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

Not Applicable

Recruiting

• Conditions: Heart Failure; Heart Failure With Reduced Ejection Fraction (HFrEF); Heart Failure With Preserved Ejection Fraction (HFPEF); Iron Deficiency; Iron-deficiency Anemia (IDA)
• Interventions: Drug: Ferric Carboxymaltose; Drug: Ferrous Sulfate

• Registration Number: NCT07053475
• Lead Sponsor: Syed Hamza Mufarrih

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-04-02
• Status Verified: 2025-06
• Study First Submitted: 2025-06-26
• Study First Submitted QC: 2025-06-26
• Last Update Submitted: 2025-06-26
• Study First Posted: 2025-07-08
• Last Update Posted: 2025-07-08
• Primary Completion: 2026-12-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV Iron (Ferric Carboxymaltose)	Ferric Carboxymaltose	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).
Oral Iron (Ferrous Sulfate)	Ferrous Sulfate	Patients randomized to receive one capsule of oral ferrous sulfate (Ferrex 150 mg) every 48 hours for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change in 6-Minute Walk Distance	Baseline and 12 weeks	Change in distance (in meters) walked during the 6-minute walk test from baseline to 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Change in NYHA Functional Class	Baseline and 12 weeks	Change in New York Heart Association (NYHA) class from baseline to 12 weeks.
Change in Quality of Life	Baseline and 12 weeks	Change in patient-reported quality of life scores as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Change in Iron Stores	Baseline and 12 weeks	Change in iron parameters including serum ferritin, serum iron, and transferrin saturation from baseline to 12 weeks.
All-Cause Mortality	Through 12 weeks	Death from any cause during the 12-week study period.
Heart Failure Readmissions	Through 12 weeks	Number of heart failure-related hospital readmissions within 12 weeks.
Major Adverse Cardiac Events (MACE)	Through 12 weeks	Composite of cardiovascular death, myocardial infarction, or stroke during the 12-week study period.
Adverse Events Related to Study Drug	Through 12 weeks	Frequency of reported adverse effects attributed to either ferric carboxymaltose or oral ferrous sulfate during the study period.

Trial Locations

Locations (1)

The Medical Center; 🇺🇸 Bowling Green, Kentucky, United States