Investigation of the Wash-out Effect of Intravenous Iron by Cell Savers (WASH-OUT) (WASH-OUT)

Investigation of the Wash-out Effect of Intravenous Iron by Cell Savers

The study is a pilot study, which involves cardiothoracic patients. Patients, who are scheduled for elective cardiosurgical procedure, will be seen in multidisciplinary anesthesia/Patient Blood Management (PBM) clinic and screened for anemia prior to surgery. Anemic patients will eventually be treated with 500mg of ferric carboxymaltose 1 to 4 days prior to surgery. A high blood loss is expected in these procedures (>500ml). Blood is collected and re-transfused to the patient via use of cell savers/ autologous blood restoration. The investigators will examine how fast intravenous ferric carboxymaltose is stored within the iron storage cells of the body, and how much remains within the patients blood at the time point of surgery. Next, the investigators will assess the wash out effect of iron via cell salvage. The hypothesis of this trial is that ferric carboxymaltose is washed out of the collected patient's blood by cell caver usage (Wash-Out Effect).

Study Overview

• Status: Completed
• Conditions: Anemia; Anemia, Iron Deficiency; Iron Deficiency Anemia Treatment

Detailed Description

Because of the short time frame between iron therapy to procedure in cardiac surgery due to the need to perform cardiac revascularization, the investigators aim to investigate how much of the iron compound ferric carboxymaltose is being stored within the iron storage cells of the human body, and how much remains in the patient's own blood at the time point of surgery. The terminal elimination half-life time of ferric carboxymaltose is known to be approximately 7.1 to 12.1 hours, with peak serum ferritin levels at 48h to 120h after administration. When high blood loss in a surgical procedure is expected, such as in cardiosurgical procedures, the usage of autologous cell salvage, so called "Cell Saver", is considered standard, good practice. The blood that is lost during surgery is collected and after a specified blood separation wash, being retransfused in form of concentrated red blood cells.

This trial aims to examine whether Cell Saver usage might recover high molecular iron complexes such as ferric carboxymaltose lost by bleeding intraoperatively or wash out these molecules.

If amount of lost blood during surgery is too low, that Cell Saver usage would not be possible otherwise, averagely 300ml of blood from the heart-lung machine are added to the cell saver to enable the process of cell saver use.

For each participant, 7 samples will be taken. The samples include patient's blood samples and samples from cell saver compartments (Washing solution, concentrates) as well as from the heart-lung-machine, in detail:

1. arterial patient's blood, preoperative, day of procedure, prior to surgery
2. blood from the heart-lung machine, intraoperative 30 minutes prior to end of use of the heart-lung machine, day of procedure
3. Cell Saver: washed-out compounds, intraoperative, after end of use of heart-lung machine, day of procedure
4. Cell Saver: produced red blood cell concentrate, intra- or postoperative, after end of use of heart-lung machine, day of procedure
5. arterial patient's blood, postoperative, day of procedure
6. venous patient's blood, 3. day postoperative
7. venous patient's blood, 7. day postoperative

By liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) levels of ferric carboxymaltose are examined

1. in the patient's blood prior to surgery to determine the amount of ferric carboxymaltose within the patients blood prior to surgery, and after a certain time after the intravenous Infusion of ferric carboxymaltose (12-96 hours).
2. pre- and postoperatively and in cell saver compartments. If ferric carboxymaltose is detected in the washing solution of the Cell Saver System and not within the stored red blood cell concentrate, ferric carboxymaltose is washed out by the cell saver.

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

Study Locations

• Germany
  • Muenster, Germany, 48149
    • Dept. of Anesthesiology, Intensive Care and Pain Medicine, UKM

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: Non-Probability Sample

Study Population

A total of twenty-three patients undergoing elective cardiosurgical procedures (valve surgery, aortocoronary bypass or both combined) at University Hospital of Münster, Germany.

Description

Inclusion Criteria:

• scheduled cardiosurgical procedure such as valve surgery, aortocoronary bypass or both combined within 1-4 days after anesthesiological/PBM clinic
• for Group A: diagnosed anemia (hemoglobin levels below 13g/dL in men and 12g/dL in women) and iron-deficiency (transferrin saturation below 20% or ferritin serum level below 300μg/L), treatment with 500mg of ferric carboxymaltose (FerInject® 50 mg/ml, 10 ml, Vifor Pharma Group, Switzerland).

Exclusion Criteria:

• contraindication for intravenous iron therapy: severe infections, hepatocellular carcinoma, liver metastases, acute severe asthma, a simultaneous oral iron medication, another intravenous iron preparation, iron overload, chronic renal failure with regular intravenous iron substitution during dialysis treatment, age ≤18 years, pregnancy, lactation and being allergic to iron
• elevated C-reactive protein (CRP) and leukocyte levels (cut-off level for leucocytes for men was <10.9x10^3/μl and for women <12.68x10^3/μl, respectively)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Group A: anemic patients with iron treatment; For Group A anemic patients (hemoglobin levels below 13g/dL in men and 12g/dL in women) with iron deficiency (transferrin saturation below 20% or ferritin serum level below 300μg/L) are screened in the Anesthesia pre-assessment clinic 1-4 days prior to cardiosurgical procedure (valve repair/implementation, aortocoronary bypass or a combination of both) and are treated with a single intravenous dose of 500 milligrams of ferric carboxymaltose in 100ml 0,9% sodium chloride solution as iron supplementation directly (FerInject® 50 mg/ml, 10 ml, Vifor Pharma Group, Switzerland).
Group B: non-anemic patients without iron treatment; For Group B, non-anemic patients (hemoglobin levels above 13g/dL in men and 12g/dL in women) without iron deficiency (transferrin saturation above 20%, ferritin serum levels above 300μg/L) are screened in the Anesthesia pre-assessment clinic 1-4 days prior to cardiosurgical procedure (valve repair/implementation, aortocoronary bypass or both combined) and are not treated with iron supplementation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ferric Carboxymaltose levels (µg/mL)	Ferric Carboxymaltose levels in samples withdrawn from patient's blood, red blood cell concentrate of Cell Saver, heart-lung machine and washing solution prior to and after surgical procedure (µg/mL-Ferric carboxymaltose/plasma volume)	day of surgery to seven days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor red blood cell concentrates	Additional substitution of donor red blood cell concentrates	Beginning till end of surgery
Ferritin (ng/ml)	Ferritin levels before intravenous iron supplementation	prior to intravenous iron supplementation
Ferritin (ng/ml)	Ferritin levels after intravenous iron supplementation	point of intravenous iron supplementation until surgery
Ferritin (ng/ml)	Ferritin levels after intravenous iron supplementation	3 days after surgery
Ferritin (ng/ml)	Ferritin levels after intravenous iron supplementation	7 days after surgery
Hemoglobin levels (mg/dl)	Delta Hemoglobin levels between prior to IV iron substitution until surgery	prior to intravenous iron supplementation, 1 to 4 days prior to surgery
Hemoglobin levels (mg/dl)	Hemoglobin levels after surgery	3 days after surgery
Hemoglobin levels (mg/dl)	Hemoglobin levels after surgery	7 days after surgery
Intraoperative blood loss (ml)	Blood volume lost while surgical procedure	Beginning till end of surgery
Blood volume balance (ml)	Delta of intraoperatively given (infusions, transfusions) and lost (bleeding, withdrawn from heart-lung machine) volumes	Beginning till end of surgery

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Collaborators: University of Muenster, Institute of Inorganic and Analytical Chemistry
• Investigators: Study Chair: Andrea U Steinbicker, MD, MPH, Dept. of Anesthesiology, Intensive Care and Pain Medicine, University Hospital of Münster

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2019
• Primary Completion (Actual): April 29, 2021
• Study Completion (Actual): April 29, 2021

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Anemia; Iron Deficiency Anemia; Cell Saver; Intravenous Iron; Ferric Carboxymaltose; Wash Out
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia
• Other Study ID Numbers: 09-Antl-19

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