Effect of Intravenous Ferric Carboxymaltose on Hemoglobin Response and Transfusion in Patients With Iron Deficiency Anemia After Off-Pump Coronary Artery Bypass Grafting

In this prospective open-label randomized tral, 100 patients with elective off-pump coronary artery bypass (OPCAB) or minimal invasive direct coronary bypass (MIDCAB) surgery were enrolled. Before surgery, if a patient had iron deficiency anemia, the patient was randomized to receive Ferinject®(Ferric carboxymaltose, n=50) or placebo (normal saline, n=50), respectively. A single dose should not exceed 1000mg of iron per day or 20mg per kg body weight. In addition, the administration of 1000mg of iron should not exceed once a week. Administration to patients with hemodialysis-dependent chronic kidney disease is once daily, and the maximum dose should not exceed 200 mg (4 ml) of iron. Patients weighing less than 35 kg should not exceed 500 mg total iron dose. It uses intravenous infusion and can be administered up to 1,000mg (20ml) as the maximum iron once. For intravenous infusion, this drug is diluted with 0.9% sterile physiological saline solution.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Ferinject; Drug: Normal Saline Flush

Detailed Description

• Perioperative blood loss and iatrogenic hemodilution lead to postoperative anemia which correlates with infections, and poor physical function, mobility and recovery with subsequent increases in the length of hospital stay and mortality. Preoperative anemia management reduce intraoperative blood loss such as normothermia, antifibrinolytics and cell salvage are key strategies to ameliorate postoperative anemia.

• Patient screening method Off-pump coronary artery bypass (OPCAB) under median-sternotomy, or minimal invasive direct coronary bypass (MIDCAB) undertaken under median-sternotomy Among them, the selection/exclusion criteria are checked and the subjects of the study are screened. * Inclusion/ exclusion criteria **Inclusion:

  • Patients with Preoperative iron deficiency anemia Among Patients scheduled for cardiopulmonary coronary artery bypass graft under median sternotomy in cardiovascular surgery **Exclusion: - a) Patients who underwent iron correction treatment (oral, injection, blood transfusion) within 2 months prior to surgery b) Patients taking anticoagulants before surgery c) Patients taking and administering drugs that can cause bone marrow suppression, such as anticancer drugs, before surgery d) Patients with chronic liver disease and chronic kidney disease undergoing dialysis e) Patients scheduled for coronary artery bypass graft for emergency surgery f) Patients with a history of hypersensitivity reactions and side effects to iron drugs g) Minor (under 20 years old) 3) Definition of iron deficiency anemia (if all criteria a to c in the following items are satisfied)

    1. Ferritin<300mcg/L
    2. Transferrin saturation<25%
    3. Hb<12.0g/dL for women or Hb<13.0g/dL for men * The primary goal of this study was the effect of intravenous administration of ferric carboxymaltose on postoperative hemoglobin levels in patients with preoperative iron deficiency anemia among patients requiring cardiopulmonary coronary artery bypass grafting due to coronary artery disease. It is to analyze the effect compared to the control.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Young-Nam Youn; Phone Number: 82-10-9930-4522; Email: ysgs@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Contact: Young-Nam Youn; Phone Number: 82-10-9930-4522; Email: ysgs@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients aged 19 years or older
2. undergoing elective OPCAB or MIDCAB surgery with multi-vessel coronary artery disease.

Exclusion Criteria:

1. Patients who underwent iron correction treatment (oral, injection, blood transfusion) within 2 months prior to surgery
2. Patients taking anticoagulants before surgery
3. Patients taking and administering drugs that can cause bone marrow suppression, such as anticancer drugs, before surgery
4. Patients with chronic liver disease and chronic kidney disease undergoing dialysis
5. Patients scheduled for coronary artery bypass graft for emergency surgery
6. Patients with a history of hypersensitivity reactions and side effects to iron drugs
7. Minor (under 20 years old)

8. Definition of iron deficiency anemia (if all criteria a to c in the following items are satisfied)

   1. Ferritin<300mcg/L
   2. Transferrin saturation<25%
   3. Hb<12.0g/dL for women or Hb<13.0g/dL for men

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal saline	Drug: Normal Saline Flush; placebo; Other Names: placebo comparator
Experimental: Ferinject®	Drug: Ferinject; Ferric carboxymaltose injection; Other Names: Colloidal solution of the iron complex ferric carboxymaltose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total mediastinal blood loss and transfusion counts	For cost-effectiveness analysis of ferric carboxymaltose in preoperative iron treatment	At admission periods for Off-Pump Coronary Artery Bypass or Minimally Invasive Direct Coronary Artery Bypass surgery (Mean 8~9 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
blood loss in the operative day	24 hours later after surgery
amount of blood products transfused both intraoperatively and postoperatively	24 hours later after surgery
rate of surgical revision for bleeding	intraoperative
total length of intensive care unit (ICU) stay	mean 3-4 days
rate of postoperative morbidity	Participants will be followed during 1 years from operation
rate of postoperative mortality	Participants will be followed during 1 years from operation

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Young-Nam Youn, Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine

Publications and helpful links

General Publications

• Banerjee S, McCormack S. Intravenous Iron Preparations for Patients Undergoing Elective Surgery: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Mar 27. Available from http://www.ncbi.nlm.nih.gov/books/NBK545893/

Helpful Links

• Iron (Ferric) Carboxymaltose Infusion (FERINJECT®)

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2019
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 21, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hemostasis; Bleeding; Iron therapy; Coronary artery bypass surgery; Blood transfusion
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Coronary Disease; Coronary Artery Disease; Anemia, Iron-Deficiency
• Other Study ID Numbers: 4-2018-0371

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No