IV versus oral iron for people with heart failure and low iron

IRONICA: IRON Repletion in Congestive Heart Failure - A Randomized Controlled Trial Comparing Oral Versus IV Approaches

This will test whether a one-time IV iron infusion or daily oral iron helps adults with heart failure and low iron (TSAT <20%) improve walking distance, symptoms, and quality of life over 24 weeks.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Western Kentucky Heart and Lung Research Foundation and Educational Trust (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Bowling Green, Kentucky)
• Trial ID: NCT07053475 on ClinicalTrials.gov

What this trial studies

Adults with HFrEF or HFpEF and transferrin saturation below 20% are randomly assigned to receive either IV ferric carboxymaltose or oral ferrous sulfate. The main outcome is change in 6-minute walk distance at 24 weeks, with secondary outcomes including symptoms, quality of life, safety, hospital readmissions, and mortality. Participants must meet hemoglobin and NT-proBNP thresholds, be NYHA class II–IV, stable on heart-failure therapy, and ambulatory for walk testing. The trial is conducted at a single center with scheduled baseline and follow-up visits including laboratory monitoring and adverse event surveillance.

Who should consider this trial

Good fit: Adults (≥18) with HFrEF (EF ≤40%) or HFpEF (EF ≥50–55 with evidence of diastolic dysfunction), NYHA class II–IV, TSAT <20%, hemoglobin within the study-specified range, stable on heart-failure therapy, and ambulatory are ideal candidates.

Not a fit: People without iron deficiency (TSAT ≥20%), with hemoglobin outside the allowed range, non-ambulatory patients, or those unable to attend in-person visits are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, the results could show which iron treatment helps people with heart failure and iron deficiency walk farther, feel better, and have fewer hospital visits.

How similar studies have performed: Prior randomized trials in HFrEF have shown benefits from IV ferric carboxymaltose for symptoms and exercise capacity while oral iron is generally less effective, though robust data in HFpEF are limited.

Eligibility criteria

Inclusion Criteria:

* Age ≥18 years
* BMI ≥18.0 kg/m²
* Hemoglobin:

\> 9 g/dL and \<14 g/dL for men \> 9 g/dL and \<13 g/dL for women

* Diagnosed with Congestive Heart failure:

HFrEF: EF ≤40% in any recent echocardiogram HFpEF: EF ≥50-55% without any prior EF ≤40%, and evidence of diastolic dysfunction per ASE/EACVI 2023 criteria-defined as either grade ≥2 or ≥2 supporting echo parameters (septal e' \<7 cm/sec or lateral e' \<10 cm/sec, E/e' ≥15, TR velocity \>2.8 m/s, LA volume index ≥34 mL/m², LV septal or posterior wall thickness ≥1.2 cm, or LA area ≥20 cm² / diameter ≥3.8 cm.

* Documented elevated NT-proBNP based on BMI and rhythm:

BMI \<35: ≥220 pg/mL (NSR) or ≥660 pg/mL (A-Fib) BMI ≥35: ≥125 pg/mL (NSR) or ≥375 pg/mL (A-Fib)

* NYHA Class II-IV
* Transferrin saturation (TSAT) \<20%
* Hemoglobin \<14 g/dL for men, \< 13 g/dL for women.
* Stable on heart failure therapy for ≥2-4 weeks
* Currently prescribed a diuretic at home
* Ambulatory (able to walk \>20 ft with minimal assistance)
* Willing and able to give informed consent

Exclusion Criteria:

* Received IV iron, ESA, or blood transfusion within the last 6-12 months
* Received high-dose oral iron (\>100 mg/day in past 7 days)
* Severe renal impairment (eGFR \<15 mL/min/1.73 m² or on dialysis)
* Patients with known cirrhosis or transaminitis with AST \>141 or ALT \>112 IU/L
* Active bleeding or known bleeding disorder
* Recent cardiac surgery, myocardial infarction, or stroke within past 3 months
* Active infection, defined as any systemic or deep-seated infection (e.g., bacteremia, sepsis, osteomyelitis, or infections requiring IV antibiotics or hospitalization) at the time of screening.
* Active malignancy or undergoing chemotherapy/radiotherapy
* Vitamin B12 or folate deficiency (unless corrected prior to enrollment)
* Chronic liver disease (with LFTs \>3× upper limit of normal)
* Pregnant or breastfeeding women or those not using effective contraception
* Lacks capacity to consent or unable to comply with study procedures

Where this trial is running

Bowling Green, Kentucky

• The Medical Center — Bowling Green, Kentucky, United States (Recruiting)

Study contacts

• Study coordinator: Syed H Mufarrih, MD

Conditions Heart Failure; Heart Failure With Reduced Ejection Fraction; Heart Failure With Preserved Ejection Fraction; Iron Deficiency; Iron-deficiency Anemia; Intravenous iron; Oral iron; Ferric carboxymaltose