Postoperative Replacement of Intraoperative Iron Losses (POREIIL)

• ClinicalTrials.gov Identifier: NCT03680456
• Recruitment Status: Not yet recruiting
• First Posted: September 21, 2018
• Last Update Posted: January 29, 2020
• Sponsor: Kepler University Hospital
• Information provided by (Responsible Party): Nina Pauker, MD, Kepler University Hospital

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Blood Loss Anemia	Drug: Ferric carboxymaltose; Drug: Crystalloid	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: interventional randomized doubleblind, Placebo controlled
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Postoperative Replacement of Intraoperative Iron Losses
• Estimated Study Start Date: February 1, 2020
• Estimated Primary Completion Date: October 31, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

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 Name: Ferinject
Placebo Comparator: Placebo; Natriumchlorid is the placebo	Drug: Crystalloid; an equivalent volume dose of Natriumchlorid is administered; Other Name: Natriumchlorid

Outcome Measures

Primary Outcome Measures :

1. Hemoglobin Level [ Time Frame: 30days ]
   Hemoglobin in g/dl

Secondary Outcome Measures :

1. Number of RBCs [ Time Frame: 30days ]
   Number of Units of Red Blood Cell transfusions
2. 10 Feet Walking test [ Time Frame: day 7 and 30 post randomization ]
   ability to walk 10 feet or across the room
3. 6min Walking Test [ Time Frame: preoperative day, day 7 and 30 ]
   The distance ist measured which the Patient is able to walk in 6 min
4. Infection [ Time Frame: 30 Days ]
   Number of severe Sepsis or wound infection due to SSC Guidelines and Sofa-Score
5. MI [ Time Frame: 30days ]
   myocardial infarction is diagnosed du to ECG, Troponin T and clinical signs and symptoms for myocardial infarction e.g. chest pain
6. AKI [ Time Frame: 30 days ]
   acute kidney injury due to KDIGO criteria
7. Stroke [ Time Frame: 30days ]
   numbers of stroke (e.b. subarachnoid hemorrhage and others)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Nina Pauker, Dr.; 00435768083 ext 78168; nina.pauker@kepleruniklinikum.at

Contact: Jens Meier, Prof; 00435768083 ext 2158; jens.meier@kepleruniklinikum.at

Locations

Austria

Universitätsklinik für Anästhesie und Intensivmedizin

Linz, Austria

Contact: Jens Meier, MD jens.meier@kepleruniklinikum.at

Sub-Investigator: Bernhard Eichler, MD

Sub-Investigator: Roxanne Brooks, MD

Sponsors and Collaborators

Kepler University Hospital

Investigators

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

More Information

• Responsible Party: Nina Pauker, MD, Principal Investigator, Kepler University Hospital
• ClinicalTrials.gov Identifier: NCT03680456
• Other Study ID Numbers: TPL107
• First Posted: September 21, 2018
• Last Update Posted: January 29, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Nina Pauker, MD, Kepler University Hospital:

Anemia; Ferric carboxymaltose; intravenous iron; intraoperative blood loss; patient blood management; Red blood cell transfusion; postoperative iron replacement

Additional relevant MeSH terms:

Hemorrhage; Pathologic Processes