E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
preoperative iron deficiency anaemia in patients with planned elective non-cardiac surgery |
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E.1.1.1 | Medical condition in easily understood language |
iron anaemia in patients with planned elective non-cardiac surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022974 |
E.1.2 | Term | Iron deficiency anemia |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) To demonstrate superiority of i.v. iron substitution with Polyglucoferron compared to oral iron therapy with Ferrous sulfate in focus on proportion of patients who achieve normalized Hb-levels (according to WHO definition) or an increased Hb of at least 1.5 g/dl at day before surgery compared to BL
2) To demonstrate superiority in short term safety assessed by measurements of statistically significant lower levels of urine iron after i.v. administration of Polyglucoferron compared to Ferric Carboxymaltose, measured in the first urine after the end of i.v. administration |
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E.2.2 | Secondary objectives of the trial |
-Need of allogenic red blood cell transfusion (number of units and number of patients) from BL until 28 days after surgery -Treatment effects on haematologic and serologic iron parameters (Hb, TSAT, s-iron, s-ferritin, s-transferrin) from baseline (BL) until day before surgery (V4) and V5 -Overall tolerability and number, incidence, seriousness, severity and relationship of AEs/SAEs until 28 days after surgery -Changes in laboratory parameters, vital signs and physical exam on each visit including blood pressure and heart rate -AEs related to injection/infusion site reactions (i.v. groups only) and hypersensitivity reaction -All-cause mortality within 28 days after surgery -Treatment effect on Quality of Life (SF36) at V4 and V5 compared to BL -Duration of hospital stay until 28 days after surgery -Number of patients with normalized Hb-values after iron substitution (n, %) at V4 and V5 -Analysis of total iron levels in plasma at BL after end of i.v. iron administration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female; aged ≥ 18 years 2.Planned to undergo elective 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 3.Iron deficiency defined as s-ferritin <100 ng/mL and s-transferrin saturation <20% 4.Relevant anaemia defined as haemoglobin of <12 g/dL for female and <13 g/dL for men 5.Written informed consent; willing and able to comply with the protocol
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E.4 | Principal exclusion criteria |
1.Pregnancy in female patients or breastfeeding women 2.Female patients not willing to use a safe method of contraception (PEARL index <1) for the full study period 3.Severe anaemia with Hb 8 g/dL 4.Any ingoing bleeding as judged by the treating physician 5.Patients receiving blood transfusion 24 weeks prior screening 6.Severe physical inability, e.g., ASA physical status IV or V 7.Haematuria and proteinuria of unknown or known origin 8.Non-iron deficiency anaemia, e.g., known Vitamin B12 or folate deficiency, haemoglobinopathy, or unexplained anaemia 9.Anticipated medical need for erythropoesis-stimulating agents during the study period 10.Patients with any contraindication to the investigational products, e.g., a)known sensitivity to iron or an ingredient of the investigational products b)History of systemic allergic reactions c)Haemachromatosis, thalassemia or TSAT >50% as indicator of iron overload d)Acute or chronic intoxication e)Infection (patient on non-prophylactic antibiotics) f)Chronic liver disease and/or screening ALT or AST above three times the upper limit of the normal range 11.Chronic kidney disease, defined as GFR <30 mL/min 12.S-Creatinine > 150 µmol/L 13.Active uncontrolled immune-mediated diseases such as rheumatoid arthritis or inflammatory bowel disease 14.Primary haematologic disease 15.Drug or alcohol abuse according to WHO definition 16.Potentially unreliable patients, and those judged by the investigator to be unsuitable for the study 17.Current or previous participation in another clinical trial during the last 90 days before screening
18.Exclusion criteria related to Ferrous sulfate a)according to SmPC b)hypersensitivity to any ingredient in the formulation c)concomitant parenteral iron d)haemochromatosis, and other iron overload syndromes
19.Exclusion criteria related to Ferric Carboxymaltose: a)according to SmPC b)hypersensitivity to the active substance, to Ferinject or any of its excipients c)known serious hypersensitivity to other parenteral iron products d)anaemia not attributed to iron deficiency e)evidence of iron overload or disturbances in the utilisation of iron
20.Exclusion criteria related to Polyglucoferron a)hypersensitivity to any ingredient in the formulation b)known serious hypersensitivity to other parenteral iron products c)anaemia not attributed to iron deficiency d)evidence of iron overload or disturbances in the utilisation of iron
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Proportion of patients achieving normalized Hb-levels (according to WHO definition) or an increase of at least 1.5 g/dl Hb at day before surgery (visit 4) compared to BL in the Polyglucoferron treatment arm compared to oral iron substitution
2) 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
V4 (day before surgery) and BL/V2 (28-35 days before surgery) |
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E.5.2 | Secondary end point(s) |
Secondary endpoints for efficacy: - Proportion of units of allogenic red blood cell transfusion from BL until visit 5 - Mean change in Hb, TSAT, s-iron, s-ferritin and s-transferrin at vistis 4 and 5 compared to BL
Secondary endpoints for safety: - Overall tolerability and number, incidence, seriousness, severity, and relationship of AEs/SAEs until 28 days after surgery (visit 5) - Changes in laboratory parameters, vital signs, and physical exam on each visit including blood pressure and heart rate - AEs related to injection/infusion site reactions (i.v. groups only) and hypersensitivity reactions - All-cause mortality within 28 days after surgery
Exploratory efficacy endpoints: - Quality of Life (SF36) at visits 4 and 5 compared to BL - Duration of hospital stay (days) until 28 days after surgery - Number of patients with normalized Hb-values after iron substitution (n, %) at visits 4 and 5 - Analysis of total iron levels in plasma at BL after end of iron administration (for the i.v. groups (safety analysis group) only) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
BL (28-35 days before surgery), V4 (day before surgery), V5 (28-35 days after surgery) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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closure of last study site |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |