Anemia
Conditions
Brief summary
The purpose of this study is to determine if there is a difference in outcomes between liberal transfusion (transfusing when hemoglobin drops below a set higher value number) and conservative transfusion (transfusing when hemoglobin drops below a set lower value number).
Detailed description
Transfusion of Orthopaedic trauma patients is routinely done in asymptomatic individuals as there is no accepted national standard or recommendations from the American Academy of Orthopaedic Surgeons or the Orthopaedic Trauma Association for what level of anemia is appropriate in an asymptomatic patient. Individual practitioners typically make this decision based on anecdotal experiences and expert opinion. No prospective study has been performed to date to answer this question in this patient population. The null hypothesis of this proposed pilot study is that no difference will be seen with a liberal transfusion strategy to keep a patient's hemoglobin above 7 g/dL versus a conservative strategy to keep the patient's hemoglobin above 5.5 g/dL in patients asymptomatic at rest. The primary outcome of this pilot study will be infection; defined as postoperative wound infection (superficial or deep) or other perioperative infection but not surgical site (urinary tract infection or pneumonia). Deep infection is defined as the need for intravenous antibiotics or a return to surgery for debridement. Superficial infection is defined as the use of oral antibiotics only successfully treat a surgical site infection. Secondary outcomes will include pulmonary embolism, deep venous thrombosis, acute renal failure or insufficiency, nonunion, delayed union, compartment syndrome, osteomyelitis, nerve palsy, anoxic brain injury, cardiac ischemia or infarct, pancreatitis, or death, and the musculoskeletal functional assessment.
Interventions
BIOLOGICALBlood and blood products for transfusion
Randomization would not occur until the patient's Hgb dropped below 7 g/dL. If the patient is randomized to the liberal arm, they would be transfused to keep their Hgb \>7 g/dL. If the patient is randomized to the conservative arm, they would not be transfused until their Hgb drops below 5.5 g/dL. If the patient's Hgb does not drop below 7.0 g/dL, randomization will not be done.
Sponsors
Atlanta Medical Center
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Trauma patients admitted to participating hospital with any Orthopaedic injury who have been determined to be stable by the Trauma Service (General Surgery) and are no longer within the resuscitation phase of initial treatment. This is defined as a normal urine output (greater than 0.5 ml/kg/hr) and a systolic blood pressure greater than 90 mmHg for greater than 6 hours without fluid bolus or transfusion during that time * Age 18-50 * Hemoglobin less than 9 g/dL or expected drop below 9 g/dL with planned surgery
Exclusion criteria
* Pregnant ( urine pregnancy test will be done as standard of care) * Prisoner * Head injury (Glasgow Coma Scale less than 8 over 48 hours from presentation) * Known cardiac (coronary artery disease, atrial fibrillation, stent placement, congestive heart failure), renal (acute or chronic renal insufficiency or failure, defined as having Serum Creatinine \>1.2 at time of enrollment), liver (Childs C cirrhosis) or pulmonary disease (chronic obstructive pulmonary disease, abnormal pulmonary function tests or history of poor pulmonary function from any cause including acute traumatic conditions such as ARDS) * Unlikely to follow up in the surgeon's estimation * Sickle Cell Anemia * History of cancer * Preexisting weakness, paresthesias, deformities, or other conditions which might affect functional outcome in the surgeon's opinion * Spinal cord injury * Patients with burns expected to require operative treatment * COVID positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Wound Infection (Superficial or Deep) or Other Perioperative Infection | one year | Deep infection is defined as the need for intravenous antibiotics and/or a return to surgery for debridement. Superficial infection is defined as clinical diagnosis of cellulitis or other superficial infection treated with oral antibiotics only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined Secondary Outcomes | one year | Combined (any) Secondary Outcomes: pulmonary embolism, deep venous thrombosis, acute renal failure or insufficiency, nonunion, delayed union, compartment syndrome, osteomyelitis, nerve palsy, anoxic brain injury, cardiac ischemia or infarct, pancreatitis, or death. |
| Musculoskeletal Function Assessment | one year | The Musculoskeletal Function Assessment (MFA) evaluates the health status of patients with musculoskeletal disorders of the extremities, including patients with fractures and soft tissue injuries, repetitive motion disorders, osteoarthritis or rheumatoid arthritis. It describes patient functioning, assesses outcomes of surgical interventions and clinical trials, and monitors patients' functional status over time. The MFA is scored from 0 to 100 with 0 representing no dysfunction. Higher MFA scores/values represent a higher levels of dysfunction or worse outcome. |
Participant flow
Recruitment details
Participants were recruited based on physician referral at 3 level 1 trauma centers between March 2014 and May 2021. The first patient was enrolled on March 11, 2014 and the last participant was enrolled on May 7, 2021.
Pre-assignment details
Screening/IC done on 161 patients with a Hgb of ≤9g/dL or whose Hgb was expected to drop below 9g/dL with planned procedures/continued (controlled) bleeding. Randomization assignment occurred once patient's Hgb dropped below 7g/dL. Out of the 161 patient that consented, there were 61 whose Hgb did not drop below 7g/dL and randomization was not performed on. Those 61 patients were considered screen failures, leaving 100 patients who were randomized to either liberal or conservative transfusion.
Participants by arm
| Arm | Count |
|---|---|
| Liberal Transfusion Transfusion will be done to keep Hgb \>7 g/dL. | 49 |
| Conservative Transfusion Transfusion will be done to keep Hgb \> 5.5 g/dL. | 50 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 19 | 15 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Liberal Transfusion | Conservative Transfusion | 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 | 49 Participants | 50 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 4 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 41 Participants | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 18 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 27 Participants | 29 Participants | 56 Participants |
| Region of Enrollment United States | 49 participants | 50 participants | 99 participants |
| Sex: Female, Male Female | 16 Participants | 19 Participants | 35 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 50 |
| other Total, other adverse events | 0 / 49 | 0 / 50 |
| serious Total, serious adverse events | 7 / 49 | 6 / 50 |
Outcome results
Primary
Postoperative Wound Infection (Superficial or Deep) or Other Perioperative Infection
Deep infection is defined as the need for intravenous antibiotics and/or a return to surgery for debridement. Superficial infection is defined as clinical diagnosis of cellulitis or other superficial infection treated with oral antibiotics only.
Time frame: one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liberal | Postoperative Wound Infection (Superficial or Deep) or Other Perioperative Infection | 12 Participants |
| Conservative | Postoperative Wound Infection (Superficial or Deep) or Other Perioperative Infection | 3 Participants |
p-value: 0.0122Fisher Exact
Secondary
Combined Secondary Outcomes
Combined (any) Secondary Outcomes: pulmonary embolism, deep venous thrombosis, acute renal failure or insufficiency, nonunion, delayed union, compartment syndrome, osteomyelitis, nerve palsy, anoxic brain injury, cardiac ischemia or infarct, pancreatitis, or death.
Time frame: one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liberal | Combined Secondary Outcomes | 7 Participants |
| Conservative | Combined Secondary Outcomes | 6 Participants |
p-value: 0.7742Fisher Exact
Secondary
Musculoskeletal Function Assessment
The Musculoskeletal Function Assessment (MFA) evaluates the health status of patients with musculoskeletal disorders of the extremities, including patients with fractures and soft tissue injuries, repetitive motion disorders, osteoarthritis or rheumatoid arthritis. It describes patient functioning, assesses outcomes of surgical interventions and clinical trials, and monitors patients' functional status over time. The MFA is scored from 0 to 100 with 0 representing no dysfunction. Higher MFA scores/values represent a higher levels of dysfunction or worse outcome.
Time frame: one year
Population: Sixty five patients completed 1 year follow up but 5 declined to complete the MFA, leaving sixty patients that completed 1 year MFA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liberal | Musculoskeletal Function Assessment | 35.9 score on a scale | Standard Deviation 21.1 |
| Conservative | Musculoskeletal Function Assessment | 28.2 score on a scale | Standard Deviation 19.4 |
p-value: 0.1443t-test, 1 sided