Anemia, Iron-Deficiency
Conditions
Keywords
anemia
Brief summary
The goal of this study is to gain further insight into the comparative effectiveness of treating patients, who are found to be anemic before their elective surgery, with a series of weekly subcutaneous doses of a drug given before surgery, which stimulates the natural production of red blood cells (a so-called erythropoietic stimulating agent \[ESA\]) along with intravenous iron, in reducing the need for blood transfusions (donated by someone other than the patient) during and after adult total hip arthroplasty (hip replacement surgery). The effects of a Preoperative Anemia Management Program (PAMP) on the patient's quality of recovery, health-related quality of life, fatigue, and rehabilitation pattern after surgery will also be examined. A cost-effectiveness analysis will be performed to compare the cost of these commercially available, FDA-approved medications versus the cost of transfused blood
Detailed description
Patient blood management (PBM) involves the timely and conscientious use of the current best evidence in making medical and surgical decisions about the care of patients to maintain red blood cell levels, optimize blood clotting, and minimize blood loss, in an effort to improve patient outcome. PBM focuses on the treatment of the individual patient and comprises transfusion therapy and drug therapy. PBM is based on three points: (1) optimization of the (preoperative) red blood cell volume, (2) reduction of diagnostic, therapeutic, or intraoperative blood loss, and (3) increasing individual tolerance towards anemia and accurate blood transfusion triggers. PBM primarily identifies patients at risk for transfusion and provides a management plan aimed at reducing or eliminating anemia and the need for blood transfusion donated from someone other than the patient (allogeneic transfusion), thus reducing the risks, blood bank inventory pressures, and the escalating costs associated with transfusion. The implementation of a formal UAB Preoperative Anemia Management Program (PAMP) may help achieve consistent PBM. Efforts will be made to coordinate patients' scheduled surgery date and their initial evaluation in the UAB Highlands Hospital Preoperative Assessment, Consultation, and Treatment (HPACT) Clinic, so that their first PACT Clinic visit occurs approximately 14 days prior to the planned total hip replacement or total knee replacement
Interventions
DRUGIron sucrose
AMG patients will receive a standardized and well-accepted intravenous dose of 200 mg of iron sucrose (Venofer®) at -14 days and -7 days before their planned surgery, and if indicated, based upon laboratory testing on the day of their surgery (if patient has a Hgb \< 13.0 g/dL and hematocrit between 30% and 39%, for males and females). An additional dose will be given on postoperative day 2.
DRUGEpoetin Alfa
AMG patients will receive a standardized and well-accepted subcutaneous dose of 40,000 IU of epoetin alfa (PROCRIT®) plus an intravenous dose of 200 mg of iron sucrose (Venofer®) at -14 days and -7 days before their planned surgery, and if indicated, based upon laboratory testing on the day of their surgery (if patient has a Hgb \< 13.0 g/dL and hematocrit between 30% and 39%, for males and females).
OTHERBlood Transfusion
An evidence-based, goal-directed blood transfusion protocol will be applied in AMG, CTG, and NAG patients during and after their surgical procedure to control for health provider variation in transfusion criteria and practices. This blood conservation protocol will consist primarily of the application of a restrictive transfusion trigger (Hgb \< 8 g/dl) (21,22) but will also take into consideration the patient's intraoperative estimated allowable blood loss and hemodynamic stability.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. 19 years to 80 years of age 2. American Society of Anesthesiologists 1-3 status 3. Undergoing total hip arthroplasty for osteoarthritis, (either a primary or replacement procedure, but not a revision procedure) OR avascular necrosis (AVN); OR undergoing total knee arthroplasty (replacement) for osteoarthritis
Exclusion criteria
1. American Society of Anesthesiologists 4 status 2. Severe anemia, defined as a hematocrit of \< 30% 3. History of hypercoagulability or thrombophilia (e.g, factor V Leiden) 4. History of deep venous thrombosis (DVT) or venous thromboembolism (VTE) within last 12 months 5. Current use of anticoagulants (e.g., heparin, warfarin, dabigatran, etc) 6. Diagnosis of chronic renal insufficiency requiring dialysis 7. Morbid obesity (BMI \> 40) 8. History of allergic reaction to intravenous iron 9. History of allergic reaction to an erythropoietic stimulating agent (ESA) 10. History of sickle cell disease 11. History of hemochromatosis 12. History of liver dysfunction or congestive heart failure 13. History of substance abuse disorder 14. History of major psychiatric disorder (e.g., major depression, bipolar disorder, axis II personality disorder, schizophrenia) 15. Uncontrolled hypertension (defined as a systolic pressure ≥ 160 mmHg and/or a diastolic pressure ≥ 110 mmHg) 16. History of uncontrolled cardiac arrhythmias, cerebrovascular accident (CVA), transient ischemic attack (TIA), acute coronary syndrome (ACS), or other arterial thrombosis. ACS includes unstable angina, Q wave myocardial infarction (QwMI), and non-Q wave myocardial infarction (NQMI) within 6 months 17. History of pure red cell aplasia (PRCA) after treatment with an ESA 18. History of seizure disorder 19. Any active/current cancer within the last 12 months (not including non-melanoma skin cancer) 20. Pregnancy or lactation 21. Non-native English speaker (because validated Spanish language versions of two of the patient questionnaires are not available)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Requiring at Least One Blood Transfusion During Surgery. | During surgery (less than 1 day) | The number of subjects who had blood transfusions (at least 1) during surgery |
| Number of Subjects With Blood Transfusions After Surgery and Prior to Discharge From Hospital | post surgery through discharge, an average of 2 days | Number of subjects that had at least 1 blood transfusion from the end of surgery until discharge from hospital |
| Number of Subjects Requiring Blood Transfusions Post Hospital Discharge Through 90 Days After Surgery | post hospital discharge through 90 days after surgery | number of subjects requiring blood transfusions after hospital discharge through 90 days after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health-related Quality of Life | Baseline at 14 days before, on hospital discharge, and at two-weeks, 30 days, 60 days and 90 days after surgery | Health-related quality of life measured with the SF-12V2; Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Questionnaire; Oxford Hip Score or Oxford Knee Score; and Multidimensional Assessment of Fatigue (MAF) Scale |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anemia Treatment Group (AMG) Group of patients who are diagnosed preoperatively as being anemic (defined as a Hgb \< 13.0 g/dL and MCV \< 100 fL, with a hematocrit between 30% and 39%, for males and females), who will receive an ESA (PROCRIT) and iron (Venofer) preoperatively.
Iron sucrose: AMG patients will receive a standardized and well-accepted intravenous dose of 200 mg of iron sucrose (Venofer®) at -14 days and -7 days before their planned surgery, and if indicated, based upon laboratory testing on the day of their surgery (if patient has a Hgb \< 13.0 g/dL and hematocrit between 30% and 39%, for males and females). An additional dose will be given on postoperative day 2.
Epoetin Alfa: AMG patients will receive a standardized and well-accepted subcutaneous dose of 40,000 IU of epoetin alfa (PROCRIT®) plus an intravenous dose of 200 mg of iron sucrose (Venofer®) at -14 days and -7 days before their planned surgery, and if indicated, based upon laboratory testing on the day of their surgery (if patient has | 5 |
| Conventional Treatment Group (CTG) Group of patients who are diagnosed preoperatively as being anemic (defined as a Hgb \< 13.0 g/dL and MCV \< 100 fL, with a hematocrit between 30% and 39%, for males and females), who will receive our current, conventional perioperative standard of care, which does not involve any preoperative anemia management (other than laboratory testing). CTG patients will undergo routine perioperative laboratory testing/screening.
Blood Transfusion: An evidence-based, goal-directed blood transfusion protocol will be applied in AMG, CTG, and NAG patients during and after their surgical procedure to control for health provider variation in transfusion criteria and practices. This blood conservation protocol will consist primarily of the application of a restrictive transfusion trigger (Hgb \< 8 g/dl) (21,22) but will also take into consideration the patient's intraoperative estimated allowable blood loss and hemodynamic stability. | 6 |
| Non Anemia Group (NAG) Group of patients who are not anemic preoperatively, who will receive our current, conventional perioperative standard of care.
Blood Transfusion: An evidence-based, goal-directed blood transfusion protocol will be applied in AMG, CTG, and NAG patients during and after their surgical procedure to control for health provider variation in transfusion criteria and practices. This blood conservation protocol will consist primarily of the application of a restrictive transfusion trigger (Hgb \< 8 g/dl) (21,22) but will also take into consideration the patient's intraoperative estimated allowable blood loss and hemodynamic stability. | 40 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Study Terminated | 5 | 6 | 40 |
Baseline characteristics
| Characteristic | Anemia Treatment Group (AMG) | Conventional Treatment Group (CTG) | Non Anemia Group (NAG) | Total |
|---|---|---|---|---|
| Age, Continuous | 63 Years | 62 Years | 62 Years | 62 Years |
| Region of Enrollment United States | 5 participants | 6 participants | 40 participants | 51 participants |
| Sex/Gender, Customized Females | 1 participants | 6 participants | 15 participants | 22 participants |
| Sex/Gender, Customized Males | 4 participants | 0 participants | 25 participants | 29 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 | 0 / 5 | 0 / 6 | 0 / 40 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 0 / 40 |
Outcome results
Primary
Number of Subjects Requiring at Least One Blood Transfusion During Surgery.
The number of subjects who had blood transfusions (at least 1) during surgery
Time frame: During surgery (less than 1 day)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anemia Treatment Group (AMG) | Number of Subjects Requiring at Least One Blood Transfusion During Surgery. | 0 Participants |
| Conventional Treatment Group (CTG) | Number of Subjects Requiring at Least One Blood Transfusion During Surgery. | 0 Participants |
| Non Anemia Group (NAG) | Number of Subjects Requiring at Least One Blood Transfusion During Surgery. | 0 Participants |
Primary
Number of Subjects Requiring Blood Transfusions Post Hospital Discharge Through 90 Days After Surgery
number of subjects requiring blood transfusions after hospital discharge through 90 days after surgery
Time frame: post hospital discharge through 90 days after surgery
Population: Subjects dropped out of study prior to day 90
Primary
Number of Subjects With Blood Transfusions After Surgery and Prior to Discharge From Hospital
Number of subjects that had at least 1 blood transfusion from the end of surgery until discharge from hospital
Time frame: post surgery through discharge, an average of 2 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anemia Treatment Group (AMG) | Number of Subjects With Blood Transfusions After Surgery and Prior to Discharge From Hospital | 0 participants |
| Conventional Treatment Group (CTG) | Number of Subjects With Blood Transfusions After Surgery and Prior to Discharge From Hospital | 1 participants |
| Non Anemia Group (NAG) | Number of Subjects With Blood Transfusions After Surgery and Prior to Discharge From Hospital | 0 participants |
Secondary
Health-related Quality of Life
Health-related quality of life measured with the SF-12V2; Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Questionnaire; Oxford Hip Score or Oxford Knee Score; and Multidimensional Assessment of Fatigue (MAF) Scale
Time frame: Baseline at 14 days before, on hospital discharge, and at two-weeks, 30 days, 60 days and 90 days after surgery
Population: No subject data was analyzed.