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

• ClinicalTrials.gov Identifier: NCT03574311
• Recruitment Status: Recruiting
• First Posted: June 29, 2018
• Last Update Posted: April 20, 2021
• Sponsor: Turku University Hospital
• Collaborator: Vifor Pharma
• Information provided by (Responsible Party): Turku University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease; Postoperative Complications; Aortic Valve Stenosis; Mitral Valve Disease; Aortic Aneurysm, Thoracic	Drug: Ferric carboxymaltose; Other: Physiological saline	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized controlled 1:1
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Double blinding, study drug administration by separate staff blinded from participant and investigators
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: October 2, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of allogeneic blood transfusion and/or nosocomial infection [ Time Frame: 0-90 days ]
   Composite of transfused red blood cell units and/or nosocomial infection

Secondary Outcome Measures :

1. Mortality [ Time Frame: 0-90 days ]
   All-cause mortality
2. ICU/CCU days [ Time Frame: 0-90 days ]
   Days in the ICU (intensive care unit) and/or CCU (cardiac care unit)
3. Perioperative myocardial infarction [ Time Frame: 3 days ]
   MI (myocardial infarction) assessed by postoperative CK-Mbm or Troponin t levels
4. Length of stay [ Time Frame: 0-90 days ]
   Days in hospital
5. Days on vasoactive drugs [ Time Frame: 0-90 days ]
   Days on vasopressors (e.g. epinephrine, norepinephrine, milrinone etc.)
6. Ventilator free days [ Time Frame: 0-90 days ]
   Days not on ventilator (intubated or non-invasive ventilation)
7. AKI (acute kidney injury) [ Time Frame: 0-90 days ]
   Rate of acute renal failure
8. New onset atrial fibrillation (AF) or flutter [ Time Frame: 0-90 days ]
   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
9. Acute heart failure [ Time Frame: 90 days ]
   Acute congestive heart failure (diagnosed by a clinician) requiring hospitalization
10. Worsening heart failure [ Time Frame: 0-90 days ]
    Worsening to NYHA -class (New York Heart Association) III/IV or readmission for heart failure
11. Health related quality of life [ Time Frame: 12 months ]
    Assessed with self-reporting questionnaire

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jarmo M Gunn, adj. professor; +35823130000; jarmo.gunn@tyks.fi

Contact: Tuija Vasankari, RN; +35823130000

Locations

Finland

Turku University Hospital; Recruiting

Turku, Finland, 20521

Contact: Jarmo M Gunn, PhD +35823130548 jarmo.gunn@tyks.fi

Contact: Tuija Vasankari, RN +35823130000 tuija.vasankari@tyks.fi

Sponsors and Collaborators

Turku University Hospital

Vifor Pharma

More Information

• Responsible Party: Turku University Hospital
• ClinicalTrials.gov Identifier: NCT03574311
• Other Study ID Numbers: PREFER-CPB01
• First Posted: June 29, 2018
• Last Update Posted: April 20, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Turku University Hospital:

CABG; cardiac surgery; blood transfusion; intravenous iron; postoperative infection

Additional relevant MeSH terms:

Coronary Artery Disease; Aneurysm; Aortic Aneurysm; Aortic Valve Stenosis; Aortic Aneurysm, Thoracic; Postoperative Complications; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Aortic Diseases; Pathologic Processes; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction