Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients (AGE-ANEMIA)

Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients: a Randomized Controlled Trial'

Postoperative anemia is common in cardiac surgery with cardiopulmonary bypass. Iron deficiency delays the recovery from postoperative anemia and may negatively affect the postoperative trajectory of cardiac surgery patients. The objective of the study is to determine the effect of treatment of postoperative iron deficiency anemia with intravenous iron on disability 90 days after surgery. This will be evaluated in a randomized placebo-controlled double blind two-center trial in which 310 elective cardiac surgery patients will be included.

Study Overview

• Status: Recruiting
• Conditions: Iron Deficiency Anemia
• Intervention / Treatment: Drug: Ferric Derisomaltose 100 MG/ML; Drug: Sodium chloride

Detailed Description

Rationale: Postoperative anemia is common in cardiac surgery with cardiopulmonary bypass. Iron deficiency delays the recovery from postoperative anemia and may negatively affect the postoperative trajectory of cardiac surgery patients.

Objective: To determine the effect of treatment of postoperative iron deficiency anemia (IDA) with intravenous iron (IVI) on disability 90 days after surgery.

Study design: Randomized placebo-controlled double blind two-center trial

Study population: 310 elderly patients (≥70 years) with moderate postoperative IDA on postoperative day (POD) 1 (hemoglobin (Hb) 85 - 110 g/L, ferritin concentration < 100 µg/L or iron saturation <20%) after uncomplicated elective cardiac surgery (aortic valve repair (AVR) and coronary artery bypass graft (CABG) surgery).

Intervention: Postoperative treatment with a single dose IVI (ferric derisomaltose, Monofer®, N = 155) compared to postoperative treatment with sodium chloride (NaCL) 0.9% (placebo, N = 155).

Main study endpoints: Primary endpoint is disability as measured by the 12- item World Health Organization Disability Assessment score 2.0 (WHODAS-12 at POD 90 after elective cardiac surgery. Secondary endpoints are change in patient reported outcome measures (PROMs) related to dyspnea (assessed with the Rose Dyspnea Score (RDS)) and to health-related quality of life (HRQL) (assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire) at POD 90, the number of postoperative red blood cell (RBC) transfusions, change in reticulocyte hemoglobin content (pg) from randomization to hospital discharge, Hb levels at discharge, hospital complications and days alive and out of hospital at 90 days. Lastly, the difference in functional outcomes (e.g. steep ramp or 6-minute walk test) and Hb value at POD 90 will be assessed as an exploratory endpoint.

• Study Type: Interventional
• Enrollment (Estimated): 310
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Peter Noordzij, MD, PhD; Phone Number: + 31 (0) 883203000; Email: p.noordzij@antoniusziekenhuis.nl
• Study Contact Backup: Name: Rosa Smoor, MD; Phone Number: + 31 (0) 883203000; Email: r.smoor@antoniusziekenhuis.nl

Study Locations

• Netherlands
  • Breda, Netherlands
    • Recruiting
    • Amphia Hospital
    • Contact: Thijs Rettig
  • Nieuwegein, Netherlands
    • Recruiting
    • St Antonius Hospital
    • Contact: Peter Noordzij
    • Sub-Investigator: Rosa Smoor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mentally competent with age ≥ 70 years
• Elective AVR or CABG surgery
• Expected uncomplicated postoperative trajectory, defined as:
• No inotropic agents or ventilation at time of final inclusion (POD 1)
• Expected discharge to general ward at POD 1
• Moderate postoperative IDA, defined as:
• Hb between 85 and 110 g/L and
• Ferritin <100 µg/L or
• Iron saturation (TSAT) < 20%

Exclusion Criteria:

• Medical history of iron overload/haemochromatosis
• Medical history of liver cirrhosis or ALT/AST value in blood serum triple of normal value (female patients: ALT >120, AST >105 U/L. Male patients: ALT>150, AST>135 U/L)
• Severe renal failure (eGFR<15ml/min/1.73m2)
• Recent treatment with IVI (<12 weeks prior)
• Serious or severe allergic reaction to IVI in medical history
• Severe asthma or eczema in medical history (atopic constitution)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous iron (ferric derisomaltose); The intervention consists of a single dose of ferric derisomaltose (Monofer®) 100 mg/mL solution for infusion (Monofer® is a registered product with a marketing authorization in the Netherlands (RVG number: 103070). Manufacturer: Pharmacosmos A/S, Denmark. Dutch marketing authorization holder: Cablon Medical B.V). The method of administration and dosage of the investigational medication are standard treatment. The ferric derisomaltose dose will calculated for each patient depending on body weight (20mg/kg) and diluted in 250 ml NaCl 0.9%. Treatment takes approximately 60 minutes. Vital signs of the patient will be monitored during administration of the investigational medication and for 30 minutes afterwards	Drug: Ferric Derisomaltose 100 MG/ML; Postoperative treatment with a single dose IVI (ferric derisomaltose), with a dose of 20mg/kg in approximately 60 minutes.; Other Names: Monofer
Placebo Comparator: Placebo; Single dose of sodium chloride 0.9% (250ml). Treatment takes approximately 60 minutes. Vital signs of the patient will be monitored during administration of the investigational medication and for 30 minutes afterwards	Drug: Sodium chloride; Postoperative treatment with a single dose NaCl 0.9% in approximately 60 minutes.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disability	Disability measured by the 12- item World Health Organization Disability Assessment score 2.0 (WHODAS-12). Based on the answers a disability score can be calculated. 0% is no disability and 100% is fully disabled.	90 days after elective cardiac surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient reported outcome measures (PROMs) related to dyspnea	PROMS related to dyspnea are assessed with the Rose Dyspnea Scale (RDS). Rose Dyspnea Scale scores range from 0 to 4 with higher scores indicating more dyspnea with common activities.	90 days after elective cardiac surgery
Change in patient reported outcome measures (PROMs) related to health related quality of life (HRQL)	HRQL is assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire. The TOPIC-SF is comprised of 22 items in 7 domains of health and well-being. Scores in the different domains ranges from 0 to 5, higher scores indicating diminished quality of life.	90 days after elective cardiac surgery
Red blood cell transfusions	Number of red blood cell transfusions during hospital stay	+/- 7 days after elective cardiac surgery
Change in reticulocyte hemoglobin content	Change in reticulocyte hemoglobin content from randomization to hospital discharge	+/- 7 days after elective cardiac surgery
Change in Hb level	Change in Hb level from randomization to hospital discharge	+/- 7 days after elective cardiac surgery
Postoperative complications	Postoperative complications during hospital stay	+/- 7 days after elective cardiac surgery
Days alive and out of hospital	Days alive and out of hospital	90 days after elective cardiac surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcome (exploratory endpoint)	As part of routine care, patients are offered a cardiac revalidation program supervised by a physical therapist after hospital discharge (POD 90). To assess whether patients can safely start exercising, a functional test is performed (e.g. steep ramp or 6-minute walk test). For this study, the results of these tests will be requested to assess functional capacity after surgery	+/- 90 days after elective cardiac surgery
Change in Hb level at 90 days (exploratory endpoint)	Laboratory results (i.e. Hb values if available) assessed by the treating cardiologist are requested when patients have visited the hospital during follow-up	+/- 90 days after elective cardiac surgery

Collaborators and Investigators

• Sponsor: dr. P. Noordzij
• Collaborators: Pharmacosmos A/S
• Investigators: Principal Investigator: Peter Noordzij, MD, PhD, St. Antonius Hospital

Publications and helpful links

General Publications

• Smoor RM, Rettig TCD, Vernooij LM, Groenewegen EM, van Dongen HPA, Noordzij PG. The effect of postoperative intravenous iron in anaemic, older cardiac surgery patients on disability-free survival (AGE ANEMIA study): study protocol for a multi-centre, double-blind, randomized, placebo-controlled trial. Trials. 2023 Oct 26;24(1):693. doi: 10.1186/s13063-023-07725-y.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cardiac surgery; Postoperative anemia; Intravenous iron; Postoperative disability
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia; Iron Metabolism Disorders; Anemia, Hypochromic; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia, Iron-Deficiency; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; ferric derisomaltose; Sodium Chloride
• Other Study ID Numbers: NL77442.100.21

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