Improved Recovery by Iron Following Surgery With Blood Loss, a Double-blind Multi-centre Randomized Controlled Phase III Drug Trial (the IRIS-trial)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 338
- 试验地点
- 1
- 主要终点
- Recovery after iv Iron
研究概览
简要总结
The aim of the study is to investigate if iv iron formulation improve recovery after surgery with blood loss.
Post-operative anaemia is a common debilitating condition after major surgery due to a combination of preoperative iron deficiency anaemia (IDA) and per-operative blood loss. Median blood loss following hepatopancreatobiliary (HPB) and complex aortic surgery typically range between 500-1000 ml. Bioavailability of iron may be a rate limiting factor in erythropoiesis in anaemia secondary to blood loss. For the IRIS trial, it is hypothesized that intravenously (iv) administered Ferric Carboxymaltose after a per-operative blood loss of 400-4000 ml, improves post-operative recovery and reduces the RBC transfusion.
Patients scheduled for elective HPB surgery or complex aortic surgery will be screened for eligibility and recruited into the study.
By the end of the surgical procedure, if blood loss is estimated to 400-4000 ml, the patient is randomized 1:1 to iv 1000 mg Ferric Carboxymaltose or placebo.
The primary endpoint is a composite of death, number of RBC transfusions, post-operative severe anemia (Hb <80 g/L) and FACT-An Quality of life (QoL) five weeks after surgery, assessed by win ratio.
The trial will also examine effects on; a) levels of Hb; b) markers of erythropoiesis and iron bioavailability; c) post-operative complications; d) post-operative recovery; e) performance status; f) subgroups based on type of surgery and degree of anemia and iron deficiency; g) re-admissions; h) long term outcome based on patient medical records and i) how post-operative recovery differs between those with low (<400 ml), high (400-4000 ml) and very high (>4000 ml) per-operative blood loss.
Recruitment will continue until 338 patients are randomized or 304 have completed the five week follow up
The coordinating center of the trial is the Department of Surgery at Uppsala University Hospital. Participating sites are also Linköping University Hospital and Lund University Hospital, all in Sweden. Other sites may be added.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The attending nurse at the postoperative ward will do the final preparation of study drug and thus be aware of which patient receives placebo or iv iron. As the Ferric Carboxymaltose solution is opaque, the study drug is kept concealed behind the patient. Most patients have amnesia of the first hours after general anaesthesia. This effect is more pronounced after long and complex surgery which is the case for all patients included in this trial. Blinding from the patent's perspective is therefore not expected to be a major concern. The personnel preparing the study drug and nurse at the postoperative ward does not participate in care beyond this point, ensuring blinding is maintained.
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
- •Provision of written informed consent
- •Male and female patients
- •Weight > 50 kg
- •> 18 years of age
- •Scheduled for complex aortic surgery, liver resection or pancreatic resection
排除标准
- •Short expected survival (less than six months)
- •Intra-venous iron therapy within one month prior to surgery
- •Severe anaemia (B-Hb <80 mg/L) prior to surgery
- •Contraindication to Ferric Carboxymaltose according to SmPC
- •Iron overloading disorder, i.e. hemochromatosis
- •Risk of small for size future liver remnant
- •Pre-operative renal replacement therapy
- •Enrolled in another drug or medical device study within 30 days prior to enrolment of the current study
- •Another planned major surgical procedure before the five week follow up
- •Unsuitable for inclusion according to the investigator
研究组 & 干预措施
Iv Iron
Ferric Carboxymaltose, single dose, Intra venous 1000 mg in 100 ml 0.9% NaCl
干预措施: Ferric carboxymaltose (Drug)
Placebo
Placebo, single dose, Intra venous 0.9% NaCl 100 ml
干预措施: Placebo (Drug)
结局指标
主要结局
Recovery after iv Iron
时间窗: Five weeks
To examine if 1000 mg iv Ferric Carboxymaltose administered immediately following hepatic or pancreatic resection or complex aortic surgery with 400 - 4000 ml perioperative blood loss affect a composite of death, number of RBC transfusions, prevalence of post-operative severe anaemia (Hb \< 80 g/L) and change in FACT-An QoL questionnaire score at five weeks after surgery compared to pre-operative baseline score. The composite endpoint is assessed by win ratio in the following order: Alive at five weeks (yes/no); number of RBC transfusions from surgery until five weeks; severe anaemia with Hb \<80 g/L any time after surgery until five weeks (yes/no); FACT-An score (score at five weeks minus score at baseline)
次要结局
- Performance status(Five weeks)
- Hb(One to five weeks)
- Complications(One to five weeks)
- Recovery(One to five weeks)
研究者
Jon Unosson
Principal Investigator
Uppsala University Hospital