Impact of Preoperative Treatment of Anemia and Iron Deficiency in Cardiac Surgery on Outcome.

Study Overview
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Brief Summary
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We are performing the above prospective randomized trial in 1'000 patients undergoing cardiac surgery. The study will answer the question of whether preoperative treatment of anemia or iron deficiency indeed improves transfusion needs (primary outcome) and important clinical outcomes (secondary outcome) in a large group of cardiac surgical patients. The list of inclusion and exclusion criteria was deliberately chosen short so that this patient group largely reflects today's clinical practice . Trial with medical product

Detailed Description
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Anemic or iron deficiency patients are randomized into treatment and placebo groups. Treatment (see below) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3). The treatment will not be disclosed to the patient or the health care workers treating the patients during and after the operation. Patients without anemia or iron deficiency will also be observed and the same postoperative measurements performed. They will serve as a natural comparison group. Treatment: Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml sodiumchloride (NaCl) over 30 min. Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po. The current transfusion and coagulation guidelines of the University Hospital of Zurich are followed in both groups identically. Postoperatively on the regular ward a Hb transfusion trigger of 80 g/L is applied

Official Title
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Impact of Preoperative Treatment of Anemia and Iron Deficiency in Cardiac Surgery on Outcome.

Conditions
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Anemia, Iron Deficiency

Intervention / Treatment
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* Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients undergoing valve- and/or coronary bypass surgery Signed patient informed consent Only patients will be enrolled who won't have an emergency surgery on the same day Exclusion criteria: Participation in another clinical trial within the last 4 weeks prior to enrollment Addiction or other disease that did not allow the patient to assess the nature, scope and possible consequences of the clinical tial Patients who do not sign the consent form or may not fully understand from inadequate knowledge of German. Patients who have not reached the age of legal majority Pregnant or lactating women Jehovah's Witnesses Patients with endocarditis Existing allergy or intolerance to ferric carboxymaltose or mannitol

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anemia<br>Hb < 120 g/L in women, Hb < 130 g/L in men Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid | Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid<br>* Treatment ) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3). Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml NaCl over 30 min. Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po.<br>* Other names: Acidum folicum;|
| Active Comparator: Iron deficiency<br>ferritin < 100 µg/l Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid | Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid<br>* Treatment ) will be given the day before the operation (day -1) or a maximum of 2 days prior to the operation (day -2) in iron deficiency patients and a maximum of 3 days prior to the operation in anemic patients (day -3). Erythropoietin alpha (Eprex, Janssen-Cilag AG, Baar) 40'000 U sc. Ferric carboxymaltose (Ferinject, Vifor (International) AG, St. Gallen) 1000 mg in 100 ml NaCl over 30 min. Vitamin B12 (Vitarubin®-superconc., Streuli Pharma AG, Uznach) 1 mg sc. Folic acid (Acidum folicum, Streuli Pharma AG, Uznach) 5 mg po.<br>* Other names: Acidum folicum;|
| No Intervention: Natural comparison group<br>Patients without anemia or iron deficiency will be observed and the same postoperative measurements performed | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red blood cell (RBC) units transfused |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients without any RBC transfusions |  | 90 days | 
| Combined allogeneic transfusions (RBC, FFP( fresh frozen plasma), platelets) |  | 90 days | 
| Length of stay in the intensive care unit (ICU) |  | 90 days | 
| Duration of mechanical ventilation |  | 90 days | 
| Acute kidney failure | RIFLE I, AKIN 2 | 7 days | 
| Major Adverse Cardiac and Cerebrovascular Events (MACCE) | Myocardial infarction, stroke, death | 90 days | 
| New atrial fibrillation |  | 90 days | 
| Infections | Pneumonia, hospital acquired Deep Sternal Wound Infection Definition of infection: rise in inflammation markers after the initial postoperative period (acute phase reaction) and requires treatment and/ or prolongs days in hospital and/or microbiological confirmation of infection | 7 days | 
| Thrombotic and thromboembolic complications (90 days) | clinical symptoms and evidence of thrombosis/ embolism in one of the following imaging methods (ultrasound, CT-scan) | 90 days | 
| Length of stay (LOS) in the hospital |  | 90 days | 
| Length of hospital stay (in comparison to median LOS published for relevant Swiss-DRGs) |  | 90 days | 
| In hospital mortality |  | 90 days | 
| 30 day and 90-day mortality |  | 90 days | 
| Costs (for blood products and pharmaceutical products related to transfusion and anemia management) | Comparison of costs for study medication versus costs for blood products and products related to transfusion | 90 days | 
| Perioperative Hb concentrations |  | 90 days | 
| Calculated RBC and blood loss |  | 90 days | 
| Comparison of the treatment and placebo groups with the natural comparison group |  | 90 days | 
| Safety and tolerance of administered study drug and placebo | Comparison of all serious adverse events between study drug group and placebo group | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Iron deficiency, Cardiac surgery, Perioperative Care