Polyglucoferron Compared to i.v. Ferric Carboxymaltose and Oral Iron Substitution in Preoperative Treatment of Iron Deficiency Anaemia in Patients (IDA-I)

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)

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.

Study Overview

• Status: Suspended
• Conditions: Iron Deficiency Anemia
• Intervention / Treatment: Drug: Polyglucoferron; Drug: Ferric carboxymaltose; Drug: 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 Type: Interventional
• Enrollment (Anticipated): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hessia
    • Frankfurt, Hessia, Germany, 60590
      • Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyglucoferron; once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg	Drug: Polyglucoferron; intravenous administration; Other Names: Feramyl
Active Comparator: 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)	Drug: Ferric carboxymaltose; intravenous administration; Other Names: Ferinject
Active Comparator: 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	Drug: Ferrous Sulfate; oral administration; Other Names: Ferro sanol duodenal

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr. Frank Behrens
• Collaborators: University Hospital Frankfurt, Department of Anaesthesiology; IRON4U; University Hospital Frankfurt Institute for Biostatistics & Mathematical Modelling
• Investigators: Principal Investigator: Kai Zacharowski, Prof. MD, University Hospital of Goethe-University Frankfurt

Study record dates

Study Major Dates

• Study Start (Anticipated): May 15, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: pre surgery iron treatment
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases
• Other Study ID Numbers: TMP0916_02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No