Clinical trial NCT04913649: Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients
Official title: Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients: a Randomized Controlled Trial'
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Iron Deficiency Anemia
Keywords: Cardiac surgery
Postoperative anemia
Intravenous iron
Postoperative disability
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: Pharmacosmos A/S
First posted: 2021-06-04
Enrollment: 310
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Disability
timeFrame: 90 days after elective cardiac surgery
Secondary outcomes:
measure: Change in patient reported outcome measures (PROMs) related to dyspnea
timeFrame: 90 days after elective cardiac surgery
measure: Change in patient reported outcome measures (PROMs) related to health related quality of life (HRQL)
timeFrame: 90 days after elective cardiac surgery
measure: Red blood cell transfusions
timeFrame: +/- 7 days after elective cardiac surgery
measure: Change in reticulocyte hemoglobin content
timeFrame: +/- 7 days after elective cardiac surgery
measure: Change in Hb level
timeFrame: +/- 7 days after elective cardiac surgery
measure: Postoperative complications
timeFrame: +/- 7 days after elective cardiac surgery
measure: Days alive and out of hospital
timeFrame: 90 days after elective cardiac surgery
Other outcomes:
measure: Functional outcome (exploratory endpoint)
timeFrame: +/- 90 days after elective cardiac surgery
measure: Change in Hb level at 90 days (exploratory endpoint)
timeFrame: +/- 90 days after elective cardiac surgery
Locations:
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Nieuwegein
country: Netherlands
facility: St Antonius Hospital
Study officials:
affiliation: St. Antonius Hospital
name: Peter Noordzij, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: