Short-term Intravenous Iron Isomaltose Anhydride for IDA

• ClinicalTrials.gov Identifier: NCT03915327
• Recruitment Status: Not yet recruiting
• First Posted: April 16, 2019
• Last Update Posted: March 8, 2022
• Sponsor: West China Hospital
• Information provided by (Responsible Party): Ren Liao, West China Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Iron Deficiency Anemia	Drug: Intravenous iron isomaltose anhydride	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Short-term Use of Intravenous Iron Isomaltose Anhydride for Preoperative Anemic Patients Undergoing Orthopedic Surgery: a Prospective, Randomized, Controlled Study
• Estimated Study Start Date: March 5, 2022
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: May 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intravenous iron group; Enrolled subjects would receive intravenous iron isomaltose anhydride within 24 hours of the subject's inclusion.	Drug: Intravenous iron isomaltose anhydride; Enrolled subjects would receive intravenous iron isomaltose anhydride within 24 hours of the subject's inclusion.
No Intervention: Control group; Clinical management, including surgical procedures, anesthesia, and perioperative management, are performed in accordance with standard clinical practice.

Outcome Measures

Primary Outcome Measures :

1. Rate of allogeneic RBC transfusion [ Time Frame: 30 days after randomization ]
   Number of patients who receive allogeneic RBC transfusion/total number of patients.

Secondary Outcome Measures :

1. Average number of units of RBC transfused in patients who receive allogeneic RBC transfusion [ Time Frame: 30 days after randomization ]
   Total number of units of RBC transfused/number of patients who receive allogeneic RBC transfusion
2. Average number of units of RBC transfused in the entire study population [ Time Frame: 30 days after randomization ]
   Total number of units of RBC transfused/total number of patients
3. Incidence of postoperative adverse events (AEs) [ Time Frame: 30 days after randomization ]

   AEs are graded according to the severity:

   Grade 1 Recovery after temporary treatment, such as postoperative nausea and vomiting (PONV), urinary retention, anxiety, temporary insomnia, etc.

   Grade 2 Results in prolonged hospitalization, such as lung infections requiring antibiotic treatment, incision infections requiring debridement treatment, etc.; Grade 3 life-threatening, recovery after treatment during hospitalization, such as acute renal failure requiring renal replacement therapy, postoperative hemorrahge requiring surgical intervention, respiratory failure requiring mechanical ventilation, etc.; Grade 4 Injury last 30 days or more after surgery, a significant decrease in the quality of life, such as acute myocardial infarction, stroke, etc.; Grade 5 Death with 30 days after surgery

4. Hemoglobin (Hb) levels [ Time Frame: 30 days after randomization ]
   Hemoglobin (Hb) levels at different time points;
5. Length of stay (LOS) [ Time Frame: 30 days after randomization ]
   Length of stay (LOS), defined as number of days from admission to discharge
6. Postoperative hospital stay [ Time Frame: 30 days after randomization ]
   Number of days from the day of surgery to discharge
7. Re-admission [ Time Frame: 30 days after randomization ]
   Re-admission within 30 days after surgery
8. Cost of Hospitalization [ Time Frame: 30 days after randomization ]
   Total cost of hospitalization from admission to discharge.

Eligibility Criteria

• Ages Eligible for Study: 14 Years to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Ren Liao, M.D.; +86-18980602177; liaoren7733@163.com

Sponsors and Collaborators

West China Hospital

Investigators

• Principal Investigator: Ren Liao, M.D.; Department of Anesthesiology, West China Hospital, Sichuan University

More Information

• Responsible Party: Ren Liao, Associate Professor, West China Hospital
• ClinicalTrials.gov Identifier: NCT03915327
• Other Study ID Numbers: WCH20190308
• First Posted: April 16, 2019
• Last Update Posted: March 8, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data could be accessed under request to Dr. Ren Liao by email: liaoren7733@163.com
• Supporting Materials: Study Protocol
• Time Frame: From May 01,2023, for 10 years.
• Access Criteria: Contact with Dr. Ren Liao by email: liaoren7733@163.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ren Liao, West China Hospital:

Iron-deficiency anemia; Intravenous iron isomaltose anhydride; Preoperative

Additional relevant MeSH terms:

Anemia, Iron-Deficiency; Anemia; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Metabolic Diseases