Iron Supplementation for Heart Failure

(IRONICA Trial)

Overseen By Melinda Joyce

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Syed Hamza Mufarrih

Must be taking: Diuretics

Must not be taking: IV iron, ESA

Disqualifiers: Severe renal impairment, Active infection, Recent cardiac events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: 24 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which iron treatment is more effective for adults with congestive heart failure and low iron levels: iron administered intravenously (ferric carboxymaltose) or iron pills (ferrous sulfate). It will compare the effects of these treatments on walking distance, symptoms, and quality of life. Researchers will also examine the safety and side effects of both methods. Participants must have heart failure with specific heart function issues (either HFrEF or HFpEF) and low iron levels (TSAT below 20%) to join. As a Phase 4 trial, this research seeks to understand how the already FDA-approved treatment benefits more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be stable on heart failure therapy for at least 2-4 weeks and currently prescribed a diuretic at home.

What is the safety track record for these treatments?

Previous studies have shown that ferric carboxymaltose, administered through an IV, is generally safe for people with heart failure. Research indicates it does not significantly increase the risk of heart-related deaths or hospital stays compared to standard treatments. Some patients may experience mild side effects, such as headaches or nausea, but serious side effects are rare.

For oral iron, like ferrous sulfate, studies have also shown it to be safe for heart failure patients. It is often well-tolerated, though some people might experience minor digestive issues, such as an upset stomach or constipation. These side effects are usually manageable.

Both treatments have undergone extensive study, and evidence suggests they are safe for people with heart failure who have low iron levels. Participants considering joining this trial can feel reassured by the existing safety data. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for heart failure because they explore different ways to boost iron levels in the body, which is crucial for heart health. Ferric Carboxymaltose is unique because it is delivered intravenously, allowing for a fast and targeted approach, especially beneficial during hospitalization. This delivery method can provide a significant iron boost in a short period, potentially improving symptoms quickly. On the other hand, Ferrous Sulfate is taken orally, offering a more traditional, sustained method of iron supplementation over time. By comparing these two methods, researchers aim to determine which is more effective in managing heart failure symptoms linked to iron deficiency.

What evidence suggests that this trial's treatments could be effective for heart failure?

Research has shown that both IV (intravenous) iron and oral iron can benefit people with heart failure who have low iron levels. In this trial, participants will receive either IV iron, specifically ferric carboxymaltose, or oral iron, such as ferrous sulfate, through randomization. Studies have found that IV iron can reduce hospital visits due to heart failure by 25% and enhance exercise capacity, enabling patients to walk longer distances and feel better overall. Oral iron also improves functional capacity and heart performance, as evidenced by better walking test results and heart health measurements. Both treatments appear safe, but the choice in this trial may depend on the urgency of results and how they integrate into a person's daily routine. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with congestive heart failure and low iron levels (TSAT below 20%) are eligible for this trial. They must have either reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). People who don't meet the specific heart function criteria, or have conditions that could interfere with the study, cannot participate.

Inclusion Criteria

BMI ≥18.0 kg/m²

Hemoglobin levels: >9 g/dL and <14 g/dL for men, >9 g/dL and <13 g/dL for women

Documented elevated NT-proBNP based on BMI and rhythm criteria

Exclusion Criteria

Vitamin B12 or folate deficiency (unless corrected prior to enrollment)

Pregnant or breastfeeding women or those not using effective contraception

My liver tests are more than three times the normal limit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a one-time IV iron infusion with a possible repeat at 12 weeks or take oral iron pills twice each day for 24 weeks

24 weeks

Clinic visits at baseline, 6 weeks, and 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of walking distance, symptoms, quality of life, and iron levels

12 weeks

Follow-up visits at 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ferric Carboxymaltose
• Ferrous Sulfate

Trial Overview The IRONICA trial is testing whether IV ferric carboxymaltose or oral ferrous sulfate is more effective in treating iron deficiency in heart failure patients. It measures improvements in walking distance, symptoms, quality of life, safety, side effects, and hospital readmissions/mortality over a 24-week period.

How Is the Trial Designed?

Group I: IV Iron (Ferric Carboxymaltose) Experimental Treatment 1 Intervention

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 II: Oral Iron (Ferrous Sulfate) Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Syed Hamza Mufarrih

Lead Sponsor

American Regent, Inc.

Industry Sponsor

Trials

62

Recruited

19,300+

Paul Diolosa

American Regent, Inc.

Chief Executive Officer since 2021

BS in Mechanical Engineering from Virginia Polytechnic Institute and State University, MBA from New York Dowling College

Emily Huynh

American Regent, Inc.

Chief Medical Officer since 2022

PharmD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10733736/

Efficacy of ferric carboxymaltose in heart failure with iron ... Iron deficiency (ID) is common in heart failure (HF), with a prevalence of 50%–80%. The presence of ID in HF is associated with reduced exercise capacity, ...

2. medrxiv.org medrxiv.org/content/10.1101/2025.09.11.25335472v1.full-text

A Network Meta-Analysis of 15 Randomized Trials Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America. Journal of Cardiac Failure . 2023 Jul;29(7): ...

3. nature.com nature.com/articles/s41591-025-03671-1

Systematic review and meta-analysis of intravenous iron ... Uncertainty remains about the effect of intravenous (i.v.) iron on outcomes for heart failure (HF) with iron deficiency.

4. thelancet.com thelancet.com/journals/lancet/article/piis0140-6736(22)02083-9/fulltext

Intravenous ferric derisomaltose in patients with heart ... The excess in events for patients in the usual care group appeared to be due to heart failure, acute coronary events, and cardiac arrest ( ...

5. journal-of-cardiology.com journal-of-cardiology.com/article/S0914-5087(23)00157-0/fulltext

Clinical outcomes of intravenous iron therapy in patients ... IV iron leads to a significant reduction in heart failure hospitalization by 25 %. •. No significant difference in cardiac or mortality, GI ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2304968

Ferric Carboxymaltose in Heart Failure with Iron Deficiency Primary Outcome ; Cardiovascular death, 124 (8.1), 141 (9.2) ; Hospitalization for heart failure, 351 (22.9), 353 (23.0) ; Events — no. per 100 patient-yr, 16.0 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425000399

Prediction and Longer-Term Outcomes of All-cause and ... For example, the rates of all-cause mortality after a heart failure hospitalization were 31.8 and 36.1 per 100 patient-years for FCM and placebo ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.008100

Randomized Placebo-Controlled Trial of Ferric ... The objective of the HEART-FID trial (Ferric Carboxymaltose in Heart Failure ... outcomes · prognosis · survival. Subjects. Cardiomyopathy ...