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

NCT ID: NCT07053475

Last Updated: 2025-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-02

Study Completion Date

2027-03-31

Brief Summary

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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

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 %.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Investigators and participants know group assignment. 6-minute walk test staff, data analysts, and clinical endpoint adjudicators remain blinded.

Study Groups

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IV Iron (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).

Group Type EXPERIMENTAL

Ferric Carboxymaltose

Intervention Type 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).

Oral Iron (Ferrous Sulfate)

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

Group Type ACTIVE_COMPARATOR

Ferrous Sulfate

Intervention Type DRUG

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

Interventions

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Ferric Carboxymaltose

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).

Intervention Type DRUG

Ferrous Sulfate

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

Intervention Type DRUG

Other Intervention Names

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FCM, IV Iron Ferrex, Oral Iron

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American Regent, Inc.

INDUSTRY

Sponsor Role collaborator

Syed Hamza Mufarrih

OTHER

Sponsor Role lead

Responsible Party

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Syed Hamza Mufarrih

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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The Medical Center

Bowling Green, Kentucky, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Syed H Mufarrih, MD

Role: CONTACT

304-598-4218

Melinda Joyce

Role: CONTACT

(270) 535-6879

Facility Contacts

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Melinda Joyce, PharmD, FAPhA, FACHE

Role: primary

(270) 535-6879

References

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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.

Reference Type BACKGROUND
PMID: 39185895 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32331365 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30051186 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39443013 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35956390 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30853478 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35363499 (View on PubMed)

Other Identifiers

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AR2059

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

24-11-18-Mufa-OralvsIV-Iron

Identifier Type: -

Identifier Source: org_study_id

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