Active Management of Preoperative Anemia to Reduce Erythrocyte Transfusion in Patients Undergoing Cardiac Surgery (APART)
This pilot, feasibility study is being conducted 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 trial will test the hypothesis that a short-course (1-4 weeks) of ePo plus iV iron is superior to the standard of care at reducing erythrocyte transfusions 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 study will also provide valuable information in determining whether the addition of other clinical sites with similar patient populations will be needed in order to help recruit patients for timely completion of the RCT. in addition, the study will provide important information on issues related to data collection, data management, adherence to the study protocol, transfusion and surveillance strategies and classification of clinical outcomes and adverse events.
The treatment group will receive up to three doses of ePo 300u/kg. The first dose of study medication will be administered up to 4 weeks before the day of surgery and the second will be administered 1-7 days before the day of surgery. These doses will be given at least 7 days apart. a third dose will be administered two days following surgery. all 3 doses will be administered per surveillance strategy guidelines. in addition, supplementation with iV iron (feraheme; 510mg delivered as a single injection following the first two preoperative doses of ePo) will be given. iron-deficient patients allocated to the control group (n[?]25) will receive supplementation with oral iron (325 mg, three times a day initiated during first preoperative baseline research visit).
Primary end Point:
The primary objective is to assess the enrollment rate and adherence to the dosing protocol and surveillance strategies. We define successful adherence as adherence to dosing in more than 90% of patients for more than 90% of the doses deemed appropriate by the surveillance strategy. Secondary outcomes will include changes in hemoglobin levels and reticulocyte counts within the two groups from baseline to the day of surgery (preop to PoD#0) and PoD#5, number of RBC units transfused, frequency of pre-specified clinical outcomes and incidence of adverse events in each of the study groups. Data from this pilot study will be used for the power analysis and design of the larger RCT.
Clinical outcomes will be defined using the following criteria: Society of Thoracic Surgery (STS) for stroke/transient ischemic attack (Tia), coma/encephalopathy, myocardial infarction (Mi), prolonged ventilation, reoperation for bleeding or graft occlusion/revision, postoperative venous thrombosis, thromboembolic event, deep venous thrombosis (DVT) and pulmonary embolism; RiFLe for acute renal injury (aKi), national Healthcare Safety network (nHSn) for surgical site infections (SSi); Surgenor SD et al. for low output heart failure (LoHF); any life-threatening events (i.e., subject was at substantial risk of dying at the time of the adverse event) and in-hospital or 30-day vital status based on observation. outcome data will be collected via contact with primary physician, public record review or by a follow-up telephone call by the research nurse.
The inclusion criteria of subjects are as follows:
1. The subject must be between 18 and 80 years old.
2. The subject must be diagnosed with preoperative anemia, defined as hemoglobin <13.0g/dL.
3. The subject must be scheduled for elective cardiac surgery (CABG, valve, or CABG/valve).
4. Female subjects of child bearing potential must have a documented negative pregnancy test
within 7 days prior to the procedure.
5. The subject must sign a written informed consent prior to the procedure, using a form that is
approved by the UT Southwestern Institutional Review Board.
6. The subject must agree to be compliant and return for all follow-up visits.