Active Preoperative Anemia Management to Reduce Erythrocyte Transfusion in Patients Undergoing Cardiac Surgery (APART): A Pilot, Feasibility Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- # of Participants Who Adhered to the Study Protocol
研究概览
简要总结
Anemia which is a decreased blood count or lower than normal hemoglobin (hgb), is a major health problem for patients having heart surgery. Hemoglobin is the part of our blood that carries oxygen from the lungs to the rest of the body. Anemia that is present before surgery, called preoperative anemia, is a risk factor for an increased chance of morbidity (illness) and/or mortality (death) after heart surgery. It is also an important indicator of blood transfusion necessity. Recent clinical research investigations done to study preoperative anemia suggest a blood transfusion can damage the immune system (the system that protects us from disease) which can lead to infection, organ dysfunction (especially of the heart, kidney, brain), prolonged hospital stays, as well as increased supplies, resources and cost in surgical patients. Comprehensive anemia management can reduce or eliminate the need for blood transfusions and provide better outcomes after surgery. Therefore, controlling anemia before surgery is extremely important, and could be a lifesaving measure.
This pilot, feasibility study is being done for several reasons. First of all, it will test the the safety and effectiveness of using a short-course of two medications, erythropoietin (EPO) and Feraheme (iron given intravenously [IV]), to increase hemoglobin levels in order to improve preoperative anemia, reduce transfusions and lower postoperative complications in anemic patients undergoing heart surgery. Secondly, findings will be used to design a large randomized controlled trial (RCT). The RCT will establish a protocol to actively manage anemia before surgery, thus reducing transfusions during surgery and improving recovery afterwards. It will also help identify valuable information regarding what needs to be done for timely completion of the planned RCT.
EPO is a medication approved by the Food and Drug Administration (FDA) used to treat anemia in patients with certain conditions in order to reduce blood transfusions. And although approved for use during surgery, it has not been FDA approved for use in cardiac (heart) or vascular (blood vessels, including veins and arteries) surgery. Common side effects include nausea, vomiting, itching, headache, injection site pain, chills, deep vein thrombosis (blood clot), cough, and changes in blood pressure (BP). Feraheme is an iron replacement product approved for the treatment of low iron anemia in adult patients. It may cause serious allergic reactions, including anaphylaxis (severe, whole body allergic reaction), as well as low BP and excessive iron storage.
Patients meeting all eligibility requirements that consent to participate will be randomized into the study. Randomization is being placed by chance (like a flip of a coin) into one of two study groups, the treatment group or the control group. There is an equal chance of being placed into either group, which will be done by a computer.
- The Treatment Group will receive a 300 unit (U) per kilogram (kg) injection of EPO and a 510 milligram (mg) IV infusion of Feraheme 7-28 days before the day of surgery. And again 1-7 days before the day of surgery, a second dose of both of these medications will be given. The third dose, of EPO only, will be administered 2 days after surgery. Before initiating a dose or giving a subsequent dose, laboratory parameters will be measured to assess the hemoglobin level and response to the medication. If blood values increase too rapidly or are too high, the meds will not be started or, if already dosed, they will not be given again.
- The Control Group will receive no preoperative intervention for anemia unless lab results show iron deficiency anemia. The control group will be screened for the presence of iron deficiency anemia by evaluating blood laboratory values drawn during the baseline or preoperative visit. If lab results indicate iron deficiency anemia, over-the-counter oral iron will be recommended, to take until the day of surgery. In doing so, patients may benefit by potentially reducing the need for blood transfusions.
Data will be collected from all participants from the preoperative visits throughout the admission, including lab results, medications, vital signs, information about the procedure, transfusions, and any problems or adverse events.
详细描述
Anemia and transfusion are independent predictors of morbidity and mortality in the cardiac surgical patient population. Even so, active preoperative anemia management is not currently the standard of care at our institution. Cost associated with erythrocyte transfusions at University of Texas Southwestern (UTSW) University Hospitals exceeds twenty million dollars annually, not including costs associated with treatment of known complications of red cell transfusions (renal insufficiency, respiratory failure, infection and prolonged length of stay, etc). Fifty percent of our cardiac surgical population suffer from preoperative anemia and 79% of these patients will receive one or more red blood cell (RBC) transfusions. In contrast, the incidence of RBC transfusion was only 35% in those without preoperative anemia in the calendar year 2011-12.
The mechanism of injury in patients with preoperative anemia is either the duration/intensity of the anemia exposure and resultant organ ischemia, or the harmful effects of erythrocyte transfusion(s) itself. Active preoperative anemia management is a strategy that attempts to minimize both of these events, and in doing so, exert an additive or possibly synergistic effect on improving clinical outcomes. A randomized controlled trial utilizing a standardized transfusion strategy is a necessary step in determining if increases in preoperative hemoglobin lead to improved outcomes. A pilot, feasibility study is the first essential step in insuring the adequacy of future trials designed to answer this important question.
The APART study is being conducted to test the safety and efficacy of using a short-course (1-4 weeks) of EPO plus Feraheme to increase erythrocyte mass. The findings will be used to guide the design of a randomized, controlled trial (RCT) that examines the effects of active preoperative anemia management on erythrocyte transfusion and clinical outcomes. The RCT will test the hypothesis that a short-course (1-4 weeks) of EPO plus Feraheme is superior to the standard of care (SOC) at reducing transfusion and improving outcomes in anemic patients scheduled for cardiac surgery. Means and standard deviations derived from pilot data on changes in hemoglobin levels, reticulocyte counts and differences in erythrocyte transfusions and clinical outcomes will be analyzed for possible use in sample size calculations for the larger RCT. This pilot will also provide information in determining logistics for timely completion of the RCT, and will also address data collection, data management, adherence to the study protocol, transfusion and surveillance strategies and classification of clinical outcomes and adverse events.
Pilot Study Specific Aims Include:
- To determine the proportion of patients who fulfill all the eligibility criteria for the study and agree to be part of a randomized trial of short-course EPO plus supplemental Feraheme (up to 3 doses given over a 1-4 week interval prior to surgery) vs. standard of care management in patients scheduled for coronary bypass grafting (CABG), valve surgery, or CABG/valve surgery.
- To determine the adherence of patients and health care team to the procedures included in the study protocol (scheduled appointments, surveillance and transfusion strategies).
- To determine the increase in hemoglobin levels and reticulocyte counts following a short-course of EPO plus supplemental Feraheme over a 1-4 week interval prior to the date of surgery vs. standard of care management in patients scheduled for CABG, valve, or CABG/valve surgery.
- To assess differences in the proportion of patients receiving erythrocyte transfusions and number of blood products utilized (RBC, platelets and plasma) in the peri- and post-operative periods for those receiving a short-course of EPO plus supplemental Feraheme vs. standard of care management in patients scheduled for CABG, valve or CABG/valve surgery.
- To determine the frequency and intensity of pre-defined clinical outcomes (mortality, major cardiac, renal, neurological events [associated with anemia] and infection) in the peri- and post-operative periods for those receiving a short-course of EPO plus Feraheme vs. standard of care management in patients scheduled for CABG, valve, or CABG/valve surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •between the age of 18 and 80 years old
- •diagnosed with preoperative anemia, defined as hemoglobin <13.0 grams per deciliter (g/dL)
- •scheduled for elective cardiac surgery (CABG, valve, or CABG/valve), including both first time and repeat procedures
- •documented negative pregnancy test within 7 days prior to the procedure for females of child-bearing potential
- •a written informed consent prior to any procedure, using a form that is approved by the UT Southwestern Institutional Review Board
- •agreement to be compliant
排除标准
- •uncontrolled hypertension (defined as systolic pressure greater than 180 millimeters of mercury (mmHg), diastolic pressure greater than 100mmHg, not adequately controlled by anti-hypertensive therapy at the time of procedure)
- •current renal failure on dialysis or serum creatinine >3.0 milligrams per deciliter (mg/dL)
- •unstable angina (defined by chest pain and EKG changes indicating ischemia at rest)
- •thromboembolism within the past year
- •current active primary or metastatic malignancy or history of myeloid malignancy
- •seizures within the past year
- •history of stroke within the last 6 months
- •patients who have platelet count lower than 50,000 per cubic millimeter (mm3) or coagulation abnormality
- •sepsis or bacteremia defined by positive blood culture
- •patients who have known hypersensitivity to EPO or any of its components
- •patients who have known hypersensitivity to Feraheme or any of its components
- •patients who refuse blood transfusion, (i.e. Jehovah's Witnesses)
- •pregnant or breast feeding
- •patients who are unable to provide informed consent or who has inability to understand or corporate with study procedure
研究组 & 干预措施
EPO and Feraheme
Patients in the treatment group will receive a subcutaneous injection of EPO 300U/kg at the Baseline visit, the Preoperative visit and on POD 2; and an infusion of Feraheme 510mg at the Baseline visit and the Preoperative visit.
干预措施: EPO (Drug)
EPO and Feraheme
Patients in the treatment group will receive a subcutaneous injection of EPO 300U/kg at the Baseline visit, the Preoperative visit and on POD 2; and an infusion of Feraheme 510mg at the Baseline visit and the Preoperative visit.
干预措施: Feraheme (Drug)
结局指标
主要结局
# of Participants Who Adhered to the Study Protocol
时间窗: Preoperative 1st dose through Postoperative Day (POD) 2.
Successful adherence is defined as adhering to dosing in ≥90% of patients for ≥90% of the doses deemed appropriate by the surveillance strategy.
次要结局
- Change From Baseline Hemoglobin Level Assessed at Different Time Points Within the 2 Arms.(Change from Baseline hemoglobin level to day of surgery (DOS), to POD 5.)
- Incidence of Pre-defined Clinical Events in Each of the Study Arms(Preoperative 1st dose through 30 days following surgery.)
- Change From Baseline Reticulocyte Count Assessed at Different Time Points Within the 2 Arms.(Change from Baseline reticulocyte count to DOS, to POD 5.)
- Number of Blood Products Utilized Per Patient Receiving Erythrocyte Transfusions.(Preoperative 1st dose through 30 days following surgery.)
研究者
Philip Greilich
MD, FASE, Professor and Holder S.T. "Buddy" Harris Distinguished Chair in Cardiac Anesthesiology, Quality Officer, University of Texas Healthcare System
University of Texas Southwestern Medical Center