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Active Preoperative Anemia Management in Patients Undergoing Cardiac Surgery (APART)

This study is currently recruiting participants.
Verified February 2017 by Philip Greilich, University of Texas Southwestern Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02189889
First Posted: July 15, 2014
Last Update Posted: February 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
AMAG Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Philip Greilich, University of Texas Southwestern Medical Center
  Purpose

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.

  1. 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.
  2. 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.


Condition Intervention Phase
Anemia Cardiovascular Disease Drug: EPO Drug: Feraheme Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Active Preoperative Anemia Management to Reduce Erythrocyte Transfusion in Patients Undergoing Cardiac Surgery (APART): A Pilot, Feasibility Study

Resource links provided by NLM:


Further study details as provided by Philip Greilich, University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Assessment of adherence rate to the dosing protocol per surveillance strategy. [ Time Frame: 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.


Secondary Outcome Measures:
  • Change from Baseline hemoglobin level assessed at different time points within the 2 arms. [ Time Frame: Change from Baseline hemoglobin level to day of surgery (DOS), to POD 5. ]
  • Change from Baseline reticulocyte count assessed at different time points within the 2 arms. [ Time Frame: Change from Baseline reticulocyte count to DOS, to POD 5. ]
  • Number of blood products utilized per patient receiving erythrocyte transfusions. [ Time Frame: Preoperative 1st dose through 30 days following surgery. ]
    Number of blood products utilized per patient receiving erythrocyte transfusions, including red blood cells, platelets and plasma.

  • Incidence of pre-defined clinical events in each of the study arms. [ Time Frame: Preoperative 1st dose through 30 days following surgery. ]
    Incidence of mortality, major cardiac, renal, neurological events (associated with anemia) and infection. These events will include myocardial infarction, prolonged low-output state, encephalopathy, duration of mechanical ventilation, renal insufficiency,mortality and dialysis dependence at 30 days.


Other Outcome Measures:
  • Analysis of resource utilization. [ Time Frame: Preoperative 1st dose through discharge, or POD 30 (whichever comes first). ]
    The cost of red cell transfusions, EPO plus iron, direct hospital costs and direct margins associated with the care of those randomized in this pilot study will be recorded for future analysis of resource utilization. The duration of operating room time, intensive care unit and hospital length of stay will be collected. The total cost of erythrocyte transfusion will be based on four times the acquisition cost ($1,200.00).


Estimated Enrollment: 50
Study Start Date: April 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: EPO
The treatment group will receive up to three doses of EPO 300U/kg. The first dose of study medication will be administered up to 28 days before the day of surgery and the second will be administered 1-7 days before the day of surgery. These first two doses will be given at least 7 days apart. A third dose may be administered two days following surgery. All 3 doses will be administered per surveillance strategy guidelines.
Other Name: erythropoietin
Drug: Feraheme
Supplementation with Feraheme, 510mg delivered as an IV infusion, will be given following the first two preoperative doses of EPO.
Other Name: IV iron
No Intervention: Control
The control group will receive no preoperative intervention for anemia. The exception being iron deficiency anemia found during baseline. If laboratory values indicate iron deficiency, oral iron will be recommended to take until surgery.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02189889


Contacts
Contact: Kenni Landgraf, RN, BSN 214-645-8087 kenni.landgraf@utsouthwestern.edu
Contact: Philip Greilich, MD 214-645-8018 philip.greilich@utsouthwestern.edu

Locations
United States, Texas
Clements University Hospital Recruiting
Dallas, Texas, United States, 75390-8894
Contact: Kenni Landgraf, RN, BSN    214-645-8087    kenni.landgraf@utsouthwestern.edu   
Contact: Tonis Roberts    214-645-8018    tonis.roberts@utsouthwestern.edu   
Principal Investigator: Philip E. Greilich, MD         
Sub-Investigator: Michael Wait, MD         
Sub-Investigator: Sarah Wright, DPharm         
Sub-Investigator: Eric Rosero, MD         
Sub-Investigator: Pietro Bajona, MD         
Sub-Investigator: Burner James, MD         
Clements University Hospital Recruiting
Dallas, Texas, United States, 75390
Contact: Kenni Landgraf, RN, BSN    214-645-8087    kenni.landgraf@utsouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
AMAG Pharmaceuticals, Inc.
Investigators
Principal Investigator: Philip E. Greilich, MD University of Texas Southwestern Medical Center
  More Information

Publications:
Responsible Party: 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
ClinicalTrials.gov Identifier: NCT02189889     History of Changes
Other Study ID Numbers: APART.V1.2013
First Submitted: July 11, 2014
First Posted: July 15, 2014
Last Update Posted: February 9, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: All data and information collected during this study will be considered confidential and remains the sole property of UTSW Medical Center. Data may be shared with AMAG Pharmaceuticals, Inc., prior to any publications. All data used in the analysis and summary of this study will be anonymous, and without reference to specific subject names.

Keywords provided by Philip Greilich, University of Texas Southwestern Medical Center:
Active preoperative anemia management
Erythrocyte transfusion
RBC transfusion
Red cell transfusion
Transfusion in cardiac surgery
Anemia treatment with erythropoietin
Anemic cardiac surgery patients
Erythrocyte stimulating agent (ESA)
Iron deficiency anemia
EPO
Feraheme

Additional relevant MeSH terms:
Anemia
Cardiovascular Diseases
Hematologic Diseases
Epoetin Alfa
Ferrosoferric Oxide
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions