IRONICA: IRON Repletion In Heart Failure - A Comparison of Oral and IV Approaches

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

The goal of this clinical trial is to learn which iron treatment works better for adults with congestive heart failure and low iron levels: intravenous (IV) iron given through a vein or oral (PO) iron taken by mouth. Participants must have heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) and a transferrin-saturation (TSAT) level below 20 percent.

The main questions the study will answer are:

1. Does IV iron raise walking distance on a 6-minute walk test more than oral iron after 24 weeks?
2. Does IV iron improve symptoms and quality of life more than oral iron?
3. How do the two treatments compare for safety, side effects, and hospital readmissions/ mortality?

Researchers will compare IV ferric carboxymaltose with oral ferrous sulfate to see which option helps people feel and function better.

What participants will do

• Be randomly assigned by (like flipping a coin) to IV iron or oral iron.

• Receive either a one-time IV iron infusion (with possible repeat at 12 weeks) or take iron pills twice each day for 24 weeks.

• Visit the infusion clinic at 6 weeks for second dose of IV iron if needed.

• Visit the clinic at 12 weeks for a follow-up to gather follow-up data including

  1. A 6-minute walk test
  2. Brief symptom and quality-of-life surveys
  3. Blood tests to measure serum iron, ferritin, and transferrin saturation

This study will help doctors decide whether IV or oral iron is the safer, more effective way to treat iron deficiency in people with heart failure in our local community.

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