Iron Infusion in Patients Undergoing Transcatheter Aortic Valve Implantation (IRON TAVI)

Iron Infusion in Patients Undergoing Transcatheter Aortic Valve Implantation: Study Protocol of the Randomized Controlled IRON-TAVI Trial

The aim of the open-label, randomized controlled superiority IRON TAVI trial is to investigate whether intravenous iron therapy (ferric carboxymaltose) improves Health-Related Quality of Life (HRQOL) in patients with severe aortic stenosis (AS) and iron deficiency (ID), undergoing transcatheter aortic valve implantation (TAVI).

The main questions it aims to answer are:

1. Does intravenous iron therapy improve HRQOL after TAVI in patients with severe AS and ID compared to no intravenous iron therapy (standard of care)?
2. Can intravenous iron therapy enhance exercise capacity, as measured by the 6-minute walk test, after TAVI in patients with severe AS and ID compared to no intravenous iron therapy (standard of care)?

The intervention group (receiving iron therapy after TAVI) will be compared to the control group (receiving no iron therapy after TAVI (standard of care)).

Participants will:

• Provide written informed consent

• Be randomly assigned to one of two groups:

  1. Intervention group: receiving intravenous iron therapy after TAVI (1-3 administrations in the course of 12 weeks)
  2. Control group: receiving standard of care (= no iron therapy)
• Complete assessments of HRQOL and the 6-minute walk test at baseline and week 24 after TAVI.
• During follow-up visits, other clinical parameters will be collected (i.e. laboratory status, mortality status, adverse clinical events)

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Aortic Valve Stenosis; Iron Deficiency; TAVI(Transcatheter Aortic Valve Implantation)
• Intervention / Treatment: Drug: Intravenous ferric carboxymaltose

• Study Type: Interventional
• Enrollment (Estimated): 402
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rutger-Jan Nuis, MD, PhD; Phone Number: +31614858291; Email: r.nuis@erasmusmc.nl

Study Locations

• Netherlands
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Recruiting
      • Erasmus University Medical Center
      • Contact: Rutger-Jan Nuis, MD, PhD; Phone Number: +31614858291; Email: r.nuis@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient age ≥ 65 years
• Patients with severe AS and ID undergoing successful TAVI
• ID defined as Ferritin < 100 ug/L and/or Transferrin saturation < 20%
• Ability to perform assessment of QoL (questionnaire assessment) and EC (6-MWT)
• Signed Informed Consent

Exclusion Criteria:

• Contra-indication for TAVI
• Ferritin > 400 ug/L
• Hemoglobin <5.6 mmol/L or <9 g/dL
• Hemoglobin >8.7 mmol/L or >14 g/dL in men and >8.1 mmol/L or >13 g/dL in women
• Anaemia due to known reasons other than ID and/or anticipated non-response to iron-supplementation (e.g. hemogobinopathy, bone marow disease, active cancer, unresolved active bleeding)
• Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above three times the upper limit of the normal range.
• Renal dialysis (previous, current, or planned within the next 6 months) or MDRD/CKD-EPI estimated glomerular filtration rate <15 mL/min.
• History of iron overload
• History of erythropoietin, i.v. or oral iron therapy, and blood transfusion in previous 3 months and/or such therapy planned within next 6 months
• Clinically apparent infection requiring antibiotic treatment
• Known hypersensitivity to iFCM or to any of its excipients
• Pregnancy
• Study subject participation in another TAVI related clinical study in which the primary endpoint includes mortality, hospitalization for heart failure and/or quality of life assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Receiving intravenous iron therapy (ferric carboxymaltose) after TAVI, administered in 1-3 settings over the course of 12 weeks.	Drug: Intravenous ferric carboxymaltose; The intervention involves the administration of intravenous ferric carboxymaltose (FCM) to correct iron deficiency (ID) in patients with severe aortic stenosis. FCM will be delivered in 1 to 3 settings, depending on the patient's baseline hemoglobin level, body weight, and persistence of ID after the initial administration(s): Setting-1: After successful TAVI and before hospital discharge, a maximum of 1000 milligrams of FCM will be administered.; Setting-2: A second dose of 500-1000 milligrams FCM will be administered during outpatient-clinic visit if the cumulative iron dosage has not yet been met.; Setting-3: A third dose of 500 milligrams of FCM will be administered at week 12 if ID recurs or persists during follow-up. Each dose will be infused using peripheral venous access over at least 15 minutes. The total duration of the intervention is 12 weeks, after which an endpoint outpatient follow-up assessment takes place at week 24 post-TAVI.
No Intervention: Control arm; Receiving standard of care, i.e. no intravenous iron therapy (ferric carboxymaltose) after TAVI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Health-related Quality of Life (HRQOL)	The primary endpoint is the change in HRQOL from baseline (pre-TAVI) to week-24 using the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) which has been validated in patients undergoing TAVI.	The KCCQ-23 will be filled out pre-TAVI during an outpatient or inpatient geriatric visit, or at home and will be filled out again at week-24 post-TAVI during outpatient visit or at home.
Change in 6-Minute Walk Test (6-MWT)	The co-primary endpoint is change in exercise capacity from baseline (pre-TAVI) to week-24 using the 6-MWT, which is an established objective means of evaluation exercise capacity in the TAVI population.	6-MWT is performed pre-TAVI during an outpatient or inpatient geriatric visit and will be measured again at week-24 post-TAVI during outpatient visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function (MMSE)	Cognitive function using the Mini Mental State Examination (MMSE)	Measured at week-24 post-TAVI
New York Heart Association (NYHA) functional class		Measured at week-24 post-TAVI
European Quality of Life-5 Dimensions 5 Level Utility Index (EQ-5D-5L-UI) and Visual Analog Scale (EQ-5D-VAS)	EQ5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels (no, slight, moderate, severe, and extreme problems) by which a unique health state per item is determined. These health states are converted into weighted health states (Utility Index or EQ-5D-5L-UI) by applying scores on which full health has a value of 1 and death a value of 0. The Visual Analog Scale (EQ-5D-VAS) is a self-reported score ranging from 0-100 with higher scores indicating better health.	Measured at week-24 post-TAVI
Composite of cardiovascular mortality and heart failure hospitalizations		Measured at week-24 post-TAVI
All-cause mortality		Measured at week-24 post-TAVI
Favourable quality of life (QoL)	Favourable QoL is defined as survival with a KCCQ-score ≥60 without KCCQ-decline >10 points from baseline to follow-up (week-24 post-TAVI)	Measured at baseline (pre-TAVI) and week-24 post-TAVI
Patient Global Assessment		Measured at week-24 post-TAVI

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: January 18, 2026
• First Submitted That Met QC Criteria: January 18, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 18, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Randomized Controlled Trial; Aortic Valve Stenosis; Six-Minute Walk Test; Iron Deficiency; Functional Recovery; Kansas City Cardiomyopathy Questionnaire; Health-related Quality of Life; Intravenous Iron Therapy
• Additional Relevant MeSH Terms: Aortic Valve Disease; Heart Diseases; Metabolic Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Iron Metabolism Disorders; Nutritional and Metabolic Diseases; Iron Deficiencies; Aortic Valve Stenosis; Cardiovascular Diseases
• Other Study ID Numbers: MEC-2024-0152

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No