Intravenous Iron for Heart Failure

(IRONMETHFpEF Trial)

Overseen By Rajeev Malhotra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must not be taking: IV iron, Erythropoietin

Disqualifiers: Iron overload, GI bleeding, Anemia, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a single dose of intravenous iron, known as Ferric Derisomaltose, can enhance exercise capacity in individuals with a specific type of heart failure, where the heart pumps normally but doesn't fill with blood properly. Researchers will compare the effects of the iron treatment to a placebo, a harmless saltwater solution, to assess any improvements in exercise capacity. The trial seeks participants who have experienced stable heart failure for at least four weeks and have a reduced ability to exercise. As a Phase 4 trial, this research seeks to understand how this already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow iron-containing multivitamins with less than 30 mg of iron per day. You cannot participate if you are currently or planning to take intravenous iron supplements.

What is the safety track record for Ferric Derisomaltose?

Research has shown that ferric derisomaltose, the treatment used in this trial, has been studied for safety in people with heart failure. The IRONMAN study, which focused on patients with heart failure and low iron levels, tested ferric derisomaltose for safety and long-term effects. The study found it to be well-tolerated, meaning most participants did not experience serious side effects. This suggests that ferric derisomaltose is generally safe for human use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Ferric derisomaltose is unique because it delivers iron intravenously, which can be more efficient and faster-acting compared to oral iron supplements commonly used for heart failure patients. This treatment is particularly exciting because it bypasses the digestive system, allowing for direct absorption and potentially quicker replenishment of iron stores. Moreover, it may reduce the gastrointestinal side effects often associated with oral iron, improving patient comfort and adherence. Researchers are hopeful that this could lead to better outcomes for heart failure patients who struggle with iron deficiency.

What evidence suggests that ferric derisomaltose might be an effective treatment for heart failure?

In this trial, participants will receive either ferric derisomaltose or a placebo. Research has shown that ferric derisomaltose, an intravenous iron treatment, can benefit heart failure patients with iron deficiency. One study found that patients receiving this treatment had fewer hospital visits for heart failure and a lower risk of death from heart-related issues compared to those who did not receive it. Another study demonstrated that this iron treatment improved patients' quality of life and was cost-effective. Although the IRONMAN trial did not find it superior to standard care, other evidence suggests it can improve outcomes, particularly for those with heart failure where the heart pumps less effectively. Overall, ferric derisomaltose generally enhances health for heart failure patients with iron deficiency. ^{2 4 6 7 8}

Who Is on the Research Team?

Greg Lewis, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults with heart failure and preserved ejection fraction, stable condition, iron deficiency (specific serum ferritin and TSAT levels), reduced exercise capacity, certain NT-proBNP levels or history of heart issues. Excludes pregnant women not using contraception, recent stroke/heart attack patients, those with severe liver/renal disease, known allergies to the study drug, ongoing iron treatments/blood transfusions.

Inclusion Criteria

My heart failure condition has been stable for at least 4 weeks.

Your blood test shows low iron levels, but not extremely low.

You need to do a special breathing and exercise test and reach a certain level of effort.

Exclusion Criteria

My kidney function is severely impaired.

You are allergic to any part of the medication ferric derisomaltose (Monofer®).

You have a condition that makes it difficult to do exercise testing, like severe leg pain, uncontrolled heart rhythm problems, serious muscle or bone diseases, or very high body weight.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline measurements including CPET, echocardiogram, actigraphy, research biomarkers, and KCCQ

1 week

1 visit (in-person)

Treatment

Participants receive a single dose of ferric derisomaltose or placebo and are monitored for immediate reactions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in exercise capacity and other health metrics

12 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ferric Derisomaltose

Trial Overview

The trial is testing if a single dose of intravenous iron (ferric derisomaltose) can improve exercise ability in people with heart failure who have normal heart pumping function but are low on iron. Exercise capacity will be measured by changes in peak oxygen uptake after 12 weeks compared to before treatment.

How Is the Trial Designed?

Group I: Arm 1 Active Control 1 Intervention

Ferric derisomaltose (Monoferric®) 1000 mg X 1 (for subject \<50 kg, 20 mg/kg X1)

Group II: Arm 2 Placebo Group 1 Intervention

Normal Saline

Ferric Derisomaltose is already approved in United States, European Union for the following indications:

Approved in United States as Monoferric for:

• Iron deficiency anemia in adults with intolerance to oral iron or unsatisfactory response to oral iron or non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Approved in European Union as Monofer for:

• Iron deficiency anemia in adults with intolerance to oral iron or unsatisfactory response to oral iron or non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Pharmacosmos A/S

Industry Sponsor

Trials

45

Recruited

9,700+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a study involving 1137 patients with heart failure and iron deficiency, intravenous ferric derisomaltose was associated with a lower risk of hospital admissions for heart failure and cardiovascular death compared to usual care, suggesting its efficacy in improving long-term outcomes.

Patients receiving ferric derisomaltose experienced fewer serious cardiac adverse events (36%) compared to those receiving usual care (43%), indicating a potential safety benefit in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Kalra, PR., Cleland, JGF., Petrie, MC., et al.[2023]

In a study involving 1132 patients with acute heart failure and iron deficiency, treatment with intravenous ferric carboxymaltose was found to significantly reduce the risk of heart failure hospitalizations compared to placebo, with a rate ratio of 0.74.

Ferric carboxymaltose was safe for patients, showing no significant difference in cardiovascular death rates compared to placebo, indicating that while it helps manage heart failure, it does not affect overall mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Ponikowski, P., Kirwan, BA., Anker, SD., et al.[2021]

Ferric derisomaltose is a newer intravenous iron formulation that allows for the delivery of 1000 mg of iron in a single infusion, significantly reducing the risk of serious hypersensitivity reactions (HSRs).

This formulation rapidly replenishes iron levels in patients, providing a convenient treatment option that minimizes adherence issues and lowers healthcare resource utilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose for the treatment of iron deficiency anemia. Auerbach, M., Henry, D., DeLoughery, TG.[2021]

The IRONMAN trial investigated the efficacy of intravenous ferric derisomaltose in treating heart failure patients with iron deficiency, demonstrating significant improvements in iron levels and heart function.

This study involved a randomized, open-label design, providing robust evidence for the safety and effectiveness of ferric derisomaltose in enhancing the quality of life for patients suffering from both heart failure and iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In HF with iron deficiency, IV ferric derisomaltose was associated with lower rates of HF hospitalization or CV death. Lerman, JB., Newby, LK.[2023]

The CONFIRM-HF study is investigating the efficacy and safety of intravenous ferric carboxymaltose (FCM) in treating iron deficiency in patients with chronic heart failure over a 52-week period, involving 304 patients across 41 centers.

Preliminary results from the FAIR-HF study indicated that FCM improved symptoms and quality of life in chronic heart failure patients, suggesting that FCM could be an effective treatment option for managing iron deficiency in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the CONFIRM-HF study: a double-blind, randomized, placebo-controlled study to assess the effects of intravenous ferric carboxymaltose on functional capacity in patients with chronic heart failure and iron deficiency. Ponikowski, P., van Veldhuisen, DJ., Comin-Colet, J., et al.[2019]

Ferric derisomaltose is an effective intravenous iron treatment that allows for complete iron repletion in a single high-dose infusion, making it a rapid and cost-effective option for patients with iron deficiency.

It has a good safety profile, with rare occurrences of serious reactions like anaphylaxis and lower rates of hypophosphatemia compared to older intravenous iron formulations, indicating its suitability for a wide range of patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of ferric derisomaltose as a treatment for anemia. Kassianides, X., Bodington, R., Bhandari, S.[2021]

Ferric derisomaltose (FDI) is a safe and effective treatment for iron deficiency anemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD), showing a lower rate of cardiovascular adverse events compared to iron sucrose (IS).

Patients receiving a single infusion of FDI experienced a faster hematological response, with significant improvements in hemoglobin and ferritin levels, compared to those receiving multiple doses of IS, regardless of their history of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intravenous Ferric Derisomaltose Compared to Iron Sucrose for Iron Deficiency Anemia in Patients with Chronic Kidney Disease With and Without Heart Failure. Ambrosy, AP., von Haehling, S., Kalra, PR., et al.[2021]

Modern intravenous (IV) iron products like ferric derisomaltose (FDI), ferric carboxymaltose (FCM), and ferumoxytol (FER) have improved safety profiles, allowing for rapid administration of high doses to treat iron deficiency and iron deficiency anemia in large populations.

While immediate infusion reactions can occur, they are usually mild and severe reactions are rare; however, hypophosphatemia is a notable side effect of FCM, and ongoing trials will further assess the cardiovascular safety of these IV iron treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer formulations of intravenous iron: a review of their chemistry and key safety aspects - hypersensitivity, hypophosphatemia, and cardiovascular safety. Blumenstein, I., Shanbhag, S., Langguth, P., et al.[2021]

In a study of 70 patients with systolic heart failure, intravenous ferric-carboxy maltose significantly improved exercise capacity and quality of life measures after 12 weeks compared to standard care.

Despite these improvements, the treatment did not lead to changes in ejection fraction, indicating that while ferric-carboxy maltose helps with symptoms, it may not directly affect heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ferric-carboxy maltose on oxygen kinetics and functional status in heart failure patients with iron deficiency. Dhoot, S., Mittal, S., Singh, SP., et al.[2020]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40582343/

Effects of Ferric Derisomaltose in Heart Failure with Iron ...

The primary composite endpoint of recurrent hospitalisation for HF and cardiovascular (CV) death was lower in those assigned to FDI. Analysis ...

2.

acc.org

acc.org/Latest-in-Cardiology/Clinical-Trials/2022/11/04/14/19/ironman

Effectiveness of Intravenous Iron Treatment Versus ...

The IRONMAN trial showed that iron (ferric derisomaltose) infusion is not superior to usual care among patients with HF and iron deficiency.

3.

thelancet.com

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

Intravenous ferric derisomaltose in patients with heart ...

Data from IRONMAN, showing improvements in outcomes in patients with heart failure and both reduced and mildly reduced ejection fraction ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0002914921004227

Safety and Efficacy of Intravenous Ferric Derisomaltose ...

A single infusion of FDI was safe, well tolerated, and was associated with fewer cardiovascular AEs and a faster hematological response, compared to multiple ...

5.

academic.oup.com

academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.852/7835243

Ferric derisomaltose versus usual care in patients with heart ...

This short-term, within-trial CUA suggests that FDI both improves QALYs and reduces healthcare expenditure versus usual care when administered to patients with ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39938943/

Age-stratified effects of intravenous ferric derisomaltose in ...

Abstract · Background: Intravenous iron therapy with ferric derisomaltose (FDI) has been shown to improve outcomes in patients with heart failure ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9850675/

Ferric derisomaltose therapy and heart failure

IRONMAN was a prospective, randomized, open-label, blinded-endpoint trial of the safety and long-term effects of ferric derisomaltose treatment ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06929806

Study Details | NCT06929806 | Multi-center Trial of Ferric ...

Researchers will compare treatment with ferric derisomaltose to no treatment with ferric derisomaltose. This will be done to see how well ferric derisomaltose ...