Iron Deficiency Anemia
Conditions
Keywords
Cardiac surgery, Postoperative anemia, Intravenous iron, Postoperative disability
Brief summary
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
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.
Interventions
DRUGFerric Derisomaltose 100 MG/ML
Postoperative treatment with a single dose IVI (ferric derisomaltose), with a dose of 20mg/kg in approximately 60 minutes.
DRUGSodium chloride
Postoperative treatment with a single dose NaCl 0.9% in approximately 60 minutes.
Sponsors
dr. P. Noordzij
Pharmacosmos A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Investigator and patient will be blinded for treatment allocation. As the IVI solution is brown and the placebo solution is colourless, the infusion bags and lines will be light-protected in order to prevent identification of the investigational product.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disability | 90 days after elective cardiac surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in patient reported outcome measures (PROMs) related to dyspnea | 90 days after elective cardiac surgery | 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. |
| Change in patient reported outcome measures (PROMs) related to health related quality of life (HRQL) | 90 days after elective cardiac surgery | 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. |
| Red blood cell transfusions | +/- 7 days after elective cardiac surgery | Number of red blood cell transfusions during hospital stay |
| Change in reticulocyte hemoglobin content | +/- 7 days after elective cardiac surgery | Change in reticulocyte hemoglobin content from randomization to hospital discharge |
| Change in Hb level | +/- 7 days after elective cardiac surgery | Change in Hb level from randomization to hospital discharge |
| Postoperative complications | +/- 7 days after elective cardiac surgery | Postoperative complications during hospital stay |
| Days alive and out of hospital | 90 days after elective cardiac surgery | Days alive and out of hospital |
Countries
Netherlands
Contacts
CONTACTPeter Noordzij, MD, PhD
CONTACTRosa Smoor, MD
PRINCIPAL_INVESTIGATORPeter Noordzij, MD, PhD
St. Antonius Hospital
Outcome results
None listed