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

NCT07053475 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 24-11-18-Mufa-OralvsIV-IronAR2059
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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:

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

Conditions

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

Keywords

Intravenous iron; Oral iron; Ferric carboxymaltose; Ferrous sulfate; Transferrin saturation (TSAT); Functional iron deficiency; 6-minute walk test (6MWT); Kansas City Cardiomyopathy Questionnaire (KCCQ); Quality of life; Randomized controlled trial; Congestive heart failure; HFpEF; HFrEF

Outcome Measures

Primary Outcomes (1)

• Change in 6-Minute Walk Distance

  Change in distance (in meters) walked during the 6-minute walk test from baseline to 12 weeks.

  Baseline and 12 weeks

Secondary Outcomes (7)

• Change in NYHA Functional Class

  Baseline and 12 weeks

• Change in Quality of Life

  Baseline and 12 weeks

• Change in Iron Stores

  Baseline and 12 weeks

• All-Cause Mortality

  Through 12 weeks

• Heart Failure Readmissions

  Through 12 weeks

Study Arms (2)

IV Iron (Ferric Carboxymaltose)

EXPERIMENTAL

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).

Drug: Ferric Carboxymaltose

Oral Iron (Ferrous Sulfate)

ACTIVE COMPARATOR

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

Drug: Ferrous Sulfate

Interventions

Ferric Carboxymaltose DRUG

Intravenous infusion of 1 gram FCM during index hospital stay, followed by a second dose at Week 6 (1,000 mg if \> 70 kg or 500 mg if ≤ 70 kg).

Also known as: FCM, IV Iron

IV Iron (Ferric Carboxymaltose)

Ferrous Sulfate DRUG

Oral administration of one 150 mg capsule every 48 hours for 12 weeks.

Also known as: Ferrex, Oral Iron

Oral Iron (Ferrous Sulfate)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Syed Hamza Mufarrih: lead
• American Regent, Inc.: collaborator

Study Sites (1)

The Medical Center

Bowling Green, Kentucky, 42101, United States

RECRUITING

Related Publications (7)

• von Haehling S, Doehner W, Evertz R, Garfias-Veitl T, Derad C, Diek M, Karakas M, Birkemeyer R, Fillippatos G, Lainscak M, Butler J, Ponikowski P, Bohm M, Friede T, Anker SD. Ferric carboxymaltose and exercise capacity in heart failure with preserved ejection fraction and iron deficiency: the FAIR-HFpEF trial. Eur Heart J. 2024 Oct 5;45(37):3789-3800. doi: 10.1093/eurheartj/ehae479.

  PMID: 39185895 BACKGROUND

• Alcaide-Aldeano A, Garay A, Alcoberro L, Jimenez-Marrero S, Yun S, Tajes M, Garcia-Romero E, Diez-Lopez C, Gonzalez-Costello J, Mateus-Porta G, Cainzos-Achirica M, Enjuanes C, Comin-Colet J, Moliner P. Iron Deficiency: Impact on Functional Capacity and Quality of Life in Heart Failure with Preserved Ejection Fraction. J Clin Med. 2020 Apr 22;9(4):1199. doi: 10.3390/jcm9041199.

  PMID: 32331365 BACKGROUND

• Bekfani T, Pellicori P, Morris D, Ebner N, Valentova M, Sandek A, Doehner W, Cleland JG, Lainscak M, Schulze PC, Anker SD, von Haehling S. Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life. Clin Res Cardiol. 2019 Feb;108(2):203-211. doi: 10.1007/s00392-018-1344-x. Epub 2018 Jul 26.

  PMID: 30051186 BACKGROUND

• Cleland JGF, Pellicori P, Graham FJ, Lane R, Petrie MC, Ahmed F, Squire IB, Ludman A, Japp A, Al-Mohammad A, Clark AL, Szwejkowski B, Critoph C, Chong V, Schiff R, Nageh T, Glover J, McMurray JJV, Thomson EA, Robertson M, Ford I, Kalra PA, Kalra PR; IRONMAN Study Group. Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure. J Am Coll Cardiol. 2024 Oct 29;84(18):1704-1717. doi: 10.1016/j.jacc.2024.08.052.

  PMID: 39443013 BACKGROUND

• Manceau H, Ausseil J, Masson D, Feugeas JP, Sablonniere B, Guieu R, Puy H, Peoc'h K. Neglected Comorbidity of Chronic Heart Failure: Iron Deficiency. Nutrients. 2022 Aug 5;14(15):3214. doi: 10.3390/nu14153214.

  PMID: 35956390 BACKGROUND

• Zhou X, Xu W, Xu Y, Qian Z. Iron Supplementation Improves Cardiovascular Outcomes in Patients with Heart Failure. Am J Med. 2019 Aug;132(8):955-963. doi: 10.1016/j.amjmed.2019.02.018. Epub 2019 Mar 7.

  PMID: 30853478 BACKGROUND

• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.

  PMID: 35363499 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Iron Deficiencies; Anemia, Iron-Deficiency

Interventions

ferric carboxymaltose; Fosfomycin; ferryl iron; ferrous sulfate; Iron

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Central Study Contacts

Syed H Mufarrih, MD

CONTACT

304-598-4218; hamzamufarrih@live.com

Melinda Joyce

CONTACT

(270) 535-6879; JoycMC@MCHealth.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Investigators and participants know group assignment. 6-minute walk test staff, data analysts, and clinical endpoint adjudicators remain blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized, 1:1, parallel-group, open-label PROBE design comparing IV ferric carboxymaltose with oral ferrous sulfate in adults with heart failure and TSAT \< 20 %.

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 8, 2025
• Study Start: April 2, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: July 8, 2025

Record last verified: 2025-06

Locations

US (1)