Polyglucoferron Compared to i.v. Ferric Carboxymaltose and Oral Iron Substitution in Preoperative Treatment of Iron Deficiency Anaemia in Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomised, Open Lable, Active Controlled Clinical Trial to Demonstrate Safety and Efficacy of an i.v. Administration of Polyglucoferron Compared to i.v. Ferric Carboxymaltose and Oral Iron Substitution in Preoperative Treatment of Iron Deficiency Anaemia in Patients With Elective Non-cardiac Surgery (IDA I)

Conditions
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Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Polyglucoferron
* Drug: Ferric carboxymaltose
* Drug: Ferrous Sulfate


Participation Criteria
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Eligibility Criteria
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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., known sensitivity to iron or an ingredient of the investigational products History of systemic allergic reactions Haemachromatosis, thalassemia or TSAT >50% as indicator of iron overload Acute or chronic intoxication Infection (patient on non-prophylactic antibiotics) 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 Exclusion criteria related to Ferrous sulfate according to summary of product characteristics (SmPC) hypersensitivity to any ingredient in the formulation concomitant parenteral iron haemochromatosis, and other iron overload syndromes Exclusion criteria related to Ferric Carboxymaltose: according to SmPC hypersensitivity to the active substance, to Ferinject or any of its excipients known serious hypersensitivity to other parenteral iron products anaemia not attributed to iron deficiency evidence of iron overload or disturbances in the utilisation of iron Exclusion criteria related to Polyglucoferron f) hypersensitivity to any ingredient in the formulation known serious hypersensitivity to other parenteral iron products anaemia not attributed to iron deficiency evidence of iron overload or disturbances in the utilisation of iron

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polyglucoferron<br>once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg | Drug: Polyglucoferron<br>* intravenous administration<br>* Other names: Feramyl;|
| Active Comparator: Ferric Carboxymaltose<br>Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg) | Drug: Ferric carboxymaltose<br>* intravenous administration<br>* Other names: Ferinject;|
| Active Comparator: Ferrous sulfate<br>capsules, orally, dosing 50 mg - 200 mg (50 mg: 1 capsule in total, 200 mg: 4 capsules in total, taken as 2 capsules twice daily), duration of treatment 28 days | Drug: Ferrous Sulfate<br>* oral administration<br>* Other names: Ferro sanol duodenal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalisation or Increase of hemaglobin(Hb)-level | 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 | baseline (BL) to day before surgery (visit 4) | 
| Detection of urine iron | 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 | approx. 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Units of allogenic red blood cell transfusion | Proportion of units of allogenic red blood cell transfusion from BL until visit 5 | baseline to visit 5 approx. 70 day | 
| Hb values | Mean change in Hb at visit 4 compared to BL | baseline to visit 4 approx. 35 day | 
| Hb values | Mean change in Hb at visit 5 compared to BL | baseline to visit 5 approx. 70 day | 
| Transferrin Saturation (TSAT) values | Mean change in TSAT at visit 5 compared to BL | baseline to visit 5 approx. 70 day | 
| Transferrin Saturation (TSAT) values | Mean change in TSAT at visit 4 compared to BL | baseline to visit 4 approx. 35 day | 
| iron values | Mean change in serum iron at visit 4 compared to BL | baseline to visit 4 approx. 35 day | 
| iron values | Mean change in serum iron at visit 5 compared to BL | baseline to visit 5 approx. 70 day | 
| ferritin values | Mean change in serum ferritin at visit 5 compared to BL | baseline to visit 5 approx. 70 day | 
| ferritin values | Mean change in serum ferritin at visit 4 compared to BL | baseline to visit 4 approx. 35 day | 
| transferrin values | Mean change in serum ferritin at visit 4 compared to BL | baseline to visit 4 approx. 35 day | 
| transferrin values | Mean change in serum ferritin at visit 5 compared to BL | baseline to visit 5 approx. 70 day | 
| number of adverse events (AE)/serious adverse events (SAE) | Tolerability measured by overall number of AEs/SAEs until 28 days after surgery | baseline to 28 days after surgery, approx. 56 days | 
| incidence of adverse events (AE)/serious adverse events (SAE) | Tolerability by incidence of AEs/SAEs until 28 days after surgery | baseline to 28 days after surgery, approx. 56 days | 
| Seriousness of adverse events (AE)/serious adverse events (SAE) | Overall tolerability by seriousness of AEs/SAEs until 28 days after surgery | baseline to 28 days after surgery, approx. 56 days | 
| Relationship of adverse events (AE)/serious adverse events (SAE) | Overall tolerability by relationship of AEs/SAEs until 28 days after surgery | baseline to 28 days after surgery, approx. 56 days | 
| Severity of adverse events (AE)/serious adverse events (SAE) | Overall tolerability by severity of AEs/SAEs until 28 days after surgery | baseline to 28 days after surgery, approx. 56 days | 
| Changes in Laboratory parameters | Changes White blood count on each visit | throughout study conduction, max 77 days | 
| Changes in Laboratory parameters | Changes in thrombocytes on each visit | throughout study conduction, max 77 days | 
| Changes in Laboratory parameters | Changes in serum creatinine on each visit | throughout study conduction, max 77 days | 
| Changes in Laboratory parameters | Changes in AST on each visit | throughout study conduction, max 77 days | 
| Changes in Laboratory parameters | Changes in ALT on each visit | throughout study conduction, max 77 days | 
| Changes in Laboratory parameters | Changes in gamma GT on each visit | throughout study conduction, max 77 days | 
| Changes in Laboratory parameters | Changes in phosphate on each visit | throughout study conduction, max 77 days | 
| Changes in vital signs | Changes in vital signs on each visit | throughout study conduction, max 77 days | 
| Changes in blood pressure | Changes in blood pressure on each visit | throughout study conduction, max 77 days | 
| Changes in heart rate | Changes in heart rate on each visit | throughout study conduction, max 77 days | 
| Changes in physical exam | Changes in physical exam on each visit | throughout study conduction, max 77 days | 
| adverse events related to administration | AEs related to injection/infusion site reactions (i.v. group only) | at baseline | 
| adverse events related to administration | AEs related to injection/infusion site reactions (i.v. group only) | 7 days after baseline, at Visit 3 | 
| hypersensitivity reactions | documentation of anaphylatic or anaphylactoid reactions (i.v. group only) | at baseline | 
| hypersensitivity reactions | documentation of anaphylatic or anaphylactoid reactions (i.v. group only) | at study visit 3 | 
| Mortality | All-cause mortality within 28 days after surgery | within 28 days after surgery, approx. 56 days | 
| Quality of Life (SF36) | Assessment of Quality of Life by SF36 questionnaire at visits 4 compared to BL | base line to visit 4 approx 35 days | 
| Quality of Life (SF36) | Assessment of Quality of Life by SF36 questionnaire at visits 5 compared to BL | baseline to visit 5 approx 70 days | 
| Duration of hospital stay | Duration of hospital stay (days) until 28 days after surgery | 28 days | 
| Number of patients with normalized Hb-values | Number of patients with normalized Hb-values after iron substitution (n, %) at visits 4 and 5 | baseline to visit 4 approx 35 days | 
| Number of patients with normalized Hb-values | Number of patients with normalized Hb-values after iron substitution (n, %) at and 5 | baseline to visit 5 approx 70 days | 
| Analysis of total iron levels | Analysis of total iron levels in plasma at BL after end of iron administration (for the i.v. groups (safety analysis group) only) | approx 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pre surgery iron treatment