Intravenous Iron for Iron-Deficiency Anemia

(POAM Trial)

Recruiting at 2 trial locations

Overseen By Keyvan Karkouti, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Disqualifiers: Complex surgery, Iron overload, Liver cirrhosis, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Monoferric Injectable Product for treating iron-deficiency anemia?

Research shows that high-dose intravenous iron, like Monoferric, can quickly improve iron levels and reduce symptoms such as fatigue in patients who cannot tolerate or do not respond well to oral iron treatments. ^{1 2 3 4 5}

Is intravenous iron generally safe for humans?

Intravenous iron treatments, including newer formulations like ferric gluconate and iron sucrose, have been shown to have a good overall safety profile, though some potential side effects like skin staining and infusion-related reactions exist. Older formulations like iron dextran had higher risks of severe allergic reactions, but newer options are considered safer and do not require test doses. ^{4 6 7 8 9}

How does intravenous iron differ from other treatments for iron-deficiency anemia?

Intravenous iron, such as iron isomaltoside 1000 (Monofer), is unique because it can be administered in high doses quickly, often in a single infusion, without the need for a test dose, making it suitable for patients who cannot tolerate or do not respond well to oral iron supplements. ^{2 4 8 10 11}

What is the purpose of this trial?

POAM is a multicenter, randomized, controlled, internal pilot trial, using a conventional, parallel group, two-armed design at 3 cardiac surgery centres in Canada. The study is designed to assess the feasibility of a future, definitive RCT investigating whether, in patients with chronic iron-deficiency anemia undergoing cardiac surgery, IV iron therapy in the postoperative period (initiated shortly after surgery, and repeated at 42 days after surgery, if needed) improves clinical outcomes (days alive and out of hospital at 90 days after surgery; DAOH-90) relative to placebo.

Research Team

Justyna Bartoszko, MD

Principal Investigator

University Health Network, Toronto

Jeannie Callum, MD

Principal Investigator

Kingston Health Sciences Centre

Yulia Lin, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for patients with chronic iron-deficiency anemia who are undergoing cardiac surgery. They should be at one of the three participating Canadian centers. The study excludes those who don't meet the specific health criteria set by the researchers, but these aren't detailed here.

Inclusion Criteria

I am scheduled for a non-emergency heart surgery using a heart-lung machine.

I have low iron levels and anemia before surgery.

I am over 18 years old.

Exclusion Criteria

Patients who meet any of the following criteria are not eligible for the study:

Established contraindications to IV iron: hypersensitivity to the iron product, history of >2 food and/or drug allergic reactions (excluding drug intolerance), non-iron deficiency anemias such as myelodysplastic syndrome, history of iron overload or disturbances in use of iron such as hemochromatosis or hemosiderosis, decompensated liver cirrhosis (MELD ≥ 19) or active hepatitis, active infection, preoperative unstable hemodynamics defined as the requirement for vasopressors or inotropes, or active bleeding (as noted in the clinical record and/or defined as a requirement for red blood cell transfusion for ongoing clinical bleeding), refusal of blood products for religious or other reasons, known pregnancy, already enrolled in this trial, enrolment in another interventional trial which may impact anemia or transfusion management (for example, a trial of hemostatic therapies, such as tranexamic acid), receipt of intravenous iron at any point in the 6 weeks prior to randomization

I have undergone or need a complex heart-related surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV iron therapy or placebo shortly after cardiac surgery, with a possible repeat at 42 days post-surgery

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness, with primary outcomes measured at 90 days post-surgery

12 weeks

1 visit (in-person), additional follow-up as needed

Treatment Details

Interventions

• Monoferric Injectable Product

Trial Overview The POAM trial is testing if giving IV iron therapy after cardiac surgery can help patients recover better compared to a saltwater placebo. It's done in two groups: one gets iron and the other gets placebo, chosen randomly.

Participant Groups

Group I: Intervention Group Experimental Treatment 1 Intervention

Patients randomized to the IV iron group will receive 1000 mg ferric derisomaltose (Monoferric) diluted in 100 mL of 0.9 % sodium chloride solution, via intravenous infusion over 1 hour using an opaque IV bag and tubing for blinding.

Group II: Control group Placebo Group 1 Intervention

Patients randomized to the placebo group will receive 100 mL of 0.9 % sodium chloride solution via intravenous infusion using an opaque IV bag and tubing for blinding.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Heart and Stroke Foundation of Canada

Collaborator

Trials

131

Recruited

72,600+

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Kingston Health Sciences Centre

Collaborator

Trials

32

Recruited

34,400+

Findings from Research

Iron deficiency is the leading cause of anemia globally, and iron supplementation effectively increases transferrin saturation and ferritin levels, which helps raise hemoglobin and reduce anemia symptoms.

For patients who cannot absorb iron orally or have significant deficiencies, intravenous iron is necessary, and this paper reviews the available intravenous iron preparations, highlighting their benefits and risks associated with administering high doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFETY AND EFFICACY OF INTRAVENOUS ADMINISTRATION OF IRON PREPARATIONS. Grzywacz, A., Lubas, A., Fiedor, P., et al.[2018]

High-dose intravenous ferric derisomaltose (Monofer®) infusions of 500 and 1000 mg effectively corrected iron deficiency and iron deficiency anemia in elderly patients, leading to rapid improvements in laboratory parameters and symptoms like fatigue.

Intravenous iron administration is a viable treatment option for patients who cannot tolerate oral iron or have poor absorption, potentially reducing morbidity and mortality associated with untreated iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients. Khiatani, D., Tay, HS., Cushway, TR.[2022]

Intravenous iron III-hydroxide saccharate was found to be an effective treatment for adult patients with iron deficiency anemia who did not respond well to oral iron therapy, with a significant increase in hemoglobin levels observed post-treatment.

Out of 25 patients studied, 68% achieved correction of anemia, and none required blood transfusions, highlighting the safety and efficacy of this treatment option, especially for those with severe anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficacy of intravenous iron III-hydroxide saccharate for treating adult patients with iron deficiency anemia]. Cançado, RD., Brasil, SA., Noronha, TG., et al.[2019]

In a study involving 143 non-hemodialysis adult outpatients, both intravenous iron dextran and iron sucrose had similar rates of immediate severe drug reactions, indicating comparable safety in that regard.

However, iron sucrose was associated with a significantly higher risk of delayed infusion reactions compared to iron dextran, suggesting that while both treatments are generally safe, iron dextran may be preferable for minimizing delayed side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study. Louzada, ML., Hsia, CC., Al-Ani, F., et al.[2020]

In a systematic review of five studies involving 694 patients with iron deficiency anemia, there was no significant difference in hemoglobin response between intravenous (IV) and oral (PO) iron treatments.

However, IV iron led to a greater initial increase in serum ferritin levels and a lower risk of withdrawal due to adverse events compared to PO iron, suggesting it may be a safer option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron Replacement in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Abhyankar, A., Moss, AC.[2018]

Intravenous iron replacement is recommended for patients with severe iron deficiency, particularly when oral iron is ineffective or not tolerated, and in cases of inflammation that hinder iron absorption.

Current intravenous iron formulations have a strong safety profile, but potential side effects like skin staining, infusion reactions, and low phosphate levels should be monitored to ensure proper patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous iron: an update. Lucas, S., Garg, M.[2023]

Intravenous iron therapy significantly increases hemoglobin levels and reduces the need for blood transfusions, based on a meta-analysis of 72 trials involving 10,605 patients.

However, while effective, intravenous iron is associated with a higher risk of infection compared to oral or no iron supplementation, indicating a need for careful consideration in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. Litton, E., Xiao, J., Ho, KM.[2022]

Oral iron supplementation is effective and cost-efficient for treating iron deficiency anemia (IDA), but it often causes gastrointestinal side effects and requires a long treatment duration.

New intravenous iron preparations, developed in the last five years, offer improved safety profiles and faster iron replenishment, allowing for higher doses without the risk of anaphylactic reactions associated with older formulations like iron dextran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous iron therapy: how far have we come? Cançado, RD., Muñoz, M.[2021]

In a study involving 72 children, administering intravenous iron sucrose over 90 minutes resulted in only a few minor adverse events, indicating it is a safe method for treating anemia due to chronic renal impairment.

A faster infusion method of 2 mg/kg over 3 minutes was also safe, with only minor adverse events reported in 20 children, suggesting that both methods can be used effectively without life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low incidence of adverse events following 90-minute and 3-minute infusions of intravenous iron sucrose in children on erythropoietin. Anbu, AT., Kemp, T., O'donnell, K., et al.[2019]

Iron isomaltoside 1000 (Monofer) is a novel intravenous iron formulation that has a very low immunogenic potential and allows for high single-dose administration, making it suitable for rapid iron repletion in patients with iron deficiency anemia.

Compared to other intravenous iron preparations, Monofer has significant advantages in terms of safety and convenience, enabling doses over 1000 mg to be given in a single infusion without the need for a test dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Jahn, MR., Andreasen, HB., Fütterer, S., et al.[2022]

In a 12-month trial involving 39 European subjects with inflammatory bowel disease, iron isomaltoside 1000 effectively maintained hemoglobin levels above 12.0 g/dl in 74% of participants, demonstrating its efficacy in managing iron deficiency anemia.

The treatment was well-tolerated, with only minor hypersensitivity reactions reported, indicating a favorable safety profile for repeated high-dose intravenous iron administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease. Reinisch, W., Altorjay, I., Zsigmond, F., et al.[2022]

References

1. Poland pubmed.ncbi.nlm.nih.gov

SAFETY AND EFFICACY OF INTRAVENOUS ADMINISTRATION OF IRON PREPARATIONS. [2018]

2. Malaysia pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients. [2022]

3. Brazil pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficacy of intravenous iron III-hydroxide saccharate for treating adult patients with iron deficiency anemia]. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study. [2020]

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

Iron Replacement in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. [2018]

6. Australia pubmed.ncbi.nlm.nih.gov

Intravenous iron: an update. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. [2022]

8. Brazil pubmed.ncbi.nlm.nih.gov

Intravenous iron therapy: how far have we come? [2021]

9. Norway pubmed.ncbi.nlm.nih.gov

Low incidence of adverse events following 90-minute and 3-minute infusions of intravenous iron sucrose in children on erythropoietin. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. [2022]

11. England pubmed.ncbi.nlm.nih.gov

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease. [2022]