The effect of perioperative intravenously administered iron isomaltoside 1000 (Monofer®) on transfusion requirements for patients undergoing complex valvular heart surgery: study protocol for a randomized controlled trial

Abstract

Background: Anemia is a frequent complication after cardiac surgery especially following reoperation due to previous prosthetic valve failure or multiple valve surgery (including combined coronary artery bypass grafting). This trial explores whether intravenously administered iron isomaltoside 1000 (Monofer®) results in better clinical outcomes in patients undergoing complex heart valve surgery who are expected to receive transfusion.

Methods/design: In this prospective, single-center, double-blinded, randomized controlled trial, 214 patients undergoing reoperation or multiple valve surgery are randomly allocated to either the iron isomaltoside 1000 (IVFe) or the control group from August 2016 to August 2018. The IVFe group receives iron isomaltoside 1000 mg (maximum dose 20 mg/kg) intravenously 3 days before and after the surgery. The control group receives an equivalent volume of normal saline. The primary endpoint is transfusion requirement (more than 1 unit of packed erythrocytes) for postoperative care until discharge and secondary endpoint are major complications, such as delayed ventilator therapy, acute kidney injury, and mortality. Reticulocyte count, plasma hepcidin, iron profiles (serum iron, serum ferritin, total iron-binding capacity, transferrin, transferrin saturation), coagulation profiles, urinary analysis, and chemical profiles are measured for three preoperative baseline-data days and just before surgery, except for hepcidin. After surgery, daily routine basic laboratory tests are measured just before discharge and reticulocyte count, iron profiles, and hepcidin are repeatedly checked for three postoperative days.

Discussions: From our study, we can clarify the following points: the first is the perioperative IVFe effect on the demand for transfusion, and clinical outcomes in reoperation or complex valve surgery and the second is the role of hepcidin in the effect of IVFe on the hemoglobin level increase.

Trial registration: ClinicalTrials.gov , Identifier: NCT02862665 . Registered on August 2016.

Keywords: Anemia; Complex valvular heart surgery; Iron isomaltoside 1000; Transfusion.

Conflict of interest statement

Ethics approval and consent to participate

The trial protocol and related documents were approved by the competent authorities and the Institutional Review Board (IRB) of the University of Yonsei (approval number: 4-2016-0502). The trial was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. Informed consent was obtained in writing prior to any trial-related activities.

Consent for publication

I (Seung Hyun Lee) give my consent for information about myself to be published in Trials. I understand that the information will be published without my name attached, but that full anonymity cannot be guaranteed. I understand that the text and any pictures or videos published in the article will be freely available on the Internet and may be seen by the general public. The pictures, videos and text may also appear on other websites or in print, may be translated into other languages or used for commercial purposes. I have been offered the opportunity to read the manuscript.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Schematic of study design