Clinical trial NCT06968936: Perioperative Blood Conservation: Role of Combined Iron Supplementation Protocols in Reducing Allogeneic Transfusion
Official title: Short-term Preoperative Combined Iron, Erythropoietin, and Vitamin C Therapy in Patients With Iron-deficiency Anaemia Undergoing Elective Cardiac Surgery: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anemia
Iron Deficiencies
Cardiac Surgery
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Chongqing Medical University
name: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
name: The First Affiliated Hospital with Nanjing Medical University
name: First Affiliated Hospital of Wenzhou Medical University
name: Zhejiang Provincial People's Hospital
First posted: 2025-05-13
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Central stratified block group randomization
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. All perioperative transfusion decisions will follow standardized restrictive transfusion thresholds.

   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. Outcome assessors will be blinded to group allocation to reduce assessment bias.
6. Follow-up time 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.
7. 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: The volume of allogeneic red blood cell transfusions during the perioperative period.
timeFrame: From the initiation of the surgical procedure until five days post-surgery.
Secondary outcomes:
measure: Percentage of patients with any RBC transfusions
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: Combined allogeneic transfusions (RBC, FFP( fresh frozen plasma), platelets)
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: Perioperative Hb concentrations
timeFrame: Follow-up time 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.
measure: The alterations in ferritin levels and TSAT during the perioperative period.
timeFrame: 6.Follow-up time 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.
measure: The alterations in reticulocyte levels during the perioperative period.
timeFrame: 6.Follow-up time 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.
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: Acute kidney failure
timeFrame: From the initiation of the surgical procedure until 7 days post-surgery.
measure: Major Adverse Cardiac and Cerebrovascular Events (MACCE)
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: New atrial fibrillation
timeFrame: From the point of randomisation until 90± 7 days following the surgical procedure.
measure: Infections
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: Thrombotic and thromboembolic complications
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: 30 day and 90-day mortality
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: Costs (for blood products and pharmaceutical products related to transfusion and anemia management)
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: All serious adverse events
timeFrame: From the initiation of the surgical procedure until discharge. Perioperative
measure: Length of stay (LOS) in the hospital
timeFrame: Within 90± 7 days after surgery
measure: Length of stay in the intensive care unit (ICU)
timeFrame: Within 90± 7 days after surgery
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Department of Anesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References:
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