The Postoperative Iron in Cardiac Surgery (PICS-) Trial: A Randomised Clinical Trial Comparing the Efficacy of Single-, High-dose Intravenous Iron and Oral Iron for the Treatment of Anaemia Following Cardiac Surgery
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- The proportion of participants who are neither anemic nor have received allogeneic red blood cells since randomisation
研究概览
简要总结
BACKGROUND Anemia and iron deficiency are highly prevalent in cardiac surgery patients. Both conditions may adversely affect postoperative rehabilitation.
At hospital discharge, anemia is almost invariably present due to perioperative blood loss and frequent blood sampling. Two previous analyses demonstrated a prevalence of anemia early after coronary artery bypass grafting (CABG) of 94% and 98%, respectively. Almost half of CABG patients had persistent anemia two months after surgery. Postoperative anemia may result in debilitating symptoms, like dyspnoea, fatigue and poor exercise tolerance, and is associated with an increased likelihood of cardiovascular events and death after cardiac surgery.
Mild to moderate anemia is commonly corrected with oral iron supplements. Oral iron is however poorly absorbed in patients with chronic diseases, and about 40% of patients suffer from debilitating gastrointestinal side-effects. As iron stores are frequently reduced or depleted after cardiac surgery, treatment with oral iron supplements may take several months.
In patients with chronic heart failure (CHF), iron deficiency is associated with reduced exercise capacity, quality of life and survival even in the absence of anemia. Several large randomised trials demonstrated that treatment with intravenous iron improved clinical symptoms, exercise capacity and quality of life of CHF patients.
RATIONALE It is desirable to replenish body iron stores rapidly after cardiac surgery with the aim to effectively correct anemia, optimize exercise tolerance and improve patient wellbeing.
Modern intravenous iron formulations permit fast replenishment of body iron stores and have emerged as potential alternatives to oral iron. These formulations are well-tolerated and have become an established therapeutic option in anemic patients with reduced intestinal iron absorption. Several studies have demonstrated the efficacy of intravenous iron for the treatment of anemia following major non-cardiac surgery.
Data regarding the efficacy of intravenous iron in cardiac surgery, however, are conflicting.
HYPOTHESIS Single-dose intravenous iron therapy with ferric derisomaltose/iron isomaltoside is superior to oral iron supplementation for the correction of anemia following cardiac surgery. Moreover, single-dose intravenous iron therapy with ferric derisomaltose/iron isomaltoside results in a greater postoperative exercise capacity, an improved quality of life and less fatigue.
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
盲法说明
The study is primarily open label. It includes, however, a short period (from the 1. to the 4. postoperative day) of participant, care provider and investigator masking. The aim is to reduce differences in transfusion practices.
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 18 years of age or older undergoing first-time, non-emergent cardiac surgery with cardiopulmonary bypass. Eligible procedures are A: isolated CABG surgery (+/- arrhythmia surgery), B: isolated cardiac valve surgery (+/- arrhythmia surgery), C: a combination of CABG and cardiac valve surgery (+/- arrhythmia surgery)
- •Moderate anaemia on the first postoperative day. According to World Health Organization-criteria defined as a haemoglobin concentration of equal to or greater than 5.0 mmol/l (8 g/dl) and less than 6.8 mmol/l (11 g/dl).
排除标准
- •Known hypersensitivity to any iron formulation
- •Multiple drug allergies or history of previous anaphylaxis
- •Severe asthma, eczema or another atopic allergy
- •Rheumatoid arthritis or systemic lupus erythematosus
- •History of iron overload or disturbances in iron utilisation (e.g. haemochromatosis, hemosiderosis)
- •History of liver disease (e.g. cirrhosis)
- •Severe active infection or inflammation (e.g. endocarditis)
- •Porphyria cutanea tarda
- •Treatment with intravenous iron within 4 weeks prior to surgery.
- •Untreated vitamin B12 or folate deficiency.
- •Anticipated inability to perform a six-minute walk test.
- •Women of childbearing potential, pregnant and nursing women.
- •Anticipated postoperative length of stay in the intensive care unit (ICU) > 48 hours.
- •Patients incapable of giving consent personally.
- •Significantly increased risk of non-adherence or loss to follow-up.
- •Active participation in another interventional trial with potential impact on postoperative anaemia or exercise capacity.
研究组 & 干预措施
Intravenous iron group
Single-dose intravenous infusion of 20 mg/kg body weight ferric derisomaltose/iron isomaltoside 1000 (MonoFer®)
干预措施: Ferric Derisomaltose (Drug)
Oral iron group
Oral therapy with 100 mg oral ferrous sulfate twice daily
干预措施: Ferrous sulfate (Drug)
Oral iron group
Oral therapy with 100 mg oral ferrous sulfate twice daily
干预措施: normal saline (Drug)
结局指标
主要结局
The proportion of participants who are neither anemic nor have received allogeneic red blood cells since randomisation
时间窗: 4-week follow-up
Unit: percentage; anemia according to WHO criteria defined as hemoglobin \< 12 g/dl in women and \< 13 g/dl in men.
次要结局
- Mean haemoglobin level(4-week follow-up)
- Proportion of participants with a haemoglobin increase ≥ 1.3 mmol/l (≥ 2 g/dL)(From baseline to 4-week follow-up)
- Mean change in hemoglobin level(From baseline to 4-week follow-up)
- Mean reticulocyte count(4-week follow-up)
- Mean plasma iron(4-week follow-up)
- Mean plasma ferritin(4-week follow-up)
- Mean transferrin saturation(4-week follow-up)
- Mean change in haemoglobin level(From the day before surgery to 4-week follow-up)
- Mean change in plasma ferritin(From the day before surgery to 4-week follow-up)
- Mean change in reticulocyte count(From the day before surgery to 4-week follow-up)
- Mean change in plasma iron(From the day before surgery to 4-week follow-up)
- Mean change in transferrin saturation(From the day before surgery to 4-week follow-up)
- Proportion of participants transfused with allogeneic red blood cells(From the time of randomisation to 4-week follow-up)
- Six-minute walk distance(4-week follow-up)
- Health-related quality of life(4-week follow-up)
- Fatique(4-week follow-up)
- New York Heart Association (NYHA) functional class(4-week follow-up)
研究者
Michael Kremke
Principal Investigator
Aarhus University Hospital