Patient Blood Management In CARdiac sUrgical patientS (ICARUS)

Patient Blood Management In CARdiac sUrgical patientS: the ICARUS Study

Nowadays up to 40% of patients undergoing cardiac surgery receives at least 1 unit of red blood cell transfusion during surgery or during the first week after surgery. Moreover up to 40% of these patients shows an absolute or relative iron deficiency, with or without anaemia.

The objective of this study is to assess whether to implement an adequate correction of iron according to current "patients blood management" recommendations might reduce RBC transfusion requirements in patients undergoing heart surgery.

Data obtained in patients included in the study will be compared to those of a case-control population selected from patients consecutively treated at the same department in the previous 2 years.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Anemia; Iron Deficiency Anemia; Iron Deficiency Anemia Treatment; Blood Loss Anemia; Erythropoiesis Abnormal
• Intervention / Treatment: Drug: Ferric carboxymaltose; Drug: B vitamin; Drug: Folic acid

Detailed Description

Anemia is defined by the World Health Organization (WHO) as a value of hemoglobin (Hb) < 130 g/L in men and < 120 g/L in women. Anemia in surgical patients is a common and serious problem, in fact up to 40% of patients presenting for major surgery are anemic. Patients with pre-operative anemia have significantly higher rates of morbidity and mortality and are likely to receive red blood cell (RBC) transfusions. In turn, RBC are independently associated with worse outcome. Preoperative anemia mainly results from inadequate erythropoiesis owing to iron deficiency. Iron deficiency anemia (IDA) has a complex origin, including either absolute or functional iron deficiency (or iron sequestration). In absolute iron deficiency, iron stores are severely decreased, resulting in anaemia (IDA). Conversely, functional iron deficiency refers to insufficient iron mobilization despite normal or elevated iron stores (iron deficient erythropoiesis, IDE).The most rapid and simple method to correct anaemia is RBC transfusion. More than 30% of cardiac patients receives blood products in the peri-operative phase. However, blood transfusion itself is not without risk: in the setting of cardiac patients, even a single unit of blood transfused is reported to be associated to increased morbidity and mortality. Specifically, blood transfusions in cardiac surgery are associated with infections, ischemic postoperative morbidity, hospital stay, increased early and late mortality, and greater hospital costs. Preoperative correction of iron deficiency, with or without anaemia, is an integral part of the concept of the Patient Blood Management (PBM). Iron supplementation would increase the availability of iron stores and would trigger the process of erythropoiesis; the consequent relative lack of vitamin B12 and folic acid makes fundamental to restore also these 2 vitamins.

The objective of this study is to assess whether to implement an adequate correction of IDA and IDE according to current PBM recommendations might reduce RBC transfusion requirements in patients undergoing heart surgery. Data obtained in patients included in the study will be compared to those of a case-control population selected from patients consecutively treated at the same department in the previous 2 years.

• Study Type: Observational
• Enrollment (Actual): 479

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00100
    • FPG Fondazione Policlinico Gemelli IRCCS

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

All adult patients candidate to planned heart surgery in our tertiary care hospital are eligible for the study purpose.

Description

Inclusion Criteria:

- all adult patients candidate to planned heart surgery

Exclusion Criteria:

• Pregnancy
• Know allergy to iron, or B vitamin, or folic acid
• Hyperferritinemia (ferritin blood value > 300 ng/ml).
• patient's refusal

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
cases; patients who fulfill the inclusion criteria	Drug: Ferric carboxymaltose; administration of a single dose of ferric carboxymaltose in those patietns who fulfill the inclusion criteria; Other Names: ferinject; Drug: B vitamin; administration of a single dose of B vitamin in those patietns who fulfill the inclusion criteria; Drug: Folic acid; administration of a single dose of folic acid in those patietns who fulfill the inclusion criteria
controls; Patients who underwent cardiac surgery in 2019 and 2018

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients receiving RBC transfusion within post-operative day 7	Percentage of patients receiving RBC transfusion within post-operative day 7	within post operative day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb values at last postoperative control within 7 days from surgery	Hb values at last postoperative control within 7 days from surgery	within post operative day 7
length of stay in ICU	length of stay in ICU	through study completion, an average of 1 year
number of allogeneic blood products administered	number of allogeneic blood products administered	within the first 7 days post operative
duration of mechanical ventilation	duration of mechanical ventilation	within the first 7 days post operative
acute kidney injury	worsening of renal function	within the first 7 days post operative
serious adverse events	including hypersensitivity reactions	within the first 12 hours after administration
infections requiring antibiotic treatment	infections requiring antibiotic treatment	within the first 7 days post operative
mortality	patients died within the first 7 days after surgery	within the first 7 days after surgery
major adverse cardiac and cerebrovascular events	cardiogenic shock, neurological events	within the first 7 days after surgery
cost for the IDA/IDE treatment and blood product costs	cost for the IDA/IDE treatment and blood product costs	within the first 7 days after surgery

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: filippo corsi, Dr, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

General Publications

• Spahn DR, Schoenrath F, Spahn GH, Seifert B, Stein P, Theusinger OM, Kaserer A, Hegemann I, Hofmann A, Maisano F, Falk V. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet. 2019 Jun 1;393(10187):2201-2212. doi: 10.1016/S0140-6736(18)32555-8. Epub 2019 Apr 26.
• Corsi F, Pasquini A, Guerrera M, Bevilacqua F, Taccheri T, Antoniucci ME, Calabrese M, Valentini CG, Orlando N, Bartolo M, Cannetti G, Pellegrino C, Cavaliere F, Teofili L. Single shot of intravenous iron in cardiac surgery: The ICARUS study. J Clin Anesth. 2023 Feb;84:111009. doi: 10.1016/j.jclinane.2022.111009. Epub 2022 Nov 16.

Helpful Links

• Haemoglobin concentration for the diagnosis of anaemia and assesment of severity
• Perioperative Anemia Management as Part of PBM in Cardiac Surgery - A Narrative Updated Review
• The impact of anaemia and intravenous iron replacement therapy on outcomes in cardiac surgery
• Does the severity of preoperative anemia or blood transfusion have a stronger impact on long-term survival after cardiac surgery?
• A systematic analysis of global anemia burden from 1990 to 2010
• Impact of Preoperative Iron Deficiency on Blood Transfusion in Elective Cardiac Surgery
• Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function
• Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients - the study design of the LIBERAL-Trial
• Patient blood management in the cardiac surgical setting: An updated overview

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: January 31, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 2, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases; Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex
• Other Study ID Numbers: 0047459/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be shared upon reasonable request to the PI and after approval by ethic committee.

Study Data/Documents

1. Individual Participant Data Set

Drug and device information, study documents

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