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

Phase 3

Withdrawn

• Conditions: Iron Deficiency Anemia
• Interventions: Drug: Ferrous Sulfate; Drug: Polyglucoferron; Drug: Ferric carboxymaltose

• Registration Number: NCT04087993
• Lead Sponsor: Dr. Frank Behrens

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.

Study Timeline

• Study First Submitted: 2019-08-29
• Study First Submitted QC: 2019-09-10
• Study First Posted: 2019-09-12
• Study Start: 2020-05-15
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-27
• Last Update Posted: 2024-08-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

• Exclusion criteria related to Ferrous sulfate

  1. according to summary of product characteristics (SmPC)
  2. hypersensitivity to any ingredient in the formulation
  3. concomitant parenteral iron
  4. haemochromatosis, and other iron overload syndromes

• Exclusion criteria related to Ferric Carboxymaltose:

  1. according to SmPC
  2. hypersensitivity to the active substance, to Ferinject or any of its excipients
  3. known serious hypersensitivity to other parenteral iron products
  4. anaemia not attributed to iron deficiency
  5. evidence of iron overload or disturbances in the utilisation of iron

• Exclusion criteria related to Polyglucoferron f) hypersensitivity to any ingredient in the formulation

  1. known serious hypersensitivity to other parenteral iron products
  2. anaemia not attributed to iron deficiency
  3. evidence of iron overload or disturbances in the utilisation of iron

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ferrous sulfate	Ferrous Sulfate	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
Polyglucoferron	Polyglucoferron	once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg
Ferric Carboxymaltose	Ferric carboxymaltose	Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 5 approx. 70 day	Mean change in Hb at visit 5 compared to BL
Transferrin Saturation (TSAT) values	baseline to visit 4 approx. 35 day	Mean change in TSAT at visit 4 compared to BL
ferritin values	baseline to visit 4 approx. 35 day	Mean change in serum ferritin at visit 4 compared to BL
transferrin values	baseline to visit 5 approx. 70 day	Mean change in serum ferritin at visit 5 compared to BL
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
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
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
iron values	baseline to visit 5 approx. 70 day	Mean change in serum iron at visit 5 compared to BL
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 in phosphate on each visit
Changes in vital signs	throughout study conduction, max 77 days	Changes in vital signs on each visit
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	7 days after baseline, at Visit 3	AEs related to injection/infusion site reactions (i.v. group only)
hypersensitivity reactions	at study visit 3	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)	baseline to visit 5 approx 70 days	Assessment of Quality of Life by SF36 questionnaire at visits 5 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 5 approx 70 days	Number of patients with normalized Hb-values after iron substitution (n, %) at 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)

Trial Locations

Locations (1)

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University; 🇩🇪 Frankfurt, Hessia, Germany