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

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

Study Overview

• Status: Completed
• Conditions: Anemia; Iron Deficiency
• Intervention / Treatment: Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 1003
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • University Hospital Zurich, Institute of Anaesthesiology

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anemia; 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; 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.; Other Names: Ferinject; Eprex; Vitarubin®-superconc; Acidum folicum
Active Comparator: Iron deficiency; ferritin < 100 µg/l Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid	Drug: Erythropoietin/Ferric carboxymaltose/Vitamin B12/Folic Acid; 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.; Other Names: Ferinject; Eprex; Vitarubin®-superconc; Acidum folicum
No Intervention: Natural comparison group; Patients without anemia or iron deficiency will be observed and the same postoperative measurements performed

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation		90 days
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
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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Donat R Spahn, Prof MD, University Hospital Zurich, Institute of Anaesthesiology

Publications and helpful links

General Publications

• Rossler J, Schoenrath F, Seifert B, Kaserer A, Spahn GH, Falk V, Spahn DR. Iron deficiency is associated with higher mortality in patients undergoing cardiac surgery: a prospective study. Br J Anaesth. 2020 Jan;124(1):25-34. doi: 10.1016/j.bja.2019.09.016. Epub 2019 Oct 24.
• Spahn DR, Schoenrath F, Spahn GH, Seifert B, Stein P, Theusinger OM, Kaserer A, Hegemann I, Hofmann A, Maisano F, Falk V. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet. 2019 Jun 1;393(10187):2201-2212. doi: 10.1016/S0140-6736(18)32555-8. Epub 2019 Apr 26.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: December 16, 2013
• First Submitted That Met QC Criteria: January 6, 2014
• First Posted (Estimate): January 9, 2014

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Perioperative Care; Anemia; Cardiac surgery; Iron deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Epoetin Alfa; Folic Acid; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: IFA2012/IDCS