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

Overview

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.

Interventions

• 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.
• 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).

Primary outcome measures

• Perioperative allogeneic red blood cell transfusion volume [Time frame: From the initiation of the surgical procedure until five days post-surgery.]

Secondary outcome measures (9)

• The quantity and percentage of allogeneic blood products utilized during the perioperative period. [Time frame: From the initiation of the surgical procedure until until 90± 7 days following the surgical procedure.]
• The alterations in perioperative haemoglobin levels. [Time frame: From the point of randomisation until 90± 7 days following the surgical procedure.]
• The alterations in ferritin levels and TSAT during the perioperative period. [Time frame: From the point of randomisation until 90± 7 days following the surgical procedure.]
• The alterations in reticulocyte levels during the perioperative period. [Time frame: From the point of randomisation until 90± 7 days following the surgical procedure.]
• The score measuring the quality of life after surgery. [Time frame: From the point of randomisation until 90± 7 days following the surgical procedure.]
• Incidence of perioperative complication within 90 days after major cardiac surgery [Time frame: From the point of randomisation until 90± 7 days following the surgical procedure.]
• The mortality rate within 30-day and 90-day postoperative period. [Time frame: Within 90± 7 days after surgery]
• length of stay in hospital [Time frame: Within 90± 7 days after surgery]
• Length of stay in ICU [Time frame: Within 90± 7 days after surgery]

Eligibility criteria

Inclusion criteria

• Participants must be at least 18 years of age.
• Major cardiac surgery should encompass procedures such as coronary artery bypass grafting (CABG), valve surgery, or a combination of both.
• 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.
• The American Society of Anesthesiologists (ASA) classification should fall within Grade 1-3.
• Prior to participation, the patient or their legal representative must provide informed consent.

Exclusion criteria

• Contraindications for the administration of iron sucrose, ascorbic acid, or rHuEPO.
• Presence of a temperature exceeding 37.5 °C or the utilization of non-prophylactic antibiotics.
• Individuals with a weight equal to or less than 50kg.
• 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.
• Presence of other known haematological disorders such as folic acid or vitamin B12 deficiency, haemolytic anaemia, haemoglobinopathies, iron granulocytic anaemia, G6PD deficiency, etc.
• Requirement for emergency surgical intervention.
• 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
• Pregnant or lactating women
• history of blood transfusion, intravenous iron or ascorbic acid use within 12 weeks prior to surgery
• Acute blood loss, gastrointestinal bleeding, etc. in the preoperative period.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Zhejiang University anesthesiology department — Hangzhou

Publications

• 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. PMID 33475735
• Fowler AJ, Ahmad T, Abbott TEF, Torrance HD, Wouters PF, De Hert S, Lobo SM, Rasmussen LS, Della Rocca G, Beattie WS, Wijeysundera DN, Pearse RM; International Surgical Outcomes Study Group. Association of preoperative anaemia with postoperative morbidity and mortality: an observational cohort study in low-, middle-, and high-income countries. Br J Anaesth. 2018 Dec;121(6):1227-1235. doi: 10.1016/ PMID 30442249
• Carson JL, Brittenham GM. How I treat anemia with red blood cell transfusion and iron. Blood. 2023 Aug 31;142(9):777-785. doi: 10.1182/blood.2022018521. PMID 36315909
• Spahn DR, Schoenrath F, Spahn GH, Seifert B, Stein P, Theusinger OM, Kaserer A, Hegemann I, Hofmann A, Maisano F, Falk V. Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial. Lancet. 2019 Jun 1;393(10187):2201-2212. doi: 10.1016/S0140-6736(18)32555-8. Epub 2019 Apr 26. PMID 31036337
• Attallah N, Osman-Malik Y, Frinak S, Besarab A. Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis. 2006 Apr;47(4):644-54. doi: 10.1053/j.ajkd.2005.12.025. PMID 16564942

Identifiers

NCT: NCT06012760 · A2023519

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗