Clinical trial NCT04608539: A Clinical Trial Assessing the Efficacy of Intravenous Iron for the Treatment of Anemia Following Cardiac Surgery
Official title: The Postoperative Iron in Cardiac Surgery (PICS-) Trial: A Randomised Clinical Trial Comparing the Efficacy of Single-, High-dose Intravenous Iron and Oral Iron for the Treatment of Anaemia Following Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anemia Postoperative
Keywords: Anemia
Iron deficiency
Transfusion
Postoperative period
Rehabilitation
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: University of Aarhus
name: Pharmacosmos A/S
First posted: 2020-10-29
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: The proportion of participants who are neither anemic nor have received allogeneic red blood cells since randomisation
timeFrame: 4-week follow-up
Secondary outcomes:
measure: Mean change in hemoglobin level
timeFrame: From baseline to 4-week follow-up
measure: Proportion of participants with a haemoglobin increase ≥ 1.3 mmol/l (≥ 2 g/dL)
timeFrame: From baseline to 4-week follow-up
measure: Mean haemoglobin level
timeFrame: 4-week follow-up
measure: Mean reticulocyte count
timeFrame: 4-week follow-up
measure: Mean plasma iron
timeFrame: 4-week follow-up
measure: Mean plasma ferritin
timeFrame: 4-week follow-up
measure: Mean transferrin saturation
timeFrame: 4-week follow-up
measure: Mean change in haemoglobin level
timeFrame: From the day before surgery to 4-week follow-up
measure: Mean change in reticulocyte count
timeFrame: From the day before surgery to 4-week follow-up
measure: Mean change in plasma iron
timeFrame: From the day before surgery to 4-week follow-up
measure: Mean change in plasma ferritin
timeFrame: From the day before surgery to 4-week follow-up
measure: Mean change in transferrin saturation
timeFrame: From the day before surgery to 4-week follow-up
measure: Proportion of participants transfused with allogeneic red blood cells
timeFrame: From the time of randomisation to 4-week follow-up
measure: Six-minute walk distance
timeFrame: 4-week follow-up
measure: Health-related quality of life
timeFrame: 4-week follow-up
measure: Fatique
timeFrame: 4-week follow-up
measure: New York Heart Association (NYHA) functional class
timeFrame: 4-week follow-up
Other outcomes:
measure: Gastrointestinal symptoms
timeFrame: 4-week follow-up
measure: Treatment adherence to oral iron therapy
timeFrame: 4-week follow-up
measure: Cost-effectiveness analysis
timeFrame: 4-week follow-up
measure: Quality of Recovery Score (QoR9-questionnaire)
timeFrame: 4-week follow-up
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Michael Kremke, MD
role: PRINCIPAL_INVESTIGATOR
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