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

Primary Purpose

Iron Deficiency Anemia

Status
Suspended
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Polyglucoferron
Ferric carboxymaltose
Ferrous Sulfate
Sponsored by
Dr. Frank Behrens
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron Deficiency Anemia focused on measuring pre surgery iron treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Polyglucoferron

Ferric Carboxymaltose

Ferrous sulfate

Arm Description

once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg

Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg)

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

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Units of allogenic red blood cell transfusion
Proportion of units of allogenic red blood cell transfusion from BL until visit 5
Hb values
Mean change in Hb at visit 4 compared to BL
Hb values
Mean change in Hb at visit 5 compared to BL
Transferrin Saturation (TSAT) values
Mean change in TSAT at visit 5 compared to BL
Transferrin Saturation (TSAT) values
Mean change in TSAT at visit 4 compared to BL
iron values
Mean change in serum iron at visit 4 compared to BL
iron values
Mean change in serum iron at visit 5 compared to BL
ferritin values
Mean change in serum ferritin at visit 5 compared to BL
ferritin values
Mean change in serum ferritin at visit 4 compared to BL
transferrin values
Mean change in serum ferritin at visit 4 compared to BL
transferrin values
Mean change in serum ferritin at visit 5 compared to BL
number of adverse events (AE)/serious adverse events (SAE)
Tolerability measured by overall number of AEs/SAEs until 28 days after surgery
incidence of adverse events (AE)/serious adverse events (SAE)
Tolerability by incidence of AEs/SAEs until 28 days after surgery
Seriousness of adverse events (AE)/serious adverse events (SAE)
Overall tolerability by seriousness of AEs/SAEs until 28 days after surgery
Relationship of adverse events (AE)/serious adverse events (SAE)
Overall tolerability by relationship of AEs/SAEs until 28 days after surgery
Severity of adverse events (AE)/serious adverse events (SAE)
Overall tolerability by severity of AEs/SAEs until 28 days after surgery
Changes in Laboratory parameters
Changes White blood count on each visit
Changes in Laboratory parameters
Changes in thrombocytes on each visit
Changes in Laboratory parameters
Changes in serum creatinine on each visit
Changes in Laboratory parameters
Changes in AST on each visit
Changes in Laboratory parameters
Changes in ALT on each visit
Changes in Laboratory parameters
Changes in gamma GT on each visit
Changes in Laboratory parameters
Changes in phosphate on each visit
Changes in vital signs
Changes in vital signs on each visit
Changes in blood pressure
Changes in blood pressure on each visit
Changes in heart rate
Changes in heart rate on each visit
Changes in physical exam
Changes in physical exam on each visit
adverse events related to administration
AEs related to injection/infusion site reactions (i.v. group only)
adverse events related to administration
AEs related to injection/infusion site reactions (i.v. group only)
hypersensitivity reactions
documentation of anaphylatic or anaphylactoid reactions (i.v. group only)
hypersensitivity reactions
documentation of anaphylatic or anaphylactoid reactions (i.v. group only)
Mortality
All-cause mortality within 28 days after surgery
Quality of Life (SF36)
Assessment of Quality of Life by SF36 questionnaire at visits 4 compared to BL
Quality of Life (SF36)
Assessment of Quality of Life by SF36 questionnaire at visits 5 compared to BL
Duration of hospital stay
Duration of hospital stay (days) until 28 days after surgery
Number of patients with normalized Hb-values
Number of patients with normalized Hb-values after iron substitution (n, %) at visits 4 and 5
Number of patients with normalized Hb-values
Number of patients with normalized Hb-values after iron substitution (n, %) at and 5
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)

Full Information

First Posted
August 29, 2019
Last Updated
March 11, 2020
Sponsor
Dr. Frank Behrens
Collaborators
University Hospital Frankfurt, Department of Anaesthesiology, IRON4U, University Hospital Frankfurt Institute for Biostatistics & Mathematical Modelling
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1. Study Identification

Unique Protocol Identification Number
NCT04087993
Brief Title
Polyglucoferron Compared to i.v. Ferric Carboxymaltose and Oral Iron Substitution in Preoperative Treatment of Iron Deficiency Anaemia in Patients
Acronym
IDA-I
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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Suspended
Why Stopped
difficult recruitment - redesign in discussion
Study Start Date
May 15, 2020 (Anticipated)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Frank Behrens
Collaborators
University Hospital Frankfurt, Department of Anaesthesiology, IRON4U, University Hospital Frankfurt Institute for Biostatistics & Mathematical Modelling

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Deficiency Anemia
Keywords
pre surgery iron treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
407 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Polyglucoferron
Arm Type
Experimental
Arm Description
once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg
Arm Title
Ferric Carboxymaltose
Arm Type
Active Comparator
Arm Description
Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg)
Arm Title
Ferrous sulfate
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Polyglucoferron
Other Intervention Name(s)
Feramyl
Intervention Description
intravenous administration
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Other Intervention Name(s)
Ferinject
Intervention Description
intravenous administration
Intervention Type
Drug
Intervention Name(s)
Ferrous Sulfate
Other Intervention Name(s)
Ferro sanol duodenal
Intervention Description
oral administration
Primary Outcome Measure Information:
Title
Normalisation or Increase of hemaglobin(Hb)-level
Description
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
Time Frame
baseline (BL) to day before surgery (visit 4)
Title
Detection of urine iron
Description
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
Time Frame
approx. 8 hours
Secondary Outcome Measure Information:
Title
Units of allogenic red blood cell transfusion
Description
Proportion of units of allogenic red blood cell transfusion from BL until visit 5
Time Frame
baseline to visit 5 approx. 70 day
Title
Hb values
Description
Mean change in Hb at visit 4 compared to BL
Time Frame
baseline to visit 4 approx. 35 day
Title
Hb values
Description
Mean change in Hb at visit 5 compared to BL
Time Frame
baseline to visit 5 approx. 70 day
Title
Transferrin Saturation (TSAT) values
Description
Mean change in TSAT at visit 5 compared to BL
Time Frame
baseline to visit 5 approx. 70 day
Title
Transferrin Saturation (TSAT) values
Description
Mean change in TSAT at visit 4 compared to BL
Time Frame
baseline to visit 4 approx. 35 day
Title
iron values
Description
Mean change in serum iron at visit 4 compared to BL
Time Frame
baseline to visit 4 approx. 35 day
Title
iron values
Description
Mean change in serum iron at visit 5 compared to BL
Time Frame
baseline to visit 5 approx. 70 day
Title
ferritin values
Description
Mean change in serum ferritin at visit 5 compared to BL
Time Frame
baseline to visit 5 approx. 70 day
Title
ferritin values
Description
Mean change in serum ferritin at visit 4 compared to BL
Time Frame
baseline to visit 4 approx. 35 day
Title
transferrin values
Description
Mean change in serum ferritin at visit 4 compared to BL
Time Frame
baseline to visit 4 approx. 35 day
Title
transferrin values
Description
Mean change in serum ferritin at visit 5 compared to BL
Time Frame
baseline to visit 5 approx. 70 day
Title
number of adverse events (AE)/serious adverse events (SAE)
Description
Tolerability measured by overall number of AEs/SAEs until 28 days after surgery
Time Frame
baseline to 28 days after surgery, approx. 56 days
Title
incidence of adverse events (AE)/serious adverse events (SAE)
Description
Tolerability by incidence of AEs/SAEs until 28 days after surgery
Time Frame
baseline to 28 days after surgery, approx. 56 days
Title
Seriousness of adverse events (AE)/serious adverse events (SAE)
Description
Overall tolerability by seriousness of AEs/SAEs until 28 days after surgery
Time Frame
baseline to 28 days after surgery, approx. 56 days
Title
Relationship of adverse events (AE)/serious adverse events (SAE)
Description
Overall tolerability by relationship of AEs/SAEs until 28 days after surgery
Time Frame
baseline to 28 days after surgery, approx. 56 days
Title
Severity of adverse events (AE)/serious adverse events (SAE)
Description
Overall tolerability by severity of AEs/SAEs until 28 days after surgery
Time Frame
baseline to 28 days after surgery, approx. 56 days
Title
Changes in Laboratory parameters
Description
Changes White blood count on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in Laboratory parameters
Description
Changes in thrombocytes on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in Laboratory parameters
Description
Changes in serum creatinine on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in Laboratory parameters
Description
Changes in AST on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in Laboratory parameters
Description
Changes in ALT on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in Laboratory parameters
Description
Changes in gamma GT on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in Laboratory parameters
Description
Changes in phosphate on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in vital signs
Description
Changes in vital signs on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in blood pressure
Description
Changes in blood pressure on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in heart rate
Description
Changes in heart rate on each visit
Time Frame
throughout study conduction, max 77 days
Title
Changes in physical exam
Description
Changes in physical exam on each visit
Time Frame
throughout study conduction, max 77 days
Title
adverse events related to administration
Description
AEs related to injection/infusion site reactions (i.v. group only)
Time Frame
at baseline
Title
adverse events related to administration
Description
AEs related to injection/infusion site reactions (i.v. group only)
Time Frame
7 days after baseline, at Visit 3
Title
hypersensitivity reactions
Description
documentation of anaphylatic or anaphylactoid reactions (i.v. group only)
Time Frame
at baseline
Title
hypersensitivity reactions
Description
documentation of anaphylatic or anaphylactoid reactions (i.v. group only)
Time Frame
at study visit 3
Title
Mortality
Description
All-cause mortality within 28 days after surgery
Time Frame
within 28 days after surgery, approx. 56 days
Title
Quality of Life (SF36)
Description
Assessment of Quality of Life by SF36 questionnaire at visits 4 compared to BL
Time Frame
base line to visit 4 approx 35 days
Title
Quality of Life (SF36)
Description
Assessment of Quality of Life by SF36 questionnaire at visits 5 compared to BL
Time Frame
baseline to visit 5 approx 70 days
Title
Duration of hospital stay
Description
Duration of hospital stay (days) until 28 days after surgery
Time Frame
28 days
Title
Number of patients with normalized Hb-values
Description
Number of patients with normalized Hb-values after iron substitution (n, %) at visits 4 and 5
Time Frame
baseline to visit 4 approx 35 days
Title
Number of patients with normalized Hb-values
Description
Number of patients with normalized Hb-values after iron substitution (n, %) at and 5
Time Frame
baseline to visit 5 approx 70 days
Title
Analysis of total iron levels
Description
Analysis of total iron levels in plasma at BL after end of iron administration (for the i.v. groups (safety analysis group) only)
Time Frame
approx 4 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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., 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kai Zacharowski, Prof. MD
Organizational Affiliation
University Hospital of Goethe-University Frankfurt
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University
City
Frankfurt
State/Province
Hessia
ZIP/Postal Code
60590
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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