Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients

NCT ID: NCT04913649

Last Updated: 2024-12-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-23
• Study Completion Date: 2025-12-31

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.

Conditions

Iron Deficiency Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intravenous iron (ferric derisomaltose)

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

Group Type: EXPERIMENTAL

Ferric Derisomaltose 100 MG/ML

Intervention Type: DRUG

Postoperative treatment with a single dose IVI (ferric derisomaltose), with a dose of 20mg/kg in approximately 60 minutes.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Sodium chloride

Intervention Type: DRUG

Postoperative treatment with a single dose NaCl 0.9% in approximately 60 minutes.

Interventions

Ferric Derisomaltose 100 MG/ML

Postoperative treatment with a single dose IVI (ferric derisomaltose), with a dose of 20mg/kg in approximately 60 minutes.

Intervention Type: DRUG

Sodium chloride

Postoperative treatment with a single dose NaCl 0.9% in approximately 60 minutes.

Intervention Type: DRUG

Other Intervention Names

Monofer; Placebo

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)

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacosmos A/S

INDUSTRY

Sponsor Role: collaborator

dr. P. Noordzij

OTHER

Sponsor Role: lead

Responsible Party

dr. P. Noordzij

Principal investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peter Noordzij, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Antonius Hospital

Locations

Amphia Hospital

Breda, , Netherlands

Site Status: RECRUITING

St Antonius Hospital

Nieuwegein, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Peter Noordzij, MD, PhD

Role: CONTACT

p.noordzij@antoniusziekenhuis.nl

883203000 ext. + 31 (0)

Rosa Smoor, MD

Role: CONTACT

r.smoor@antoniusziekenhuis.nl

883203000 ext. + 31 (0)

Facility Contacts

Thijs Rettig

Role: primary

Peter Noordzij

Role: primary

Rosa Smoor

Role: backup

References

Smoor RM, Rettig TCD, Vernooij LM, Groenewegen EM, van Dongen HPA, Noordzij PG. The effect of postoperative intravenous iron in anaemic, older cardiac surgery patients on disability-free survival (AGE ANEMIA study): study protocol for a multi-centre, double-blind, randomized, placebo-controlled trial. Trials. 2023 Oct 26;24(1):693. doi: 10.1186/s13063-023-07725-y.

Reference Type: DERIVED

PMID: 37885026 (View on PubMed)

Other Identifiers

NL77442.100.21

Identifier Type: -

Identifier Source: org_study_id