Postoperative i.v. Iron Substitution in Patients With Diagnosed Iron Deficiency

Iron Deficiency Anemia Clinical Trial

— IDA-II  

Official title:

Safety and Efficacy of Postoperative i.v. Iron Substitution With Polyglucoferron Compared to Ferric Carboxymaltose and Oral Iron in Patients With Diagnosed Iron Deficiency Who Develop Anaemia Peri- or Postoperatively (IDA II)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03817957
• Other study ID #: TMP0916_03
• Status: Recruiting
• Phase: Phase 3
• Start date: September 18, 2018
• Est. completion date: December 2022

Study information

• Verified date: November 2021
• Source: Fraunhofer Institute for Molecular Biology and Applied Ecology
• Contact: Anita Bulczak-Schadendorf, Phd
• Phone: 0049696301
• Email: anita.bulczak-schadendorf[@]ime.fraunhofer.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Iron deficiency anaemia (IDA) in postoperative patients with confirmed preoperative iron deficiency (ID) in a population with planned major surgery who need fast replenishment of iron as judged by the treating physician will be treated with i.v. iron using Polyglucoferron, Ferric Carboxymaltose or oral iron

Description:

In this study, patients with confirmed and documented preoperative non-anaemic iron deficiency (diagnosis up to 28 days before surgery in routine pre-surgery monitoring) who develop anaemia within 12 to 72 hours after start of surgery (with additional confirmation at Baseline) and for whom fast replenishment of iron stores is necessary, will be included and substituted within 24h after Screening Visit/V1. Peri- or postoperative anaemia will be assessed as soon as possible but earliest 12 h after surgery. For short term safety analysis iron in urine will be measured in the first urine after the end of i.v. administration in the first 35 patients who are eligible for analysis in each i.v. treatment group. Only those patients are eligible for whom haematuria and/or proteinuria are excluded using dip stick test. The Ferric Carboxymaltose treatment arm will be closed if a sufficient number of patients is included for safety analysis.The study will then be continued for assessment of co-primary efficacy endpoint: The effectiveness of postoperative i.v. iron substitution with Polyglucoferron compared to conventional oral iron substitution with Ferrous sulfate (treatment 28 - 35 days) to normalize Hb-values or to increase Hb-values by at least 1.5 g/dl until visit 4 will be evaluated as well as patient related outcomes, such as the decreased need for allogenic blood transfusions. In addition, the well-being of the patient will be assumed to improve after treatment using the SF36 questionnaire.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 407
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males or female; aged = 18 years

• Patients after major surgery (e.g., orthopaedic/trauma, vascular, visceral, cardiac surgery) with risk of Hb reduction and/or blood loss who develop anaemia defined as haemoglobin of <12 g/dL for female and <13 g/dL for men within 12 to 72 h after start of surgery and with confirmation at Baseline

• Confirmed and documented preoperative iron deficiency defined as S-ferritin <100 ng/mL without anaemia (Hb =12 g/dL for female and =13 g/dL for male) within 28 days before surgery

• need for fast iron replenishment as judged by the treating physician

• Written informed consent; willing/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 physical inability, e.g., American society of anesthesiologists (ASA) physical status IV or V

• Patients receiving blood transfusion 24 week prior surgery

• 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 main study period

• Patients with hemodynamic instability due to any ongoing bleeding. Absence of ongoing bleeding will be confirmed determined either by decision of two independent physicians or by removal of drainage, whichever occurs earlier in routine care)

• Patients with any contraindication to the investigational products, e.g.,

1. known sensitivity to iron or an ingredient of the investigational products

2. Significant 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

• 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 Summary of product characteristics (SmPC)

2. hypersensitivity to the active substance, to Ferric Carboxymaltose 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

1. hypersensitivity to any ingredient in the formulation

2. known serious hypersensitivity to other parenteral iron products

3. anaemia not attributed to iron deficiency

4. evidence of iron overload or disturbances in the utilisation of iron

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• 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	Proportion of patients who achieve normalized Hb-levels or increased Hb of at least 1.5 g/dl	Proportion of patients in the Polyglucoferron i.v. arm compared to oral iron substitution with Ferrous sulfate at visit 4 compared to Baseline (BL)	Baseline to approximately 30 days post-baseline (visit 4)
Primary	pre post difference of volumen-corrected urine iron levels	Pre-post difference of volume-corrected urine iron levels measured before and 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, compared between Polyglucoferron and Ferric Carboxymaltose (volume corrected iron urine is defined as the ratio between urine iron and urine creatinine).	urine sampled prior to administration and approximately 1 to 8 hours post-baseline
Secondary	Proportion of patients with normalization of Hemoglobin (Hb) at visit 4	measurement of normalization of Hb defined in World Health Organization (WHO) classification	30 days after baseline (Visit 4)
Secondary	Level of Hb until visit 4	determination of levels of Hemoglobin (Hb) (comparison to baseline)	Baseline to 30 days after baseline (visit 4)
Secondary	Level of Transferrin Saturation (TSAT) until visit 4	determination of levels of Transferrin Saturation (TSAT) (mean values in comparison to baseline)	Baseline to 30 days after baseline (visit 4)
Secondary	Level of serum-iron until visit 4	determination of levels of serum-iron (mean values in comparison to baseline)	Baseline to 30 days after baseline (visit 4)
Secondary	Level of serum-transferrin until visit 4	determination of levels of serum-transferrin (mean values in comparison to baseline)	Baseline to 30 days after baseline (visit 4)
Secondary	Level of serum-ferritin until visit 4	determination of levels of serum-ferritin (mean values in comparison to baseline)	Baseline to 30 days after baseline (visit 4)
Secondary	Value of serum-phosphate levels at visit 4 (i.v. groups only)	measurement of serum-phosphate levels (mean values in comparison to baseline)	baseline and 30 days after baseline (visit 4)
Secondary	Overall tolerability and number, incidence, seriousness, severity, relationship of Adverse Events (AE) and serious adverse events (SAE) until 30 days after Investigational medicinal product (IMP) administration	determination of number, incidence, seriousness, severity and causality of adverse events and serious adverse events	baseline to 30 days after last IMP administration
Secondary	Level of c-reactive protein on each available visit	Documentation of values of C reactive protein (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of ALT on each available visit	Documentation of values of ALT (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of AST on each available visit	Documentation of values of AST (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of gamma-glutamyltransferase on each available visit	Documentation of values of gamma-glutamyltransferase (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of urea nitrogen on each available visit	Documentation of values of urea nitrogen (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of serum creatinine on each available visit	Documentation of values of serum creatinine (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of white blood cells on each available visit	Documentation of values of white blood cells (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Values of thrombocytes on each available visit	Documentation of values of thrombocytes (description of changes in values in comparison to baseline)	baseline to 30 days after baseline (visit 4)
Secondary	Changes in systolic blood pressure on each available visit	Documentation of vital signs as systolic blood pressure	baseline to 30 days after baseline (visit 4)
Secondary	Changes in body temperature on each available visit	Documentation of body temperature	baseline to 30 days after baseline (visit 4)
Secondary	Changes in pulse rate on each available visit	Documentation of pulse rate	baseline to 30 days after baseline (visit 4)
Secondary	Changes in diastolic blood pressure on each available visit	Documentation of vital signs as diastolic blood pressure	baseline to 30 days after baseline (visit 4)
Secondary	Assessment of general conditions on each available visit	Documentation of clinical assessments of general condition will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of Skin on each available visit	Documentation of clinical assessments of Skin will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of eyes on each available visit	Documentation of clinical assessments of eyes will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of ears on each available visit	Documentation of clinical assessments of ears will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of mouth on each available visit	Documentation of clinical assessments of mouth will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of nose on each available visit	Documentation of clinical assessments of nose will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of throat on each available visit	Documentation of clinical assessments of throat will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of cardiovascular system on each available visit	Documentation of clinical assessments of cardiovascular system will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of respiratory system on each available visit	Documentation of clinical assessments of respiratory system,will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of abdomen on each available visit	Documentation of clinical assessments of abdomen will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of gastrointestinal tract on each available visit	Documentation of clinical assessments of gastrointestinal tract will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	clinical assessments of kidneys on each available visit	Documentation of clinical assessments of kidneys will be made by investigator - changes to preceding visits and in comparison to baseline will be documented	baseline to 30 days after baseline (visit 4)
Secondary	AEs related to injection/ infusion site reactions (i.v. treatment arms only) and hypersensitivity reactions	Documentation of numbers of adverse events related to injection/infusion site reactions (i.v. treatment arms only) and hypersensitivity reactions	baseline to 30 days after last IMP administration
Secondary	Number of deaths from any cause until visit 4	documentation of number of deaths	baseline to 30 days after baseline (visit 4)
Secondary	Proportion of units of allogenic red blood cell transfusion from BL until visit 4	Documentation of number of units of allogenic red blood cell transfusion	Baseline to 30 days after baseline (visit 4)
Secondary	Proportion of patients with need of allogenic red blood cell transfusion from BL until visit 4	Documentation of the use of allogenic red blood cell transfusion	Baseline to 30 days after baseline (visit 4)
Secondary	treatment effect on change in Quality of Life (SF36) at visit 4 compared to BL	documentation of quality of life in the Short Form Health Survey (SF36) with 36 items relying upon patient self-reporting. It contains eight sections: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. The SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Baseline to 30 days after baseline (visit 4)
Secondary	Duration of hospital stay (days) until visit 4	documentation of days in hospital	Baseline to 30 days after baseline (visit 4)
Secondary	Level ofl iron in plasma after end of iron administration (for the i.v. groups (safety analysis group) only)	measurement of iron level in plasma	time points directly after administration of intravenous (i.v.) treatment (approximately 15 minutes post-baseline)
Secondary	Level of iron in plasma after urine sampling (for the i.v. groups (safety analysis group) only)	measurement of iron level in plasma	time points after urine sampling (approximately 1 to 8 hours post-baseline)