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

Study Overview
=================
Brief Summary
-----------------
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

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.

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

Conditions
-----------------
Anemia, Iron Deficiency

Intervention / Treatment
-----------------
* Drug: Ferric carboxymaltose
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cardiac surgery, ferric carboxymaltose, anemia, transfusion