The Effect of Combined Iron Protocols on Perioperative Allogeneic Transfusion (CIPAT)

Effect of Iron Sucrose Combined With Human Erythropoietin and Vitamin C on Perioperative Allogeneic Red Blood Cell Infusion in Major Cardiac Surgery

Previous studies have shown that perioperative intravenous iron has a beneficial effect on patients with perioperative anaemia. To assess whether a combined iron supplementation regimen can reduce perioperative allogeneic blood transfusions in patients with iron deficiency anaemia undergoing major cardiac surgery under haemodynamic anaesthesia, a multicentre randomised clinical trial (CIPAT study) will be conducted. In the CIPAT study, patients undergoing elective major cardiac surgery under general anaesthesia will be randomly allocated to a control group and a combined iron supplementation group. Patients in the combined iron supplementation group will receive a combination iron supplementation regimen of iron sucrose in combination with Human Erythropoietin and vitamin C three times in the week prior to surgery, while patients in the control group will receive the same dose of placebo three times in the week prior to surgery. The primary endpoint is the volume of allogeneic erythrocyte infusion from the start of surgery to 5 days postoperatively. It is hypothesised that patients in the combined iron supplementation group will have fewer perioperative allogeneic red blood cell transfusions than those in the control group.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Cardiac Surgery; Iron Deficiency Anemia; Perioperative; Transfusion
• Intervention / Treatment: Drug: Iron sucrose, Human Erythropoietin Injection, Vitamin C; Drug: Standard Medical Care

Detailed Description

The objective of this study is to examine the potential of iron sucrose in conjunction with human erythropoietin and vitamin C to mitigate the need for perioperative allo-erythrocyte infusion in patients undergoing their initial elective major cardiac surgery. This will be achieved by assessing outcome measures including the quantity of perioperative allo-erythrocyte transfusion and the alteration in perioperative haemoglobin levels.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University anesthesiology department
      • Principal Investigator: Min Yan, Doctor
      • Contact: Min Yan, Doctor; Phone Number: 15888210247; Email: zryanmin@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be at least 18 years of age.
2. Major cardiac surgery should encompass procedures such as coronary artery bypass grafting (CABG), valve surgery, or a combination of both.
3. Iron deficiency anemia is defined as having a ferritin level below 100 μg/L or a ferritin level below 300 μg/L accompanied by a transferrin saturation below 25%. Additionally, hemoglobin levels should range between 90 and 130 g/L for men or between 90 and 120 g/L for women.
4. The American Society of Anesthesiologists (ASA) classification should fall within Grade 1-3.
5. Prior to participation, the patient or their legal representative must provide informed consent.

Exclusion Criteria:

1. Contraindications for the administration of iron sucrose, ascorbic acid, or rHuEPO.
2. Presence of a temperature exceeding 37.5 °C or the utilization of non-prophylactic antibiotics.
3. Individuals with a weight equal to or less than 50kg.
4. Individuals with a family history of haemochromatosis or thalassaemia, or those with a transferrin saturation level exceeding 50% or a documented history of iron overload.
5. Presence of other known haematological disorders such as folic acid or vitamin B12 deficiency, haemolytic anaemia, haemoglobinopathies, iron granulocytic anaemia, G6PD deficiency, etc.
6. Requirement for emergency surgical intervention.
7. Severe hepatic or renal impairment, ALT >3 times the upper limit of normal value or AST >3 times the upper limit of normal value, creatinine >1.5 times the upper limit of normal value
8. Pregnant or lactating women
9. history of blood transfusion, intravenous iron or ascorbic acid use within 12 weeks prior to surgery
10. Acute blood loss, gastrointestinal bleeding, etc. in the preoperative period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined Iron Protocols group（CIP group）; Preoperative randomization was conducted, followed by a three-day regimen in the week preceding surgery, involving the administration of intravenous iron sucrose at a dosage of 200 mg per day, vitamin C at a dosage of 2 g per day, and subcutaneous administration of Human Erythropoietin Injection at a dosage of 150 IU per kilogram.	Drug: Iron sucrose, Human Erythropoietin Injection, Vitamin C; The participants were administered a combined iron supplementation regimen consisting of iron sucrose,Human Erythropoietin Injection, and vitamin C, three times throughout the preoperative week.
Active Comparator: Standard Medical Care group（SMC group）; Standard Medical Care (SMC) for the treatment of IDA. SMC as determined by the Investigator for the treatment of iron deficiency anemia (IDA).	Drug: Standard Medical Care; Standard Medical Care (SMC) for the treatment of IDA. SMC as determined by the Investigator for the treatment of iron deficiency anemia (IDA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative allogeneic red blood cell transfusion volume	The volume of allogeneic red blood cell transfusions during the perioperative period.	From the initiation of the surgical procedure until five days post-surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The quantity and percentage of allogeneic blood products utilized during the perioperative period.	This encompasses blood components such as plasma and platelets, erythrocytes.	From the initiation of the surgical procedure until the patient's release from the hospital or the 30th day following the operation, whichever occurs earlier.
The alterations in perioperative haemoglobin levels.	Haemoglobin levels were assessed at various time intervals.	From the point of randomisation until 90± 7 days following the surgical procedure.
The alterations in ferritin levels and serum total iron binding capacity during the perioperative period.	Ferritin and serum total iron binding capacity values were assessed at various time intervals.	From the point of randomisation until 90± 7 days following the surgical procedure.
The alterations in reticulocyte levels during the perioperative period.	Reticulocyte levels were measured at various time intervals.	From the point of randomisation until 90± 7 days following the surgical procedure.
NYHA classification of cardiac function	NYHA classification of cardiac function values were assessed at various time intervals.	From the point of randomisation until 90± 7 days following the surgical procedure.
The score measuring the quality of life after surgery.	The findings are presented based on the EQ VAS score (0-100), which reflects the overall self-assessed health status. A higher score indicates a better health status. Additionally, the results are reported using the EQ-5D-3L Effectiveness Index (EQ-5D-3L) values (5-15), where a lower EQ-5D-3L value signifies a better state of health.	The time intervals of 30±7 days and 90±7 days were observed following the surgical procedure.
Incidence of perioperative complication within 90 days after major cardiac surgery	The potential postoperative complications within a 90-day timeframe encompass myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), serious adverse events (SAE), congestive heart failure, respiratory failure, and various infections.	Within 90 days after surgery
The mortality rate within a 90-day postoperative period.	The mortality rate within a 90-day postoperative period.	Within 90 days after surgery
length of stay in hospital	he time period from admission to the hospital to discharge	through study completion, an average of 14 days
Length of stay in ICU	The time period from admission to ICU after surgery to move out from ICU to normal ward	through study completion, an average of 4 days

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: The Central Hospital of Lishui City; First Affiliated Hospital of Wenzhou Medical University; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: August 22, 2023
• First Submitted That Met QC Criteria: August 22, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Iron Deficiencies; Hematinics; Epoetin Alfa; Ferric Oxide, Saccharated
• Other Study ID Numbers: A2023519

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Other researchers could email us to ask the data information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No