Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients

Study Overview
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Brief Summary
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Postoperative anemia is common in cardiac surgery with cardiopulmonary bypass. Iron deficiency delays the recovery from postoperative anemia and may negatively affect the postoperative trajectory of cardiac surgery patients. The objective of the study is to determine the effect of treatment of postoperative iron deficiency anemia with intravenous iron on disability 90 days after surgery. This will be evaluated in a randomized placebo-controlled double blind two-center trial in which 310 elective cardiac surgery patients will be included.

Detailed Description
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Rationale: Postoperative anemia is common in cardiac surgery with cardiopulmonary bypass. Iron deficiency delays the recovery from postoperative anemia and may negatively affect the postoperative trajectory of cardiac surgery patients. Objective: To determine the effect of treatment of postoperative iron deficiency anemia (IDA) with intravenous iron (IVI) on disability 90 days after surgery. Study design: Randomized placebo-controlled double blind two-center trial Study population: 310 elderly patients (≥70 years) with moderate postoperative IDA on postoperative day (POD) 1 (hemoglobin (Hb) 85 - 110 g/L, ferritin concentration < 100 µg/L or iron saturation <20%) after uncomplicated elective cardiac surgery (aortic valve repair (AVR) and coronary artery bypass graft (CABG) surgery). Intervention: Postoperative treatment with a single dose IVI (ferric derisomaltose, Monofer®, N = 155) compared to postoperative treatment with sodium chloride (NaCL) 0.9% (placebo, N = 155). Main study endpoints: Primary endpoint is disability as measured by the 12- item World Health Organization Disability Assessment score 2.0 (WHODAS-12 at POD 90 after elective cardiac surgery. Secondary endpoints are change in patient reported outcome measures (PROMs) related to dyspnea (assessed with the Rose Dyspnea Score (RDS)) and to health-related quality of life (HRQL) (assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire) at POD 90, the number of postoperative red blood cell (RBC) transfusions, change in reticulocyte hemoglobin content (pg) from randomization to hospital discharge, Hb levels at discharge, hospital complications and days alive and out of hospital at 90 days. Lastly, the difference in functional outcomes (e.g. steep ramp or 6-minute walk test) and Hb value at POD 90 will be assessed as an exploratory endpoint.

Official Title
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Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients: a Randomized Controlled Trial'

Conditions
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Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Ferric Derisomaltose 100 MG/ML
* Drug: Sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mentally competent with age ≥ 70 years Elective AVR or CABG surgery Expected uncomplicated postoperative trajectory, defined as: No inotropic agents or ventilation at time of final inclusion (POD 1) Expected discharge to general ward at POD 1 Moderate postoperative IDA, defined as: Hb between 85 and 110 g/L and Ferritin <100 µg/L or Iron saturation (TSAT) < 20% Exclusion Criteria: Medical history of iron overload/haemochromatosis Medical history of liver cirrhosis or ALT/AST value in blood serum triple of normal value (female patients: ALT >120, AST >105 U/L. Male patients: ALT>150, AST>135 U/L) Severe renal failure (eGFR<15ml/min/1.73m2) Recent treatment with IVI (<12 weeks prior) Serious or severe allergic reaction to IVI in medical history Severe asthma or eczema in medical history (atopic constitution)

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two center randomized controlled trial. Patients will either receive IVI (Monofer) or placebo. Via a computer generated randomization patients will be randomly assigned (1:1) to either a single dose of intravenous ferric derisomaltose (Monofer) 100 mg/mL solution for infusion (intervention group) or intravenous NaCl 0.9% (placebo group) (randomisation with block size 4). Stratification takes surgical intervention (AVR or CABG) and hospital location into account.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous iron (ferric derisomaltose)<br>The intervention consists of a single dose of ferric derisomaltose (Monofer®) 100 mg/mL solution for infusion (Monofer® is a registered product with a marketing authorization in the Netherlands (RVG number: 103070). Manufacturer: Pharmacosmos A/S, Denmark. Dutch marketing authorization holder: Cablon Medical B.V). The method of administration and dosage of the investigational medication are standard treatment. The ferric derisomaltose dose will calculated for each patient depending on body weight (20mg/kg) and diluted in 250 ml NaCl 0.9%. Treatment takes approximately 60 minutes. Vital signs of the patient will be monitored during administration of the investigational medication and for 30 minutes afterwards | Drug: Ferric Derisomaltose 100 MG/ML<br>* Postoperative treatment with a single dose IVI (ferric derisomaltose), with a dose of 20mg/kg in approximately 60 minutes.<br>* Other names: Monofer;|
| Placebo Comparator: Placebo<br>Single dose of sodium chloride 0.9% (250ml). Treatment takes approximately 60 minutes. Vital signs of the patient will be monitored during administration of the investigational medication and for 30 minutes afterwards | Drug: Sodium chloride<br>* Postoperative treatment with a single dose NaCl 0.9% in approximately 60 minutes.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability | Disability measured by the 12- item World Health Organization Disability Assessment score 2.0 (WHODAS-12). Based on the answers a disability score can be calculated. 0% is no disability and 100% is fully disabled. | 90 days after elective cardiac surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient reported outcome measures (PROMs) related to dyspnea | PROMS related to dyspnea are assessed with the Rose Dyspnea Scale (RDS). Rose Dyspnea Scale scores range from 0 to 4 with higher scores indicating more dyspnea with common activities. | 90 days after elective cardiac surgery | 
| Change in patient reported outcome measures (PROMs) related to health related quality of life (HRQL) | HRQL is assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire. The TOPIC-SF is comprised of 22 items in 7 domains of health and well-being. Scores in the different domains ranges from 0 to 5, higher scores indicating diminished quality of life. | 90 days after elective cardiac surgery | 
| Red blood cell transfusions | Number of red blood cell transfusions during hospital stay | +/- 7 days after elective cardiac surgery | 
| Change in reticulocyte hemoglobin content | Change in reticulocyte hemoglobin content from randomization to hospital discharge | +/- 7 days after elective cardiac surgery | 
| Change in Hb level | Change in Hb level from randomization to hospital discharge | +/- 7 days after elective cardiac surgery | 
| Postoperative complications | Postoperative complications during hospital stay | +/- 7 days after elective cardiac surgery | 
| Days alive and out of hospital | Days alive and out of hospital | 90 days after elective cardiac surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac surgery, Postoperative anemia, Intravenous iron, Postoperative disability