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)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Normalisation or Increase of hemaglobin(Hb)-level
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Polyglucoferron
once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg
干预措施: Polyglucoferron (Drug)
Ferric Carboxymaltose
Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg)
干预措施: Ferric carboxymaltose (Drug)
Ferrous sulfate
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
干预措施: Ferrous Sulfate (Drug)
结局指标
主要结局
Normalisation or Increase of hemaglobin(Hb)-level
时间窗: baseline (BL) to day before surgery (visit 4)
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
时间窗: approx. 8 hours
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
次要结局
- Units of allogenic red blood cell transfusion(baseline to visit 5 approx. 70 day)
- Hb values(baseline to visit 5 approx. 70 day)
- Transferrin Saturation (TSAT) values(baseline to visit 4 approx. 35 day)
- ferritin values(baseline to visit 4 approx. 35 day)
- transferrin values(baseline to visit 5 approx. 70 day)
- number of adverse events (AE)/serious adverse events (SAE)(baseline to 28 days after surgery, approx. 56 days)
- incidence of adverse events (AE)/serious adverse events (SAE)(baseline to 28 days after surgery, approx. 56 days)
- Seriousness of adverse events (AE)/serious adverse events (SAE)(baseline to 28 days after surgery, approx. 56 days)
- Number of patients with normalized Hb-values(baseline to visit 5 approx 70 days)
- Analysis of total iron levels(approx 4 hours)
- iron values(baseline to visit 5 approx. 70 day)
- Relationship of adverse events (AE)/serious adverse events (SAE)(baseline to 28 days after surgery, approx. 56 days)
- Severity of adverse events (AE)/serious adverse events (SAE)(baseline to 28 days after surgery, approx. 56 days)
- Changes in Laboratory parameters(throughout study conduction, max 77 days)
- Changes in vital signs(throughout study conduction, max 77 days)
- Changes in blood pressure(throughout study conduction, max 77 days)
- Changes in heart rate(throughout study conduction, max 77 days)
- Changes in physical exam(throughout study conduction, max 77 days)
- adverse events related to administration(7 days after baseline, at Visit 3)
- hypersensitivity reactions(at study visit 3)
- Mortality(within 28 days after surgery, approx. 56 days)
- Quality of Life (SF36)(baseline to visit 5 approx 70 days)
- Duration of hospital stay(28 days)
研究者
Dr. Frank Behrens
Sponsor representative
Fraunhofer Institute for Molecular Biology and Applied Ecology