Iron Deficiency Anemia
Conditions
Keywords
pre surgery iron treatment
Brief summary
Patients with IDA and for whom fast replenishment of iron stores is necessary, e.g. if its not appropriated to postpone surgery, will be identified within 28 to 42 days before surgery. Patients will be randomised to receive either Polyglucoferron intravenously (i.v.), Ferric Carboxymaltose i.v. or oral iron substitution with Ferrous sulfate.
Detailed description
Randomised, active-controlled, open-labelled, parallel group, multicentre study to demonstrate superiority of Polyglucoferron i.v. compared to oral iron substitution for the treatment of iron deficient anaemic patients who need fast replenishment of iron stores as judged by the treating physician, e.g. if it is not appropriate to postpone surgery, before elective non-cardiac surgery and superiority of Polyglucoferron i.v. vs Ferric Carboxymaltose in short term safety monitoring.
Interventions
DRUGPolyglucoferron
intravenous administration
DRUGFerric carboxymaltose
intravenous administration
DRUGFerrous Sulfate
oral administration
Sponsors
University Hospital Frankfurt, Department of Anaesthesiology
IRON4U
University Hospital Frankfurt Institute for Biostatistics & Mathematical Modelling
Dr. Frank Behrens
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
2:2:1 distribution Polyglucoferron, Ferric Carboxymaltose i.v., or oral iron substitution with Ferrous sulfate. After safety assessment of first 35 patients treated with Polyglucoferron or Ferric Carboxymaltose i.v. respectively, Ferric Carboxymaltose arm will be closed.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female; aged ≥ 18 years * Planned to undergo non-cardiac surgery (e.g., orthopaedic, vascular, visceral surgery) within 28 to 42 days, which requires a fast replenishment of the patients' iron stores (e.g.if it is not appropriate to postpone surgery) as judged by the treating physician * Iron deficiency defined as s-ferritin \<100 ng/mL and s-transferrin saturation \<20% * Relevant anaemia defined as haemoglobin of \<12 g/dL for female and \<13 g/dL for men * Written informed consent; willing and able to comply with the protocol
Exclusion criteria
* Pregnancy in female patients or breastfeeding women * Female patients not willing to use a safe method of contraception (PEARL index \<1) for the full study period * Severe anaemia with Hb \< 8 g/dL * Any ingoing bleeding as judged by the treating physician * Patients receiving blood transfusion 24 weeks prior screening * Severe physical inability, e.g., American Society of Anesthesiologists (ASA) physical status IV or V * Haematuria and proteinuria of unknown or known origin * Non-iron deficiency anaemia, e.g., known Vitamin B12 or folate deficiency, haemoglobinopathy, or unexplained anaemia * Anticipated medical need for erythropoiesis-stimulating agents during the study period * Patients with any contraindication to the investigational products, e.g., 1. known sensitivity to iron or an ingredient of the investigational products 2. History of systemic allergic reactions 3. Haemachromatosis, thalassemia or TSAT \>50% as indicator of iron overload 4. Acute or chronic intoxication 5. Infection (patient on non-prophylactic antibiotics) 6. Chronic liver disease and/or screening Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) above three times the upper limit of the normal range * Chronic kidney disease, defined as Glomerular Filtration Rate (GFR) \<30 mL/min * Serum Creatinine \> 150 μmol/L * Active uncontrolled immune-mediated diseases such as rheumatoid arthritis or inflammatory bowel disease * Primary haematologic disease * Drug or alcohol abuse according to WHO definition * Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study * Current or previous participation in another clinical trial during the last 90 days before screening *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normalisation or Increase of hemaglobin(Hb)-level | baseline (BL) to day before surgery (visit 4) | Proportion of patients achieving normalized Hb-levels (according to World Health Organization (WHO) definition) or an increase of at least 1.5 g/dl Hb at day before surgery (visit 4) compared to baseline (BL) in the Polyglucoferron treatment arm compared to oral iron substitution with Ferrous sulfate |
| Detection of urine iron | approx. 8 hours | Detection of urine iron in the first urine after the end of i.v. administration, defined as short term safety surrogate marker after administration of the i.v. treatments |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Units of allogenic red blood cell transfusion | baseline to visit 5 approx. 70 day | Proportion of units of allogenic red blood cell transfusion from BL until visit 5 |
| Hb values | baseline to visit 4 approx. 35 day | Mean change in Hb at visit 4 compared to BL |
| Transferrin Saturation (TSAT) values | baseline to visit 5 approx. 70 day | Mean change in TSAT at visit 5 compared to BL |
| iron values | baseline to visit 4 approx. 35 day | Mean change in serum iron at visit 4 compared to BL |
| ferritin values | baseline to visit 5 approx. 70 day | Mean change in serum ferritin at visit 5 compared to BL |
| transferrin values | baseline to visit 4 approx. 35 day | Mean change in serum ferritin at visit 4 compared to BL |
| Seriousness of adverse events (AE)/serious adverse events (SAE) | baseline to 28 days after surgery, approx. 56 days | Overall tolerability by seriousness of AEs/SAEs until 28 days after surgery |
| Relationship of adverse events (AE)/serious adverse events (SAE) | baseline to 28 days after surgery, approx. 56 days | Overall tolerability by relationship of AEs/SAEs until 28 days after surgery |
| Severity of adverse events (AE)/serious adverse events (SAE) | baseline to 28 days after surgery, approx. 56 days | Overall tolerability by severity of AEs/SAEs until 28 days after surgery |
| Changes in Laboratory parameters | throughout study conduction, max 77 days | Changes White blood count on each visit |
| incidence of adverse events (AE)/serious adverse events (SAE) | baseline to 28 days after surgery, approx. 56 days | Tolerability by incidence of AEs/SAEs until 28 days after surgery |
| Changes in blood pressure | throughout study conduction, max 77 days | Changes in blood pressure on each visit |
| Changes in heart rate | throughout study conduction, max 77 days | Changes in heart rate on each visit |
| Changes in physical exam | throughout study conduction, max 77 days | Changes in physical exam on each visit |
| adverse events related to administration | at baseline | AEs related to injection/infusion site reactions (i.v. group only) |
| hypersensitivity reactions | at baseline | documentation of anaphylatic or anaphylactoid reactions (i.v. group only) |
| Mortality | within 28 days after surgery, approx. 56 days | All-cause mortality within 28 days after surgery |
| Quality of Life (SF36) | base line to visit 4 approx 35 days | Assessment of Quality of Life by SF36 questionnaire at visits 4 compared to BL |
| Duration of hospital stay | 28 days | Duration of hospital stay (days) until 28 days after surgery |
| Number of patients with normalized Hb-values | baseline to visit 4 approx 35 days | Number of patients with normalized Hb-values after iron substitution (n, %) at visits 4 and 5 |
| Analysis of total iron levels | approx 4 hours | Analysis of total iron levels in plasma at BL after end of iron administration (for the i.v. groups (safety analysis group) only) |
| Changes in vital signs | throughout study conduction, max 77 days | Changes in vital signs on each visit |
| number of adverse events (AE)/serious adverse events (SAE) | baseline to 28 days after surgery, approx. 56 days | Tolerability measured by overall number of AEs/SAEs until 28 days after surgery |
Countries
Germany
Outcome results
None listed