Clinical trial NCT04087993: Polyglucoferron Compared to i.v. Ferric Carboxymaltose and Oral Iron Substitution in Preoperative Treatment of Iron Deficiency Anaemia in Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Iron Deficiency Anemia
Keywords: pre surgery iron treatment
Lead sponsor: Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
Sponsor class: OTHER
Collaborators: name: University Hospital Frankfurt, Department of Anaesthesiology
name: IRON4U
name: University Hospital Frankfurt Institute for Biostatistics & Mathematical Modelling
First posted: 2019-09-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Normalisation or Increase of hemaglobin(Hb)-level
timeFrame: baseline (BL) to day before surgery (visit 4)
measure: Detection of urine iron
timeFrame: approx. 8 hours
Secondary outcomes:
measure: Units of allogenic red blood cell transfusion
timeFrame: baseline to visit 5 approx. 70 day
measure: Hb values
timeFrame: baseline to visit 4 approx. 35 day
measure: Hb values
timeFrame: baseline to visit 5 approx. 70 day
measure: Transferrin Saturation (TSAT) values
timeFrame: baseline to visit 5 approx. 70 day
measure: Transferrin Saturation (TSAT) values
timeFrame: baseline to visit 4 approx. 35 day
measure: iron values
timeFrame: baseline to visit 4 approx. 35 day
measure: iron values
timeFrame: baseline to visit 5 approx. 70 day
measure: ferritin values
timeFrame: baseline to visit 5 approx. 70 day
measure: ferritin values
timeFrame: baseline to visit 4 approx. 35 day
measure: transferrin values
timeFrame: baseline to visit 4 approx. 35 day
measure: transferrin values
timeFrame: baseline to visit 5 approx. 70 day
measure: number of adverse events (AE)/serious adverse events (SAE)
timeFrame: baseline to 28 days after surgery, approx. 56 days
measure: incidence of adverse events (AE)/serious adverse events (SAE)
timeFrame: baseline to 28 days after surgery, approx. 56 days
measure: Seriousness of adverse events (AE)/serious adverse events (SAE)
timeFrame: baseline to 28 days after surgery, approx. 56 days
measure: Relationship of adverse events (AE)/serious adverse events (SAE)
timeFrame: baseline to 28 days after surgery, approx. 56 days
measure: Severity of adverse events (AE)/serious adverse events (SAE)
timeFrame: baseline to 28 days after surgery, approx. 56 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in Laboratory parameters
timeFrame: throughout study conduction, max 77 days
measure: Changes in vital signs
timeFrame: throughout study conduction, max 77 days
measure: Changes in blood pressure
timeFrame: throughout study conduction, max 77 days
measure: Changes in heart rate
timeFrame: throughout study conduction, max 77 days
measure: Changes in physical exam
timeFrame: throughout study conduction, max 77 days
measure: adverse events related to administration
timeFrame: at baseline
measure: adverse events related to administration
timeFrame: 7 days after baseline, at Visit 3
measure: hypersensitivity reactions
timeFrame: at baseline
measure: hypersensitivity reactions
timeFrame: at study visit 3
measure: Mortality
timeFrame: within 28 days after surgery, approx. 56 days
measure: Quality of Life (SF36)
timeFrame: base line to visit 4 approx 35 days
measure: Quality of Life (SF36)
timeFrame: baseline to visit 5 approx 70 days
measure: Duration of hospital stay
timeFrame: 28 days
measure: Number of patients with normalized Hb-values
timeFrame: baseline to visit 4 approx 35 days
measure: Number of patients with normalized Hb-values
timeFrame: baseline to visit 5 approx 70 days
measure: Analysis of total iron levels
timeFrame: approx 4 hours
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University
state: Hessia
Study officials:
affiliation: University Hospital of Goethe-University Frankfurt
name: Kai Zacharowski, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: