AGE-ANEMIA: Intravenous Iron to Treat Postoperative Anemia in Older Cardiac Surgery Patients

Sponsor

dr. P. Noordzij (Other)

Overall Status

Recruiting

CT.gov ID

NCT04913649

Collaborator

Pharmacosmos A/S (Industry)

310

Enrollment

Locations

Arms

14.3

Anticipated Duration (Months)

155

Patients Per Site

10.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia	Drug: Ferric Derisomaltose 100 MG/ML Drug: Sodium chloride	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

310 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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 (Participant, 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.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 23, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Ferric Derisomaltose 100 MG/ML Postoperative treatment with a single dose IVI (ferric derisomaltose), with a dose of 20mg/kg in approximately 60 minutes. Other Names: Monofer
Placebo Comparator: 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	Drug: Sodium chloride Postoperative treatment with a single dose NaCl 0.9% in approximately 60 minutes. Other Names: Placebo

Arm

Intervention/Treatment

Experimental: 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

Drug: Ferric Derisomaltose 100 MG/ML

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

Other Names:

Monofer

Placebo Comparator: 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

Drug: Sodium chloride

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

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Other Outcome Measures

Functional outcome (exploratory endpoint) [+/- 90 days after elective cardiac surgery]
As part of routine care, patients are offered a cardiac revalidation program supervised by a physical therapist after hospital discharge (POD 90). To assess whether patients can safely start exercising, a functional test is performed (e.g. steep ramp or 6-minute walk test). For this study, the results of these tests will be requested to assess functional capacity after surgery
Change in Hb level at 90 days (exploratory endpoint) [+/- 90 days after elective cardiac surgery]
Laboratory results (i.e. Hb values if available) assessed by the treating cardiologist are requested when patients have visited the hospital during follow-up

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Amphia Hospital	Breda		Netherlands
2	St Antonius Hospital	Nieuwegein		Netherlands

Sponsors and Collaborators

dr. P. Noordzij
Pharmacosmos A/S

Investigators

Principal Investigator: Peter Noordzij, MD, PhD, St. Antonius ziekenhuis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

dr. P. Noordzij, Principal investigator, St. Antonius Hospital

ClinicalTrials.gov Identifier:

NCT04913649

Other Study ID Numbers:

NL77442.100.21

First Posted:

Jun 4, 2021

Last Update Posted:

Sep 29, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by dr. P. Noordzij, Principal investigator, St. Antonius Hospital

Cardiac surgery

Postoperative anemia

Intravenous iron

Postoperative disability

Additional relevant MeSH terms:

Anemia

Anemia, Iron-Deficiency

Study Results

No Results Posted as of Sep 29, 2021