferex | Activity Counts | Activity Counts at 3 weeks (n=8; n=9) | 41.56 Counts | Standard Deviation 28.1 |
| Epoetin Alpha & Niferex | Activity Counts | Activity Counts at 8 weeks (n=9; n=6) | 70.17 Counts | Standard Deviation 27.3 |
| Epoetin Alpha & Niferex | Activity Counts | Activity Counts at 12 weeks (n=10; n=8) | 77.75 Counts | Standard Deviation 44.6 |
Comparison: Activity Counts at 3 weeksp-value: 0.37Wilcoxon (Mann-Whitney)
Comparison: Activity Counts at 8 weeksp-value: 0.69Wilcoxon (Mann-Whitney)
Comparison: Activity Counts at 12 weeksp-value: 0.36Wilcoxon (Mann-Whitney)
Secondary
FACIT Measurement System Fatigue Scale
Fatigue score ranges from 0 to 72. Lower score represents less fatigue
Time frame: 3, 8, and 12 weeks following randomization
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo & Niferex | FACIT Measurement System Fatigue Scale | FACIT at 3 weeks (n=8; n=9) | 38.3 Scores on a Scale | Standard Deviation 6.7 |
| Placebo & Niferex | FACIT Measurement System Fatigue Scale | FACIT at 8 weeks (n=9; n=7) | 39.8 Scores on a Scale | Standard Deviation 11.2 |
| Placebo & Niferex | FACIT Measurement System Fatigue Scale | FACIT at 12 weeks (n=10; n=8) | 42.7 Scores on a Scale | Standard Deviation 6.7 |
| Epoetin Alpha & Niferex | FACIT Measurement System Fatigue Scale | FACIT at 3 weeks (n=8; n=9) | 35.7 Scores on a Scale | Standard Deviation 10.7 |
| Epoetin Alpha & Niferex | FACIT Measurement System Fatigue Scale | FACIT at 8 weeks (n=9; n=7) | 42.3 Scores on a Scale | Standard Deviation 8.3 |
| Epoetin Alpha & Niferex | FACIT Measurement System Fatigue Scale | FACIT at 12 weeks (n=10; n=8) | 38.6 Scores on a Scale | Standard Deviation 10.4 |
Comparison: FACIT at 3 weeksp-value: 0.64Wilcoxon (Mann-Whitney)
Comparison: FACIT at 8 weeksp-value: 0.83Wilcoxon (Mann-Whitney)
Comparison: FACIT at 12 weeksp-value: 0.46Wilcoxon (Mann-Whitney)
Secondary
Grip Strength
kilograms measured by hand held dynamometer
Time frame: 3, 8, and 12 weeks following randomization
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo & Niferex | Grip Strength | Grip Strength at 3 weeks (n=9; n=10) | 19.0 kg | Standard Deviation 4 |
| Placebo & Niferex | Grip Strength | Grip Strength at 8 weeks (n=9; n=7) | 19.4 kg | Standard Deviation 3.7 |
| Placebo & Niferex | Grip Strength | Grip Strength at 12 weeks (n=10; n=8) | 17.4 kg | Standard Deviation 3.5 |
| Epoetin Alpha & Niferex | Grip Strength | Grip Strength at 3 weeks (n=9; n=10) | 18.4 kg | Standard Deviation 3.1 |
| Epoetin Alpha & Niferex | Grip Strength | Grip Strength at 8 weeks (n=9; n=7) | 19.6 kg | Standard Deviation 4.2 |
| Epoetin Alpha & Niferex | Grip Strength | Grip Strength at 12 weeks (n=10; n=8) | 19.0 kg | Standard Deviation 3.6 |
Comparison: Grip strength at 3 weeksp-value: 0.66Wilcoxon (Mann-Whitney)
Comparison: Grip strength at 8 weeksp-value: 1Wilcoxon (Mann-Whitney)
Comparison: Grip strength at 12 weeksp-value: 0.53Wilcoxon (Mann-Whitney)
Secondary
Length of Stay in Subacute Rehabilitation Facility
Days from randomization to discharge
Time frame: 12 weeks following randomization
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo & Niferex | Length of Stay in Subacute Rehabilitation Facility | 13.1 Days | Standard Deviation 5.2 |
| Epoetin Alpha & Niferex | Length of Stay in Subacute Rehabilitation Facility | 17.4 Days | Standard Deviation 9 |
p-value: 0.21Wilcoxon (Mann-Whitney)
Secondary
Motor-FIM Score
FIM Motor score ranges from 13 to 91 (most independent)
Time frame: 3, 8, and 12 weeks following randomization
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo & Niferex | Motor-FIM Score | FIM at 3 weeks (n=9; n=9) | 76.9 Scores on a Scale | Standard Deviation 4.4 |
| Placebo & Niferex | Motor-FIM Score | FIM at 8 weeks (n=9; n=7) | 81.7 Scores on a Scale | Standard Deviation 4.2 |
| Placebo & Niferex | Motor-FIM Score | FIM at 12 weeks (n=10; n=8) | 85.2 Scores on a Scale | Standard Deviation 3.8 |
| Epoetin Alpha & Niferex | Motor-FIM Score | FIM at 3 weeks (n=9; n=9) | 77.7 Scores on a Scale | Standard Deviation 5.7 |
| Epoetin Alpha & Niferex | Motor-FIM Score | FIM at 8 weeks (n=9; n=7) | 85.0 Scores on a Scale | Standard Deviation 4.4 |
| Epoetin Alpha & Niferex | Motor-FIM Score | FIM at 12 weeks (n=10; n=8) | 85.1 Scores on a Scale | Standard Deviation 5.8 |
Comparison: FIM at 3 weeksp-value: 1Wilcoxon (Mann-Whitney)
Comparison: FIM at 8 weeksp-value: 0.17Wilcoxon (Mann-Whitney)
Comparison: FIM at 12 weeksp-value: 0.59Wilcoxon (Mann-Whitney)
Secondary
POMS Depression-Dejection Scale
Profile of Mood States (POMS) Depression-Dejection Scale 15 item questionnaire to measure the degree of depressive thoughts. The scale ranges from 0 to 60 (most depressed).
Time frame: 3,8,12 weeks
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo & Niferex | POMS Depression-Dejection Scale | POMS at 3 weeks (n=9; n=10) | 1 Scores on a Scale |
| Placebo & Niferex | POMS Depression-Dejection Scale | POMS at 8 weeks (n=9; n=7) | 1 Scores on a Scale |
| Placebo & Niferex | POMS Depression-Dejection Scale | POMS at 12 weeks (n=10; n=7) | 1 Scores on a Scale |
| Epoetin Alpha & Niferex | POMS Depression-Dejection Scale | POMS at 3 weeks (n=9; n=10) | 3.5 Scores on a Scale |
| Epoetin Alpha & Niferex | POMS Depression-Dejection Scale | POMS at 8 weeks (n=9; n=7) | 0 Scores on a Scale |
| Epoetin Alpha & Niferex | POMS Depression-Dejection Scale | POMS at 12 weeks (n=10; n=7) | 0 Scores on a Scale |
Comparison: POMS at 3 weeksp-value: 0.97Wilcoxon (Mann-Whitney)
Comparison: POMS at 8 weeksp-value: 0.46Wilcoxon (Mann-Whitney)
Comparison: POMS at 12 weeksp-value: 0.68Wilcoxon (Mann-Whitney)
Secondary
Short Physical Performance Battery (SPPB) Score
Measure physical function scored 0 - 12 (better)
Time frame: 3, 8, and 12 weeks following randomization
Population: exact numbers of subjects analyzed at each time point vary based on time of study withdrawal for those who withdrew and availability of subject for those who were under active follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo & Niferex | Short Physical Performance Battery (SPPB) Score | SPPB at 3 weeks (n=9; n=9) | 3.4 Scores on a scale | Standard Deviation 1.9 |
| Placebo & Niferex | Short Physical Performance Battery (SPPB) Score | SPPB at 8 weeks (n=9; n=7) | 7.0 Scores on a scale | Standard Deviation 1.9 |
| Placebo & Niferex | Short Physical Performance Battery (SPPB) Score | SPPB at 12 weeks (n=10; n=8) | 8.0 Scores on a scale | Standard Deviation 2.3 |
| Epoetin Alpha & Niferex | Short Physical Performance Battery (SPPB) Score | SPPB at 3 weeks (n=9; n=9) | 3.7 Scores on a scale | Standard Deviation 2.5 |
| Epoetin Alpha & Niferex | Short Physical Performance Battery (SPPB) Score | SPPB at 8 weeks (n=9; n=7) | 7.4 Scores on a scale | Standard Deviation 2.9 |
| Epoetin Alpha & Niferex | Short Physical Performance Battery (SPPB) Score | SPPB at 12 weeks (n=10; n=8) | 7.1 Scores on a scale | Standard Deviation 3.1 |
Comparison: SPPB at 3 weeksp-value: 0.96Wilcoxon (Mann-Whitney)
Comparison: SPPB at 8 weeksp-value: 1Wilcoxon (Mann-Whitney)
Comparison: SPPB at 12 weeksp-value: 0.66Wilcoxon (Mann-Whitney)