Effect of Perioperative Iron Isomaltoside 1000 Administration on Transfusion Requirements in Patients Undergoing Complex Valvular Heart Surgery: a Randomized Clinical Trial

In complex cardiac surgery with prolonged cardiopulmonary bypass, allogeneic blood products transfusions are often necessary to control intraoperative and postoperative bleeding. Furthermore, approximately 50% of all patients undergoing cardiac surgery are anemic before surgery, and patients with normal hemoglobin level may become anemic during and/or after surgery. Perioperative transfusion carries risks far beyond transmission of infection and has been demonstrated to be associated with adverse outcomes related to postoperative pulmonary complications, decreased renal function and increased mortality. Thus, the important of blood conservation stratigies to minimize transfusion is being increasingly emphasized. In recent trial by Johansson and colleagues, they concluded that the perioperative administration of intravenous iron isomaltoside 1000 increased the hemoglobin level and prevented anemia 4 weeks after cardiac surgery. Therefore, perioperative iron isomaltoside 1000 administration among the patients undergoing complex valvular heart surgery could reduce not only the perioperative allogeneic transfusion but also the incidence of postoperative adverse events. The aim of this study is to examine the effect of perioperative iron isomaltoside 1000 administration on transfusion requirements in patients undergoing complex valvular heart surgery.

Study Overview

• Status: Completed
• Conditions: Complex Valvular Heart Surgery
• Intervention / Treatment: Drug: iron isomaltoside 1000 (Monofer®); Drug: normal saline 100 ml

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Department of Thoracic and Cardiovascular Surgery, Cardiovascular Research Institute, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. the patients undergoing redo cardiac surgery or complex valvular heart surgery with cardiopulmonary bypass
2. tha age ≥19 yrs old.
3. the patients who are willing to provide written informed consent

Exclusion Criteria:

1. having preoperative anemia (Hb <9 g/dl for women, Hb <10 g/dl for men)
2. preoperative erythropoietin treatment within four weeks before surgery
3. redo cardiac operation due to preoperative paravalvular leakage
4. known hypersensitivity to any excipients in the investigational drug products
5. aplastic anemia
6. the patients who stay more than 48 hours in the intensive care unit preoperatively due to heart failure or other major complication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IV iron; The patients will receive iron isomaltoside 1000 (Monofer®) as an i.v. infusion of 1000 mg (diluted with normal saline, 10 mg/ml) twice; 3 days before surgery and 3 days after surgery. They will receive iron isomaltoside 1000 (Monofer®) 1000 mg over 15 min.	Drug: iron isomaltoside 1000 (Monofer®); The patients will receive iron isomaltoside 1000 (Monofer®) as an i.v. infusion of 1000 mg (diluted with normal saline, 10 mg/ml) twice; 3 days before surgery and 3 days after surgery. They will receive iron isomaltoside 1000 (Monofer®) 1000 mg over 15 min.
PLACEBO_COMPARATOR: Control; The patients will receive normal saline 100 ml as an i.v. infusion twice; 3 days before surgery and 3 days after surgery. They will receive normal saline 100 ml over 15 min.	Drug: normal saline 100 ml; The patients will receive normal saline 100 ml as an i.v. infusion twice; 3 days before surgery and 3 days after surgery. They will receive normal saline 100 ml over 15 min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of patients who need blood transfusion	Investigator will assess the number of patients in each group who will need blood transfusion during hospital stays, and evaluate the effect of iron isomaltoside 1000 (Monofer®) on perioperative blood transfusion.	patients will be followed for the duration of hospital stay, an expected average of 10 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of patients who will experience postoperative adverse events	Investigator will assess the number of patients in each group who will experience postoperative adverse events (death, atrial fibrillation, reoperation, wound infection, acute kidney injury, permanent stroke, prolonged mechanical ventilation or postoperative myocardial infarction) within the first 20 days after surgery, and evaluate the effect of iron isomaltoside 1000 (Monofer®) on the occurrence of any postoperative adverse events.	within the first 20 days after surgery. (plus or minus 3 days)
the plasma hepcidin concentrations of patients	Investigator will assess the plasma hepcidin concentrations before the investigational drug i.v. infusion; 3 days before surgery and 3 days after surgery, and evaluate the association between the plasma hepcidin concentrations and the effect of iron isomaltoside 1000 (Monofer®) or the occurrence of any postoperative adverse events.	before the investigational drug i.v. infusion; 3 days before surgery and 3 days after surgery
the plasma EPO (erythropoietin) concentrations of patients	Investigator will assess the plasma EPO concentrations before the investigational drug i.v. infusion; 3 days before surgery and 3 days after surgery, and evaluate the association between the plasma EPO concentrations and the effect of iron isomaltoside 1000 (Monofer®) or the occurrence of any postoperative adverse events.	before the investigational drug i.v. infusion; 3 days before surgery and 3 days after surgery

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Lee SH, Shim JK, Soh S, Song JW, Chang BC, Lee S, Kwak YL. The effect of perioperative intravenously administered iron isomaltoside 1000 (Monofer(R)) on transfusion requirements for patients undergoing complex valvular heart surgery: study protocol for a randomized controlled trial. Trials. 2018 Jul 4;19(1):350. doi: 10.1186/s13063-018-2545-3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2016
• Primary Completion (ACTUAL): May 7, 2020
• Study Completion (ACTUAL): May 7, 2020

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (ESTIMATE): August 11, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: 4-2016-0502

Plan for Individual participant data (IPD)

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