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

Iron Deficiency Anemia Clinical Trial

— 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)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04087993
• Other study ID #: TMP0916_02
• Status: Suspended
• Phase: Phase 3
• Start date: May 15, 2020
• Est. completion date: December 31, 2020

Study information

• Verified date: March 2020
• Source: Fraunhofer Institute for Molecular Biology and Applied Ecology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 407
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Deficiency Diseases
• Iron Deficiency Anemia

Intervention

Drug:
• Polyglucoferron
intravenous administration
• Ferric carboxymaltose
intravenous administration
• Ferrous Sulfate
oral administration

Locations

Country	Name	City	State
Germany	Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University	Frankfurt	Hessia

Sponsors (4)

Lead Sponsor	Collaborator
Dr. Frank Behrens	IRON4U, University Hospital Frankfurt Institute for Biostatistics & Mathematical Modelling, University Hospital Frankfurt, Department of Anaesthesiology

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	Hb values	Mean change in Hb at visit 4 compared to BL	baseline to visit 4 approx. 35 day
Secondary	Hb values	Mean change in Hb at visit 5 compared to BL	baseline to visit 5 approx. 70 day
Secondary	Transferrin Saturation (TSAT) values	Mean change in TSAT at visit 5 compared to BL	baseline to visit 5 approx. 70 day
Secondary	Transferrin Saturation (TSAT) values	Mean change in TSAT at visit 4 compared to BL	baseline to visit 4 approx. 35 day
Secondary	iron values	Mean change in serum iron at visit 4 compared to BL	baseline to visit 4 approx. 35 day
Secondary	iron values	Mean change in serum iron at visit 5 compared to BL	baseline to visit 5 approx. 70 day
Secondary	ferritin values	Mean change in serum ferritin at visit 5 compared to BL	baseline to visit 5 approx. 70 day
Secondary	ferritin values	Mean change in serum ferritin at visit 4 compared to BL	baseline to visit 4 approx. 35 day
Secondary	transferrin values	Mean change in serum ferritin at visit 4 compared to BL	baseline to visit 4 approx. 35 day
Secondary	transferrin values	Mean change in serum ferritin at visit 5 compared to BL	baseline to visit 5 approx. 70 day
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes in Laboratory parameters	Changes White blood count on each visit	throughout study conduction, max 77 days
Secondary	Changes in Laboratory parameters	Changes in thrombocytes on each visit	throughout study conduction, max 77 days
Secondary	Changes in Laboratory parameters	Changes in serum creatinine on each visit	throughout study conduction, max 77 days
Secondary	Changes in Laboratory parameters	Changes in AST on each visit	throughout study conduction, max 77 days
Secondary	Changes in Laboratory parameters	Changes in ALT on each visit	throughout study conduction, max 77 days
Secondary	Changes in Laboratory parameters	Changes in gamma GT on each visit	throughout study conduction, max 77 days
Secondary	Changes in Laboratory parameters	Changes in phosphate on each visit	throughout study conduction, max 77 days
Secondary	Changes in vital signs	Changes in vital signs on each visit	throughout study conduction, max 77 days
Secondary	Changes in blood pressure	Changes in blood pressure on each visit	throughout study conduction, max 77 days
Secondary	Changes in heart rate	Changes in heart rate on each visit	throughout study conduction, max 77 days
Secondary	Changes in physical exam	Changes in physical exam on each visit	throughout study conduction, max 77 days
Secondary	adverse events related to administration	AEs related to injection/infusion site reactions (i.v. group only)	at baseline
Secondary	adverse events related to administration	AEs related to injection/infusion site reactions (i.v. group only)	7 days after baseline, at Visit 3
Secondary	hypersensitivity reactions	documentation of anaphylatic or anaphylactoid reactions (i.v. group only)	at baseline
Secondary	hypersensitivity reactions	documentation of anaphylatic or anaphylactoid reactions (i.v. group only)	at study visit 3
Secondary	Mortality	All-cause mortality within 28 days after surgery	within 28 days after surgery, approx. 56 days
Secondary	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
Secondary	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
Secondary	Duration of hospital stay	Duration of hospital stay (days) until 28 days after surgery	28 days
Secondary	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
Secondary	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
Secondary	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