A Clinical Trial Assessing the Efficacy of Intravenous Iron for the Treatment of Anemia Following Cardiac Surgery

NCT ID: NCT04608539

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-21
• Study Completion Date: 2023-06-27

Brief Summary

BACKGROUND Anemia and iron deficiency are highly prevalent in cardiac surgery patients. Both conditions may adversely affect postoperative rehabilitation.

At hospital discharge, anemia is almost invariably present due to perioperative blood loss and frequent blood sampling. Two previous analyses demonstrated a prevalence of anemia early after coronary artery bypass grafting (CABG) of 94% and 98%, respectively. Almost half of CABG patients had persistent anemia two months after surgery. Postoperative anemia may result in debilitating symptoms, like dyspnoea, fatigue and poor exercise tolerance, and is associated with an increased likelihood of cardiovascular events and death after cardiac surgery.

Mild to moderate anemia is commonly corrected with oral iron supplements. Oral iron is however poorly absorbed in patients with chronic diseases, and about 40% of patients suffer from debilitating gastrointestinal side-effects. As iron stores are frequently reduced or depleted after cardiac surgery, treatment with oral iron supplements may take several months.

In patients with chronic heart failure (CHF), iron deficiency is associated with reduced exercise capacity, quality of life and survival even in the absence of anemia. Several large randomised trials demonstrated that treatment with intravenous iron improved clinical symptoms, exercise capacity and quality of life of CHF patients.

RATIONALE It is desirable to replenish body iron stores rapidly after cardiac surgery with the aim to effectively correct anemia, optimize exercise tolerance and improve patient wellbeing.

Modern intravenous iron formulations permit fast replenishment of body iron stores and have emerged as potential alternatives to oral iron. These formulations are well-tolerated and have become an established therapeutic option in anemic patients with reduced intestinal iron absorption. Several studies have demonstrated the efficacy of intravenous iron for the treatment of anemia following major non-cardiac surgery.

Data regarding the efficacy of intravenous iron in cardiac surgery, however, are conflicting.

HYPOTHESIS Single-dose intravenous iron therapy with ferric derisomaltose/iron isomaltoside is superior to oral iron supplementation for the correction of anemia following cardiac surgery. Moreover, single-dose intravenous iron therapy with ferric derisomaltose/iron isomaltoside results in a greater postoperative exercise capacity, an improved quality of life and less fatigue.

Conditions

Anemia Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous iron group

Single-dose intravenous infusion of 20 mg/kg body weight ferric derisomaltose/iron isomaltoside 1000 (MonoFer®)

Group Type: EXPERIMENTAL

Ferric Derisomaltose

Intervention Type: DRUG

Single-dose intravenous infusion, 20 mg/kg body weight, postoperative day 1

Oral iron group

Oral therapy with 100 mg oral ferrous sulfate twice daily

Group Type: ACTIVE_COMPARATOR

Ferrous sulfate

Intervention Type: DRUG

Oral therapy, 100 mg twice daily, from postoperative day 4 until 4-week follow-up

normal saline

Intervention Type: DRUG

Single-dose infusion (placebo), postoperative day 1

Interventions

Ferric Derisomaltose

Single-dose intravenous infusion, 20 mg/kg body weight, postoperative day 1

Intervention Type: DRUG

Ferrous sulfate

Oral therapy, 100 mg twice daily, from postoperative day 4 until 4-week follow-up

Intervention Type: DRUG

normal saline

Single-dose infusion (placebo), postoperative day 1

Intervention Type: DRUG

Other Intervention Names

MonoFer, iron isomaltoside 1000; Ferro Duretter; 0.9% natriumchloride

Eligibility Criteria

Inclusion Criteria

• Patients 18 years of age or older undergoing first-time, non-emergent cardiac surgery with cardiopulmonary bypass. Eligible procedures are A: isolated CABG surgery (+/- arrhythmia surgery), B: isolated cardiac valve surgery (+/- arrhythmia surgery), C: a combination of CABG and cardiac valve surgery (+/- arrhythmia surgery)
• Moderate anaemia on the first postoperative day. According to World Health Organization-criteria defined as a haemoglobin concentration of equal to or greater than 5.0 mmol/l (8 g/dl) and less than 6.8 mmol/l (11 g/dl).

Exclusion Criteria

• Known hypersensitivity to any iron formulation
• Multiple drug allergies or history of previous anaphylaxis
• Severe asthma, eczema or another atopic allergy
• Rheumatoid arthritis or systemic lupus erythematosus
• History of iron overload or disturbances in iron utilisation (e.g. haemochromatosis, hemosiderosis)
• History of liver disease (e.g. cirrhosis)
• Severe active infection or inflammation (e.g. endocarditis)
• Porphyria cutanea tarda
• Treatment with intravenous iron within 4 weeks prior to surgery.
• Untreated vitamin B12 or folate deficiency.
• Anticipated inability to perform a six-minute walk test.
• Women of childbearing potential, pregnant and nursing women.
• Anticipated postoperative length of stay in the intensive care unit (ICU) > 48 hours.
• Patients incapable of giving consent personally.
• Significantly increased risk of non-adherence or loss to follow-up.
• Active participation in another interventional trial with potential impact on postoperative anaemia or exercise capacity.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: collaborator

Pharmacosmos A/S

INDUSTRY

Sponsor Role: collaborator

Michael Kremke

OTHER

Sponsor Role: lead

Responsible Party

Michael Kremke

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Kremke, MD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital

Locations

Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

References

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Other Identifiers

PICS-01

Identifier Type: -

Identifier Source: org_study_id