Active Preoperative Anemia Management in Patients Undergoing Cardiac Surgery

NCT02189889 | Terminated Phase 1 Results DMC

• 1 other identifier: APART.V1.2013
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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. 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. 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.

Conditions

Anemia; Cardiovascular Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• # of Participants Who Adhered to the Study Protocol

  Successful adherence is defined as adhering to dosing in ≥90% of patients for ≥90% of the doses deemed appropriate by the surveillance strategy.

  Preoperative 1st dose through Postoperative Day (POD) 2.

Secondary Outcomes (4)

• 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.

• 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.

• Incidence of Pre-defined Clinical Events in Each of the Study Arms

  Preoperative 1st dose through 30 days following surgery.

Study Arms (2)

EPO and Feraheme

ACTIVE COMPARATOR

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; Drug: Feraheme

Control

NO INTERVENTION

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.

Interventions

EPO DRUG

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.

Also known as: erythropoietin

EPO and Feraheme

Feraheme DRUG

Supplementation with Feraheme, 510mg delivered as an IV infusion, will be given following the first two preoperative doses of EPO.

Also known as: IV iron

EPO and Feraheme

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• AMAG Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Clements University Hospital

Dallas, Texas, 75390-8894, United States

Location

Clements University Hospital

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007 May;83(5 Suppl):S27-86. doi: 10.1016/j.athoracsur.2007.02.099.

  PMID: 17462454 BACKGROUND

MeSH Terms

Conditions

Anemia; Cardiovascular Diseases; Anemia, Iron-Deficiency

Interventions

Erythropoietin; Ferrosoferric Oxide; ferryl iron

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Hypochromic; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Philip Greilich -PROFESSOR
• Organization: UT Southwestern Medical Center

PHILIP.GREILICH@UTSouthwestern.edu

214/645-8018

Study Officials

• Philip E. Greilich, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FASE, Professor and Holder S.T. "Buddy" Harris Distinguished Chair in Cardiac Anesthesiology, Quality Officer, University of Texas Healthcare System

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: July 15, 2014
• Study Start: April 9, 2013
• Primary Completion: July 26, 2019
• Study Completion: July 26, 2019
• Last Updated: October 23, 2020
• Results First Posted: October 23, 2020

Record last verified: 2020-10

Locations

US (2)