Postoperative Replacement of Intraoperative Iron Losses (POREIIL)

By performing a randomized, blinded placebo controlled exploratory trial we speculate that replacement of perioperative, bleeding-induced iron losses with ferric carboxymaltose immediately after the surgical procedure can replenish iron with increased hemoglobin levels and reduce the amount of pRBCs transfused in the postoperative period (30 days post surgery).

Study Overview

• Status: Recruiting
• Conditions: Blood Loss Anemia
• Intervention / Treatment: Drug: Ferric carboxymaltose; Drug: Crystalloid

Detailed Description

In the last few years, state of the art Patient Blood Management (PBM programs have been gaining worldwide attention. This may be attributed to the significant improvements in patient outcomes that follow adequate preoperative preparation and intraoperative optimization of the circulating red cell mass.

The first pillar of PBM (pre-, intra-, and postoperative optimization of red cell mass by means other than red cell transfusions including intravenous iron and erythropoietin stimulating agents) can meet significant barriers and might be difficult to implement. In daily clinical practice, timely identification and treatment of preoperative anemia is difficult to organize due to structural and behavioral constraints. Therefore, today, there are still a striking number of patients who are admitted for surgery without adequate preoperative treatment of anemia regardless of its causes. Notably, even for this patient population, it has been demonstrated by experimental and larger observational data that postoperative application of intravenous iron could help to reduce perioperative transfusions by restoring red cell mass. The complete potential of perioperative intravenous iron therapy has yet to identified, including improvements such as early mobility and other improved outcomes. Furthermore, a substantial number of patients are not included in preoperative red cell mass optimization, since the preoperative hemoglobin concentration is either high enough in terms of the thresholds of the World Health Organization (♂ 13 g/dl and ♀ 12 g/dl), or borderline (mild) anemia is diagnosed and no treatment is offered. These patients may be prone to substantial intraoperative blood losses, and as a consequence might suffer from postoperative iron restricted anemia. In fact, there are a remarkable number of patients that have adequate hemoglobin concentrations preoperatively, but ultimately develop anemia with iron deficiency postoperatively due to significant intraoperative bleeding. Data from ICU patients' with postoperative iron deficiency has significant impact on outcome including postoperative fatigue, and consequently a prolonged healing process.

Although this problem is common, current PBM strategies are in need of validation of one of the PBM guidelines: postoperative replacement of blood loss with resultant iron losses in patients without preoperative anemia thus avoiding exposure to allogeneic transfusions in this population. The untested hypothesis is that this approach could improve postoperative outcomes including mobilization. Based on a recent publication one might surmise that it is not (only) postoperative anemia, but rather untreated iron deficiency, that is responsible for a delay in postoperative mobilization and recovery. It is therefore the aim of the proposal presented to describe an additional approach, in which perioperative, surgical blood loss iron losses are replaced immediately following the surgical procedure in patients that did not receive iron preoperatively due to normal or minor reduction in hemoglobin concentrations (red cell mass). This replacement may take place in either the postoperative anesthesia care unit or in the ICU, Although preoperative treatment of iron deficiency anemia is widely considered the most important domain of perioperative iron therapy, the additional post-operative replacement is as useful as preoperative preparation and seems to be more convenient to implement.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Roxane Brooks, Dr.; Phone Number: 78148 00435768083; Email: roxane.brooks@kepleruniklinikum.at
• Study Contact Backup: Name: Jens Meier, Prof; Phone Number: 2158 00435768083; Email: jens.meier@kepleruniklinikum.at

Study Locations

• Austria
  • Linz, Austria
    • Recruiting
    • Universitätsklinik für Anästhesie und Intensivmedizin
    • Contact: Jens Meier, MD; Email: jens.meier@kepleruniklinikum.at
    • Sub-Investigator: Bernhard Eichler, MD
    • Sub-Investigator: Roxanne Brooks, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients undergoing non-emergency

  - cardiac surgery - obstetric surgery - intra-abdominal surgery

• preoperative Hb (during the premedication visit):

  • ♂: Hb>12.5g/dl
  • ♀: Hb>11.5g/dl

• postoperative Hb (immediately after surgical procedure in the recovery room):

  - 2 g/dl below preoperative Hb concentration

• age ≥ 18 years
• Admission to intensive care unit or post-anesthesia care unit
• Able to sign consent for the trial

Exclusion Criteria:

• age < 18 years
• emergency surgery
• perioperative application of iron and/or erythropoietin
• intraoperative transfusion of allogeneic erythrocytes
• known hemochromatosis
• known allergic reaction linked to iron medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; due to postoperative Hemoglobin Level intravenous iron Ferriccarboxymaltose is Infuses, dosage is based on the Ganzoni-Algorithm	Drug: Ferric carboxymaltose; maximum of 750mg in U.S. is given, maximum of 1000mg in EU; Other Names: Ferinject
Placebo Comparator: Placebo; Natriumchlorid is the placebo	Drug: Crystalloid; an equivalent volume dose of Natriumchlorid is administered; Other Names: Natriumchlorid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin Level	Hemoglobin in g/dl	30days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of RBCs	Number of Units of Red Blood Cell transfusions	30days
10 Feet Walking test	ability to walk 10 feet or across the room	day 7 and 30 post randomization
6min Walking Test	The distance ist measured which the Patient is able to walk in 6 min	preoperative day, day 7 and 30
Infection	Number of severe Sepsis or wound infection due to SSC Guidelines and Sofa-Score	30 Days
MI	myocardial infarction is diagnosed du to ECG, Troponin T and clinical signs and symptoms for myocardial infarction e.g. chest pain	30days
AKI	acute kidney injury due to KDIGO criteria	30 days
Stroke	numbers of stroke (e.b. subarachnoid hemorrhage and others)	30days

Collaborators and Investigators

• Sponsor: Kepler University Hospital
• Investigators: Study Director: Jens Meier, Prof, Kepler University Hospital, JKU Linz

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2020
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 20, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Anemia; Red blood cell transfusion; patient blood management; Ferric carboxymaltose; intravenous iron; intraoperative blood loss; postoperative iron replacement
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: TPL107

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
• product manufactured in and exported from the U.S.: No