Preoperative Intravenous Ferric Carboxymaltose and Placebo in the Treatment of Patients Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety of single dose preoperative ferric carboxymaltose in the prevention of postoperative infections and blood transfusions in patients scheduled for cardiac surgery. Half of the patients will receive ferric carboxymaltose and half of the patients physiological saline solution as placebo.

Official Title
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A Phase IV Double-blind, Randomised, Parallel Group Comparison of the Efficacy and Safety of Preoperative Intravenous Ferric Carboxymaltose and Placebo in the Treatment of Patients Undergoing Elective or Urgent Cardiac Surgery

Conditions
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Coronary Artery Disease, Postoperative Complications, Aortic Valve Stenosis, Mitral Valve Disease, Aortic Aneurysm, Thoracic

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Other: Physiological saline


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients presenting with cardiac disease requiring surgical operation Open heart surgery is considered the best appropriate treatment strategy according to the current guidelines. significant three vessel disease left main disease ± single, two or three vessel disease two-vessel disease with proximal LAD stenosis coronary artery disease requiring revascularization not amenable to percutaneous coronary intervention Aortic valve disease requiring aortic valve surgery Mitral valve disease requiring surgical mitral surgery Combined surgery for revascularization and valve disease surgery of ascending aorta Have provided signed written informed consent Exclusion Criteria: Age < 35 years Patients requiring , emergency or salvage cardiac surgical operation Participation in another clinical study or treatment with another investigational product 30 days prior to randomization Moribund patient not expected to survive surgery 12 months after surgery Active malignant disease with a short life expectancy, not eligible for surgery Hemoglobin levels > 155 g/dL for women and >167 g/dl for men (upper reference limits for TYKSlab) Ferritin levels >150 ug/l for women and >400 ug/l for men. Renal dialysis therapy for chronic renal failure or severe preoperative renal impairment (eGFR<30ml/min). Study treatment can't be infused during the required time window: minimum 48 hours and maximum 21 days before the operation. Ongoing oral or parenteral iron medication at the time of randomization Iron or haemoglobin metabolism or synthesis disorders Primary or secondary hemochromatosis (in males and postmenopausal females, a serum ferritin value of over 300 ng/mL (670 pmol/L); and in premenopausal females, a serum ferritin value of over 150[17] or 200[18] ng/mL (330 or 440 pmol/L) indicates iron overload). Porphyria cutanea tarda. Liver failure (Child-Pugh class B or C). Pregnancy. Body weight less than 50kg. Ongoing antibiotic treatment other than prophylactic urine tract infection antibiotics.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled 1:1
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferric carboxymaltose<br>Preoperative 1000 mg intravenous single dose as 30 minute infusion | Drug: Ferric carboxymaltose<br>* A single dose of drug or placebo is administered preoperatively to participants<br>|
| Placebo Comparator: Placebo<br>Preoperative 100 ml saline as 30 minute infusion | Other: Physiological saline<br>* Single infusion 100 ml physiological saline infusion preoperatively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of allogeneic blood transfusion and/or nosocomial infection | Composite of transfused red blood cell units and/or nosocomial infection | 0-90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality | 0-90 days | 
| ICU/CCU days | Days in the ICU (intensive care unit) and/or CCU (cardiac care unit) | 0-90 days | 
| Perioperative myocardial infarction | MI (myocardial infarction) assessed by postoperative CK-Mbm or Troponin t levels | 3 days | 
| Length of stay | Days in hospital | 0-90 days | 
| Days on vasoactive drugs | Days on vasopressors (e.g. epinephrine, norepinephrine, milrinone etc.) | 0-90 days | 
| Ventilator free days | Days not on ventilator (intubated or non-invasive ventilation) | 0-90 days | 
| AKI (acute kidney injury) | Rate of acute renal failure | 0-90 days | 
| New onset atrial fibrillation (AF) or flutter | New AF or flutter (i.e. patient without previous history of AF/flutter) assessed from ECG-telemetry during index hospitalization or ECG-verified AF/flutter after discharge | 0-90 days | 
| Acute heart failure | Acute congestive heart failure (diagnosed by a clinician) requiring hospitalization | 90 days | 
| Worsening heart failure | Worsening to NYHA -class (New York Heart Association) III/IV or readmission for heart failure | 0-90 days | 
| Health related quality of life | Assessed with self-reporting questionnaire | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CABG, cardiac surgery, blood transfusion, intravenous iron, postoperative infection