Preoperative Intravenous Ferric Carboxymaltose and Placebo in the Treatment of Patients Undergoing Cardiac Surgery (PREFER-CABG)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Postoperative Complications; Aortic Valve Stenosis; Aortic Aneurysm, Thoracic; Mitral Valve Disease
• Intervention / Treatment: Drug: Ferric carboxymaltose; Other: Physiological saline

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jarmo M Gunn, adj. professor; Phone Number: +35823130000; Email: jarmo.gunn@tyks.fi
• Study Contact Backup: Name: Tuija Vasankari, RN; Phone Number: +35823130000

Study Locations

• Finland
  • Turku, Finland, 20521
    • Recruiting
    • Turku University Hospital
    • Contact: Jarmo M Gunn, PhD; Phone Number: +35823130548; Email: jarmo.gunn@tyks.fi
    • Contact: Tuija Vasankari, RN; Phone Number: +35823130000; Email: tuija.vasankari@tyks.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Patients presenting with cardiac disease requiring surgical operation

2. 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
3. Have provided signed written informed consent

Exclusion Criteria:

1. Age < 35 years
2. Patients requiring , emergency or salvage cardiac surgical operation
3. Participation in another clinical study or treatment with another investigational product 30 days prior to randomization
4. Moribund patient not expected to survive surgery 12 months after surgery
5. Active malignant disease with a short life expectancy, not eligible for surgery
6. Hemoglobin levels > 155 g/dL for women and >167 g/dl for men (upper reference limits for TYKSlab)
7. Ferritin levels >150 ug/l for women and >400 ug/l for men.
8. Renal dialysis therapy for chronic renal failure or severe preoperative renal impairment (eGFR<30ml/min).
9. Study treatment can't be infused during the required time window: minimum 48 hours and maximum 21 days before the operation.
10. Ongoing oral or parenteral iron medication at the time of randomization
11. Iron or haemoglobin metabolism or synthesis disorders
12. 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).
13. Porphyria cutanea tarda.
14. Liver failure (Child-Pugh class B or C).
15. Pregnancy.
16. Body weight less than 50kg.
17. Ongoing antibiotic treatment other than prophylactic urine tract infection antibiotics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferric carboxymaltose; Preoperative 1000 mg intravenous single dose as 30 minute infusion	Drug: Ferric carboxymaltose; A single dose of drug or placebo is administered preoperatively to participants
PLACEBO_COMPARATOR: Placebo; Preoperative 100 ml saline as 30 minute infusion	Other: Physiological saline; Single infusion 100 ml physiological saline infusion preoperatively

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: Vifor Pharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 2, 2018
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (ACTUAL): June 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: cardiac surgery; CABG; blood transfusion; intravenous iron; postoperative infection
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Coronary Disease; Aortic Diseases; Coronary Artery Disease; Aortic Valve Stenosis; Postoperative Complications; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Thoracic
• Other Study ID Numbers: PREFER-CPB01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No