An Open-label, Multicentre, Randomised, 3-arm Study to Investigate the Comparative Efficacy and Safety of Intravenous Ferric Carboxymaltose (Ferinject High and Low Dosage Regimens) Versus Oral Iron for the Treatment of Iron Deficiency Anaemia in Subjects With Non-dialysis-dependent Chronic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 626
- 试验地点
- 19
- 主要终点
- Kaplan-Meier Survival Analysis for Time to Other Anemia Therapy or Hb Trigger
研究概览
简要总结
Phase IIIb study to evaluate the long-term efficacy of ferric carboxymaltose (FCM) (using targeted ferritin levels to determine dosing) or oral iron in non-dialysis-dependent chronic kidney disease (NDD-CKD) subjects with iron deficiency anaemia (IDA).
详细描述
After an initial screening period of up to 4 weeks, eligible subjects were randomised (1:1:2) to 1 of the following 3 treatment arms for a period of 52 weeks.
- FCM regimen (maximum single intravenous doses of 1,000 mg of iron) targeting a ferritin level of 400-600 mcg/L.
- FCM regimen (maximum single intravenous doses of 200 mg of iron) targeting a ferritin level of 100-200 mcg/L.
- Daily oral iron with 200 mg iron/day (100 mg twice daily)
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
- •At least 18 years of age.
- •NDD-CKD subjects with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 using modification of diet in renal disease 4 (MDRD-4) calculation.
- •NDD-CKD subjects with an eGFR loss ≤12 mL/min/1.73 m2/year and a predicted eGFR of ≥15 mL/min/1.73 m2 in 12 months.
- •Any single Hb between 9 and 11 g/dL within 4 weeks of randomisation. A value taken as part of routine medical care was used.
- •Any single serum ferritin <100 mcg/L or <200 mcg/L with TSAT <20% within 4 weeks of randomisation. Measurements taken as part of routine medical care were used.
- •ESA naïve; no exposure to ESA in last 4 months prior to randomisation.
- •Females of childbearing potential must have had a negative pregnancy test, using any medically acceptable assessment, prior to randomisation.
- •Before any study specific procedure, the appropriate written informed consent must have been obtained.
排除标准
- •History of acquired iron overload.
- •Known hypersensitivity reaction to any component of ferrous sulphate or FCM. Subjects with hypersensitivity to other forms of iron were permitted to participate.
- •Documented history of discontinuing oral iron products due to significant gastrointestinal (GI) distress.
- •Screening TSAT >40%.
- •Known active infection, C-reactive protein >20 mg/L, clinically significant overt bleeding, active malignancy (i.e., clinical evidence of current malignancy or not in stable remission for at least 5 years since completion of last treatment with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia).
- •History of chronic alcohol abuse (alcohol consumption >40 g/day).
- •Chronic liver disease and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of the normal range.
- •Active human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome or active hepatitis B or C virus infection.
- •Anaemia due to reasons other than iron deficiency (e.g., haemoglobinopathy). Subjects with treated Vitamin B12 or folic acid deficiency were permitted.
- •IV iron and/or blood transfusion in previous 30 days prior to screening (or during the screening period).
- •Oral iron therapy at doses >100 mg/day dosing must have been discontinued at least 1 week prior to randomisation. If subject had received this therapy for >3 months (at doses >100 mg/day) then subject was not eligible. Ongoing use of multivitamins containing iron was permitted.
- •Immunosuppressive therapy that may have led to anaemia (e.g., cyclophosphamide, azathioprine, or mycophenolate mofetil). Steroid therapy was permitted.
- •Currently requiring renal dialysis.
- •Anticipated dialysis or transplant during the study.
- •Anticipated need for surgery that may have resulted in significant bleeding (>100 mL).
- •Currently suffering from chronic heart failure New York Heart Association Class IV.
- •Poorly controlled hypertension (>160 mmHg systolic pressure or >100 mmHg diastolic pressure).
- •Acute coronary syndrome or stroke within the 3 months prior to screening.
- •Currently suffering from concomitant, severe psychiatric disorders or other conditions which, in the opinion of the Investigator, would have made participation unacceptable.
- •Subject was not using adequate contraceptive precautions.
- •Subject of childbearing potential was evidently pregnant (e.g., positive human chorionic gonadotropin test) or was breast feeding.
- •Body weight <35 kg.
- •Subject currently was enrolled in or had not yet completed at least 30 days since ending other investigational device or drug studies, or subject was receiving other investigational agent(s).
- •Subject would not be available for follow-up assessment.
- •Subject had any kind of disorder that compromised the ability of the subject to give written informed consent and/or to comply with study procedures.
研究组 & 干预措施
FCM (high ferritin target)
Ferric carboxymaltose (FCM) (Ferinject / Injectafer) targeting ferritin level of 400 - 600 mcg/L
干预措施: FCM (Ferric carboxymaltose) high ferritin target (Drug)
FCM (low ferritin target)
Ferric carboxymaltose (FCM) (Ferinject / Injectafer) targeting ferritin level of 100 - 200 mcg/L
干预措施: FCM (Ferric carboxymaltose) low ferritin target (Drug)
Oral Iron
Ferrous sulphate 100 mg iron twice daily, continuous
干预措施: Oral Iron (Ferrous sulphate) (Drug)
结局指标
主要结局
Kaplan-Meier Survival Analysis for Time to Other Anemia Therapy or Hb Trigger
时间窗: Up to 1 year after baseline
Endpoint reported number of participants with/without events and was reached: * First time of initiation of additional or alternative anaemia management, * First time the subject reached the Hb trigger. 3 primary comparisons using a hierarchical step-down procedure on the log-rank test to preserve an alpha level of 0.05, performed in the following order: 1. FCM (high ferritin target) compared with oral iron. 2. FCM (high ferritin target) compared with FCM (low ferritin target). 3. FCM (low ferritin target) compared with oral iron. Sensitivity analyses of the primary endpoint were performed using the following alternative definitions of time to initiation of additional or alternative anaemia management: 1. Without taking into account the Hb trigger. 2. Taking into account the Hb trigger based on local laboratory data, instead of central laboratory data. 3. Taking into account the Hb trigger based on subjects with a complete set of Hb values from the central laboratory.
次要结局
未报告次要终点