Clinical trial NCT03915327: Short-term Intravenous Iron Isomaltose Anhydride for IDA
Official title: Short-term Use of Intravenous Iron Isomaltose Anhydride for Preoperative Anemic Patients Undergoing Orthopedic Surgery: a Prospective, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Iron Deficiency Anemia
Keywords: Iron-deficiency anemia
Intravenous iron isomaltose anhydride
Preoperative
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2019-04-16
Enrollment: 1600
Sex: ALL
Minimum age (years): 14
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This prospective, randomized, controlled study aims to evaluate the impact of short-term intravenous iron isomaltose anhydride on postoperative recovery and the requirement for allogeneic red blood cells (RBC) transfusion in preoperative Iron-deficiency anemia (IDA) patients receiving orthopedic surgery, thus facilitating developing a simple and effective iron supplement approach for patients' recovery.

Detailed description: Anemia is a decrease in the concentration of hemoglobin (Hb) or RBC count in the blood ting, causing body not being able to adequately supply oxygen to tissues and cells. Preoperative anemia is common in patients receiving elective surgery, with a prevalence ranging from 5% to 75%. For instance, the prevalence of anemia before total hip or total knee arthroplasty is around 35%. Preoperative anemia is one of the main predictors of perioperative allogeneic RBC transfusion, and is closely associated with postoperative infection, increased morbidity and mortality, prolonged hospital stay, and decreased quality of life.

As the world enters an aging society, the proportion of elderly patients receiving surgery, especially orthopedic surgery, is increasing. There are 3 main causes of anemia in the elderly: nutritional anemia (\~34%), which is caused by lack of hematopoietic materials. Iron-deficiency anemia (IDA) is the most common type of nutritional anemia, while megaloblastic anemia caused by lack of folic acid and vitamin B12 is relatively rare. Anemia of chronic disease (\~32%), which is characterized by disorders of iron metabolism that occurs in certain chronic diseases, such as persistent infections, inflammation and tumors. Anemia of unknown cause (-34%), which may involve multifactorial pathogenic mechanisms and comorbidities. IDA, the most common cause of perioperative anemia in patients receiving orthopedic surgery, is a condition caused by hematopoietic materials deficiency and has a good clinical response to iron supplementation with a rapid rise of Hb level. Iron supplementation in patients with preoperative IDA, or insufficient iron intake and excessive loss is able to improve the patients' surgical tolerance and reduce the transfusion rate; For anemic patients with acute blood loss during surgery, iron supplementation is able to accelerate anemia correction, thus enhancing postoperative recovery and shortening length of hospital stay.

Iron therapy can be administrated by the oral or intravenous route. Absorption of oral iron therapy is relatively low, and it usually takes over 1 to 2 months to correct the iron deficiency status. Therefore, intravenous iron therapy is recommended for patients diagnosed with IDA after admission to hospital to receive surgery. Intravenous iron therapy was originally the standard iron supplementation in chronic renal failure patients with IDA. Subsequently, it was expanded to the anemia of patients with conventional inflammatory bowel disease for its desirable efficacy. Several studies of elderly IDA patients receiving orthopedic surgery and gynecologic surgery suggest that intravenous iron therapy can rapidly increase hemoglobin levels before surgery, leading to a decrease in blood transfusion rates. The calculation of the total dose of intravenous iron is as follows:

= Weight (kg) ×\[Target Hb level（g/L）- actual Hb level（g/L）\] ×0.24 + 500mg Treatment duration is over 2 weeks in most clinical studies of intravenous iron therapy. In China, few patients are treated with intravenous iron therapy in community hospitals for 2 to 4 weeks before surgery. Therefore, many IDA patients did not receive proper preoperative intravenous iron therapy. Iron isomaltose anhydride, an intravenous iron preparation that can be administered in a single treatment up to 1000 mg in a relatively short (15 minutes) time without need for test dose, is of low risk of adverse reactions. Therefore, sufficient amount of iron can be administrated during preoperative. Currently, there is no evidence to elucidate whether short-term sufficient intravenous iron supplementation can reduce perioperative blood transfusion requirements among IDA patients. Thus, we hypothesized that short-term intravenous administration of sufficient iron isomaltose anhydride can reduce the need for perioperative allogeneic RBC transfusion without increasing the incidence of adverse reactions.

This prospective, randomized, controlled study aims to evaluate the impact of short-term (1 week) intravenous iron isomaltose anhydride in preoperative IDA patients receiving orthopedic surgery on postoperative allogeneic RBC transfusion rate and amount, hemoglobin level and iron storage, postoperative complications, average length/expense of hospital stay, etc., to determine the safety and efficacy of short-term sufficient intravenous iron therapy, and to develop a simple and effective preoperative iron supplementation program.

Eligibility criteria: Inclusion Criteria:

* Age \> 14 years;
* Sign and date the "informed consent form"

Exclusion Criteria:

* Pregnant or lactation;
* Drug abuse, including but not limited to opioids, amphetamines, ice, ketamine, etc.;
* History of anaphylaxis to oral or intravenous iron;
* Nervous system diseases such as peripheral neuropathy, mental illness;
* Other conditions that the investigator deems are not suitable for the study, such as deafness, Parkinson's disease, communication disorders, etc.;
* Participated in other clinical trials during the first three months of the study.

Primary outcomes:
measure: Rate of allogeneic RBC transfusion
timeFrame: 30 days after randomization
Secondary outcomes:
measure: Average number of units of RBC transfused in patients who receive allogeneic RBC transfusion
timeFrame: 30 days after randomization
measure: Average number of units of RBC transfused in the entire study population
timeFrame: 30 days after randomization
measure: Incidence of postoperative adverse events (AEs)
timeFrame: 30 days after randomization
measure: Hemoglobin (Hb) levels
timeFrame: 30 days after randomization
measure: Length of stay (LOS)
timeFrame: 30 days after randomization
measure: Postoperative hospital stay
timeFrame: 30 days after randomization
measure: Re-admission
timeFrame: 30 days after randomization
measure: Cost of Hospitalization
timeFrame: 30 days after randomization
Other outcomes:
Locations:
Study officials:
affiliation: Department of Anesthesiology, West China Hospital, Sichuan University
name: Ren Liao, M.D.
role: PRINCIPAL_INVESTIGATOR
References: