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

Syed Hamza Mufarrih

Status and phase: Enrolling; Phase 4

Conditions: Iron-deficiency Anemia (IDA); Iron Deficiency; Heart Failure With Preserved Ejection Fraction (HFPEF); Heart Failure; Heart Failure With Reduced Ejection Fraction (HFrEF)

Treatments: Drug: Ferric Carboxymaltose; Drug: Ferrous Sulfate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07053475

24-11-18-Mufa-OralvsIV-Iron

AR2059 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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250 participants in 2 patient groups

IV Iron (Ferric Carboxymaltose)

Experimental group

Description:

Patients randomized to receive intravenous ferric carboxymaltose. Dosing includes a 1-gram IV infusion during the index hospital stay, followed by a second infusion at Week 6 (1,000 mg if \> 70 kg or 500 mg if ≤ 70 kg).

Treatment:

Drug: Ferric Carboxymaltose

Oral Iron (Ferrous Sulfate)

Active Comparator group

Description:

Patients randomized to receive one capsule of oral ferrous sulfate (Ferrex 150 mg) every 48 hours for 12 weeks.

Treatment:

Drug: Ferrous Sulfate