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

Launched by SYED HAMZA MUFARRIH · Jun 26, 2025

Keywords

ClinConnect Summary

This clinical trial, called IRONICA, is studying the best way to treat low iron levels in adults who have heart failure, a condition where the heart doesn’t pump blood as well as it should. The study compares two types of iron treatments: one given through a vein (IV iron) and one taken as pills by mouth (oral iron). Researchers want to find out which treatment helps people walk farther in a 6-minute walk test, improves their symptoms and quality of life, and is safer with fewer side effects or hospital visits.

Adults with heart failure who have low iron levels and certain heart function measurements may be eligible to join. Participants will be randomly assigned to get either a one-time IV iron infusion (with a possible second dose at 12 weeks) or take iron pills twice daily for 24 weeks. They will have clinic visits to check their progress, including a walking test, simple surveys about symptoms and well-being, and blood tests to measure iron levels. This study aims to help doctors decide the safest and most effective iron treatment for people with heart failure.

Gender

ALL

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