Clinical trial NCT06012760: The Effect of Combined Iron Protocols on Perioperative Allogeneic Transfusion
Official title: Effect of Iron Sucrose Combined With Human Erythropoietin and Vitamin C on Perioperative Allogeneic Red Blood Cell Infusion in Major Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anemia
Iron Deficiency Anemia
Perioperative
Transfusion
Cardiac Surgery
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Wenzhou Medical University
name: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
name: The Central Hospital of Lishui City
name: First Affiliated Hospital of Chongqing Medical University
name: Zhejiang Provincial People's Hospital
name: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
name: Zhejiang University
name: Nanjing Hospital affiliated hospital of Nanjing medicine University
First posted: 2023-08-25
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if a combined iron supplementation regimen can reduce the need for blood transfusions in adults with iron-deficiency anemia undergoing major elective cardiac surgery. The trial will also look at whether this regimen is safe and well tolerated. The main questions it aims to answer are:

Does the combined regimen lower the amount of allogeneic red blood cell transfusion needed during and after surgery?

Are there any side effects or safety concerns associated with the regimen?

Researchers will compare the combined iron supplementation (sucrose iron, erythropoietin, and vitamin C) to standard care to see if it helps reduce blood transfusions.

Participants will:

Receive either the combined regimen or standard care before surgery

Undergo major elective cardiac surgery under general anesthesia

Be monitored for blood transfusion needs and recovery up to 90 days after surgery

Detailed description: 1. Hypothesis:The combined protocol of preoperative sucrose iron, human erythropoietin, and vitamin C will demonstrate superiority in reducing perioperative allogeneic red blood cell (RBC) transfusion volume compared to standard care in patients with iron deficiency anemia undergoing major cardiac surgery with cardiopulmonary bypass.
2. Interventions 2.1.Experimental group: Patients in the experimental group will receive a combination therapy consisting of intravenous sucrose iron (200 mg), subcutaneous recombinant human erythropoietin (150 IU/kg), and intravenous vitamin C (2 g), administered once daily for three consecutive days within the week prior to surgery.

   2.2.Control group: Routine perioperative management based on clinical judgment, including observation, monitoring, and standard nursing practices.
3. Primary endpoint: Total volume of allogeneic RBC transfusion (units) from surgery initiation to postoperative day 5.
4. Stratification in randomization: Stratification factors include types of surgery, preoperative baseline hemoglobin level.
5. Follow-up time important points include: baseline upon hospital admission, the morning of surgery, postoperative day 1, postoperative day 5, at discharge, 30 ± 7 days after surgery, and 90 ± 7 days after surgery.
6. All perioperative transfusion decisions will follow standardized restrictive transfusion thresholds. When the patient's hemoglobin concentration falls below the threshold of 70 g/L during surgery or ICU monitoring, or below 70-80 g/L in the general ward, and/or when signs of anemia or hemodynamic instability are present-including shock, severe arrhythmias, respiratory distress, heart rate \>120 beats/min, systolic blood pressure (SBP) \<80 mmHg, mean arterial pressure (MAP) \<55-60 mmHg, or a reduction in SBP or MAP exceeding 25% from baseline-these findings may indicate significant hypovolemia and warrant consideration of transfusion intervention.

Eligibility criteria: 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.

Primary outcomes:
measure: Perioperative allogeneic red blood cell transfusion volume
timeFrame: From the initiation of the surgical procedure until five days post-surgery.
Secondary outcomes:
measure: The quantity and percentage of allogeneic blood products utilized during the perioperative period.
timeFrame: From the initiation of the surgical procedure until until 90± 7 days following the surgical procedure.
measure: The alterations in perioperative haemoglobin levels.
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: The alterations in ferritin levels and TSAT during the perioperative period.
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: The alterations in reticulocyte levels during the perioperative period.
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: The score measuring the quality of life after surgery.
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: Incidence of perioperative complication within 90 days after major cardiac surgery
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: The mortality rate within 30-day and 90-day postoperative period.
timeFrame: Within 90± 7 days after surgery
measure: length of stay in hospital
timeFrame: Within 90± 7 days after surgery
measure: Length of stay in ICU
timeFrame: Within 90± 7 days after surgery
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University anesthesiology department
state: Zhejiang
Study officials:
References:
citation: Zeroual N, Blin C, Saour M, David H, Aouinti S, Picot MC, Colson PH, Gaudard P. Restrictive Transfusion Strategy after Cardiac Surgery. Anesthesiology. 2021 Mar 1;134(3):370-380. doi: 10.1097/ALN.0000000000003682.
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