Effects of Ferinject® on Anemia and Transfusion Rates After Cardiac Surgery (FCAACS)

Ferric Carboxymaltose (Ferinject®) Administered After Cardiac Surgery: (FCAACS) Effects On Correction Of Anemia And Transfusion Rates: A Prospective Randomized Controlled Trial

Several studies using new forms of intravenous iron showed that it is effective in treating perioperative anemia in orthopedic and digestive surgery. Effects of ferric carboxymaltose have not been assessed in the settings of cardiac surgery.

This study will compare ferric carboxymaltose to placebo in a randomized trial design where ferric carboxymaltose / placebo will be administered in the postoperative period (Day 1) after cardiac surgery. A total sample size of 200 patients (100 per group) will be needed.

The FCAACS trial will assess the impact of administering intravenous iron (Ferric carboxymaltose) after cardiac surgery with cardiopulmonary bypass (CPB) on the:

• incidence of postoperative anemia
• incidence of postoperative transfusion
• incidence of complications related to intravenous iron

All the surgeries will be performed by the same surgical team and follow-up will be ensured by the same Cardiac Surgery Unit (CSU) team according to department's standard protocols.

Participants in the Ferric carboxymaltose group will receive 1g of Ferric carboxymaltose diluted in 100 mL of IV isotonic serum saline, whereas participants in the Placebo group will receive 100 mL of IV Placebo

Study Overview

• Status: Completed
• Conditions: Anemia, Iron Deficiency
• Intervention / Treatment: Drug: Ferric carboxymaltose; Drug: Placebo

Detailed Description

Anemia is very common in the perioperative of major surgery affecting about 30% of patients preoperatively and more than 80% postoperatively. Anemia is an independent risk factor of morbi-mortality.

Iron deficiency is the first cause of anemia. Physiological reserves of iron are not important, and the correction of anemia after hemorrhage is very slow. Hence, it takes 90 days to return to 80% of the basic Hb level after a blood donation of 500ml, and more than 150 days (almost 6 months), if one is deficient in iron. This is why iron is used to correct anemia that occurs after bleeding. There are two routes for iron administration: oral and intravenous.

Gastrointestinal absorption of iron is limited to 10-15 mg/d even when ingested doses are increased. This absorption is decreased in the presence of an inflammatory state, which is very common in the postoperative period.

The intravenous route allows the delivery of significantly higher doses of iron (up to 1000 mg in 1 infusion), without any limitation related to absorption. This is why it is interesting to administer it perioperatively where the expected delays are short.

There are currently new intravenous iron formulations that have two advantages: a shorter intravenous injection time and a higher maximum injectable dose per infusion. These new forms are risk-free, with no serious allergy described so far in the literature.

Several studies using new forms of intravenous iron showed that it is effective in treating perioperative anemia in orthopedic and digestive surgery. Effects of ferric carboxymaltose have not been assessed in the settings of cardiac surgery.

To assess the impact of ferric carboxymaltose in cardiac surgery, it will be compared to placebo in a randomized trial design, where ferric carboxymaltose / placebo will be administered in the postoperative period. Ferric carboxymaltose / placebo will be an add-on to the current treatment of patients in the postoperative period of cardiac surgery, the group that will be receiving placebo reflects the current management of the patients in these settings.

The FCAACS trial will assess the impact of administering intravenous iron (Ferric carboxymaltose) after cardiac surgery with cardiopulmonary bypass (CPB) on the:

• incidence of postoperative anemia
• incidence of postoperative transfusion
• incidence of complications related to intravenous iron

FCAACS will be a parallel group randomized trial, with a 2-group design and no crossover. Allocation ratio will be 1/1, in an equivalence framework. A total sample size of 200 patients (100 per group) will be needed.

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 4

Contacts and Locations

Study Locations

• Lebanon
  • Beirut, Lebanon, 166830
    • Hotel Dieu de France Hospital

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:

• Adult patients admitted for elective cardiac surgery under cardiopulmonary bypass, with no exclusion criteria, and having signed an informed consent, will be enrolled in the study.

Exclusion Criteria:

• Patients < 18 years
• Urgent surgery
• Off-pump cardiac surgery
• Redo cardiac surgery
• Preoperative anemia (Hb < 10g/l or Ht < 30%)
• Transfusion within 72h preoperatively
• Pregnancy
• History of asthma or other specific allergies
• History of allergy to iron
• Acute infection
• Hepatic insufficiency
• Renal insufficiency (creatinine Clearance < 30ml/min)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ferric Carboxymaltose group; Ferric carboxymaltose group will receive 1g of Ferric carboxymaltose at day 1 following cardiac surgery	Drug: Ferric carboxymaltose; 1g of Ferric carboxymaltose diluted in 100 mL of IV isotonic serum saline at day 1 following surgery; Other Names: Ferinject®
Placebo Comparator: Placebo group; Placebo group will receive 100 mL of IV isotonic serum saline at day 1 following cardiac surgery	Drug: Placebo; 100 mL of IV isotonic serum saline at day 1 following surgery; Other Names: Serum saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in level of hemoglobin (g/dL) from preoperative until day 30 after surgery	mean ± standard deviation, measured at 5 timepoints	Preoperative (Day -2), Day 0 [CSU admission], Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in Hematocrit from preoperative until day 30 after surgery (final value)	mean ± standard deviation, measured at 5 timepoints	Preoperative (Day -2), Day 0 [CSU admission], Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30
Change in Reticulocytes count from preoperative until day 30 after surgery (final value)	measured at 4 timepoints	Preoperative (Day -2), Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30
Change in Percentage of transferrin from preoperative until day 30 after surgery (final value)	measured at 4 timepoints	Preoperative (Day -2), Day 1 [CSU, before study drug], Day 5 [hospital discharge], Day 30
Change in Ferritin from preoperative until day 30 after surgery (final value)	measured at 4 timepoints	Preoperative (Day -2), Day 1 [CSU, before study drug], Day 5 [hospital discharge], Day 30
Number of red cell packs transfused (final value)	mean ± standard deviation, measured at 3 timepoints	Day 1, Day 5,and Day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total bleeding (mL) until drain removal (final value)	mean ± standard deviation	From Day 0 until Day 2
Time to tracheal tube removal, measured in hours (final value)	mean ± standard deviation	From Hour 0 until Hour 6 (on average, until tracheal tube removal)
Length of stay in the CSU measured in Days	median and interquartile range	From Day 0 [CSU admission] until Day 2 [on overage, CSU discharge]
Surgical exploration for bleeding (Boolean, proportion)	Proportion, with 95% confidence interval	From Day 0 [CSU admission] until Day 2 [on overage, CSU discharge]
Complications related to administration of Ferric carboxymaltose (proportion)	Proportion, with 95% confidence interval	From Day 0 until Day 30

Collaborators and Investigators

• Sponsor: St Joseph University, Beirut, Lebanon
• Collaborators: Saint-Joseph University; Vifor Pharma
• Investigators: Principal Investigator: Samia Madi-Jebara, Pr, St Joseph University Beirut

Publications and helpful links

General Publications

• Houry M, Tohme J, Sleilaty G, Jabbour K, Bou Gebrael W, Jebara V, Madi-Jebara S. Effects of ferric carboxymaltose on hemoglobin level after cardiac surgery: A randomized controlled trial. Anaesth Crit Care Pain Med. 2022 Nov 11;42(1):101171. doi: 10.1016/j.accpm.2022.101171. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2018
• Primary Completion (Actual): December 9, 2020
• Study Completion (Actual): January 2, 2021

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 8, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: cardiac surgery; anemia; transfusion; ferric carboxymaltose
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia
• Other Study ID Numbers: CEHDF 1050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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