Ferric Carboxymaltose Assessment of Morbidity and Mortality in Patients with IRon Deficiency and Chronic Heart Failure
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,105
- 试验地点
- 51
- 主要终点
- Time-to-first event of CV death or HF hospitalisation
研究概览
简要总结
The purpose of this study is to determine whether intravenous iron supplementation using ferric carboxymaltosis (FCM) extends the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death and reduces hospitalisation and mortality in patients with iron deficiency and heart failure.
详细描述
The clinical trial is designed as an international, prospective, multi-centre, double-blind, parallel group, randomised, controlled, interventional trial to investigate whether a long-term therapy with i.v. iron (ferric carboxymaltosis) compared to placebo can extend the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death (in the full population and in the population of patients with TSAT<20%) and reduce the rate of recurrent events of heart failure hospitalisations.
I.v. iron administration in the form of ferric carboxymaltosis (FCM) will be carried out according to the Summary of Product Characteristics (SmPC). Bolus administration (1000 mg) will be followed by an optional administration of 500-1000 mg within the first 4 weeks (up to a total of 2000 mg which is in-label) according to approved dosing rules, followed by administration of 500 mg FCM at every 4 months, except when haemoglobin is > 16.0 g/dL or ferritin is > 800 µg/L.
In the verum group, all patients will receive a saline administration, when no iron is indicated at the time of the visit and according to the values listed above. Patients originally assigned to the placebo group will receive a saline administration at all visits.
In the control group i.v. NaCl at a volume according to the dosing rules for FCM at all visits will be administered in a double-blind manner.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Patients with chronic HFrEF (CHF) of at least 3 months duration and a history of documented LVEF<45%.
- •Confirmed presence of ID (ferritin < 100 ng/mL or ferritin 100 - 299 ng/mL with TSAT < 20 %)
- •Serum haemoglobin of 9.5 - 14.0 g/dL
- •At time of screening considered re-stabilised and planned for discharge within next 24 h (NYHA 2 or 3), or stable ambulatory with a HF hospitalisation in the past 12 months (NYHA 2-4), or stable ambulatory with BNP > 100 pg/mL or NT-proBNP > 300 pg/mL or MR-proANP > 120 pmol/L (NYHA 2-4)
- •Written informed consent
排除标准
- •Hypersensitivity to the active substance, to FCM or any of its excipients
- •Known serious hypersensitivity to other parenteral iron products
- •Anaemia not attributed to iron deficiency, e.g. other microcytic anaemia
- •Evidence of iron overload or disturbances in the utilisation of iron
- •History of severe asthma with known FEV1 <50%
- •Acute bacterial infection
- •Presence of a deficiency for vitamin B12 and/or serum folate (if present, this needs to be corrected first)
- •Use of renal replacement therapy
- •Treatment with an erythropoietin stimulating agent (ESA), any i.v. iron and/or a blood transfusion in the previous 6 weeks prior to randomisation.
- •More than 500 meters in the initial 6-minutes walking-test
研究组 & 干预措施
Verum group (FCM)
I.v. iron administration in the form of FCM will be carried out according to SmPC. I.v. iron bolus administration (1000 mg) will be followed by an optional administration of 500-1000 mg within the first 4 weeks, (up to a total of 2000 mg which is in-label), according to the approved dosing rules, followed by administration of 500 mg FCM at every 4 months, except when haemoglobin is > 16.0 g/dL or ferritin is > 800 µg/L .In the verum group, all patients will receive a saline administration, when no iron is indicated at the time of the visit and according to the values listed above.
干预措施: Iron (Drug)
Placebo group (NaCL)
Administration of i.v. NaCl at a volume according to the dosing rules for FCM, i.e. as described for the verum group.
干预措施: Saline (Drug)
结局指标
主要结局
Time-to-first event of CV death or HF hospitalisation
时间窗: The whole follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.
Show that treatment of patients with systolic heart failure (HF) and iron deficiency (ID) with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) can extend the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death. Type I error rate control across the three primary endpoints will be ensured by using the Hochberg procedure.
Rate of total (first and recurrent) events of hospitalisations for heart failure (HF)
时间窗: The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.
Show that treatment of patients with systolic heart failure (HF) and iron deficiency (ID) with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) reduces the rate of recurrent events of heart failure hospitalisations.
Time-to-first event of CV death or HF hospitalisation in patients with TSAT <20%
时间窗: During the wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.
Show that treatment of patients with systolic heart failure (HF) and iron deficiency (ID) with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) can extend the time-to-first-event of heart failure hospitalisations and cardiovascular (CV) death in the population of patients with TSAT\<20%.
次要结局
- Changes in 6-minute walk-test (nomogram)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in NYHA (New York Heart Association) functional class (scale)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in EQ-5D (questionnaire)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in Patient Global Assessment (PGA) of wellbeing (questionnaire)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in renal parameters (laboratory parameters)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in cardiovascular parameters (laboratory parameters)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in inflammatory parameters (laboratory parameters)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Changes in metabolic parameters (laboratory parameters)(The wohle follow-up period. We aim for a minimum average follow-up of >2 years. We aim for a minimum follow-up of 6 months for all patients, but not less than 3 months.)
- Key Safety Endpoint: cardiovascular mortality(36 months of follow-up)
- Key Safety Endpoint: All-cause mortality(36 months of follow-up)