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

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to determine if the correction of functional iron deficiency by administering a single dose of intravenous iron (ferric derimaltose or Monoferric®) in participants with heart failure with preserved ejection fraction (HFpEF) will improve exercise capacity as measured by the change in peak oxygen uptake (peak VO2) from baseline to 12 weeks.

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 data supports the effectiveness of the drug Ferric Derisomaltose for heart failure?

Research shows that intravenous ferric derisomaltose can lower the rates of hospitalizations and deaths related to heart failure in patients with iron deficiency. Similar treatments, like ferric carboxymaltose, have also been shown to improve quality of life and exercise capacity in heart failure patients. ^{1 2 3 4 5}

Is intravenous ferric derisomaltose safe for humans?

Ferric derisomaltose is generally safe for humans, with a low rate of serious allergic reactions and fewer heart-related side effects compared to other iron treatments. Severe allergic reactions are very rare, and low phosphate levels in the blood are less common with this treatment than with others. ^{1 2 6 7 8}

How is the drug ferric derisomaltose different from other treatments for heart failure?

Ferric derisomaltose is unique because it can be given as a single high-dose intravenous infusion, which quickly replenishes iron levels with a low risk of serious allergic reactions. This makes it more convenient and potentially safer compared to other iron treatments that may require multiple doses or have higher risks of side effects. ^{1 2 4 8 9}

Research Team

Greg Lewis, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

I am 18 years or older and can give my consent.

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effect of ferric-carboxy maltose on oxygen kinetics and functional status in heart failure patients with iron deficiency. [2020]

4. England 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. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Newer formulations of intravenous iron: a review of their chemistry and key safety aspects - hypersensitivity, hypophosphatemia, and cardiovascular safety. [2021]

7. United States 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. [2021]

8. England pubmed.ncbi.nlm.nih.gov

An evaluation of ferric derisomaltose as a treatment for anemia. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose for the treatment of iron deficiency anemia. [2021]