Effect of the Combined Programme on Perioperative Anaemia（CPPA）

Effectiveness of Iron Sucrose Combined With rHuEPO and Ascorbic Acid in Improving Perioperative Anaemia in Patients Undergoing Major Cardiac Surgery

We used the preoperative intervention of iron sucrose in combination with human erythropoietin and vitamin C as an innovative combination therapy. This combined treatment strategy aims to improve perioperative anaemia in patients by promoting erythropoiesis and improving iron metabolism. Compared with previous perioperative intravenous iron supplementation, this innovative combination therapy strategy takes into account multiple aspects of iron metabolism as well as the biological mechanisms of erythropoiesis, providing a more comprehensive intervention. Management of perioperative anaemia in previous studies has largely relied on single intravenous iron supplementation therapy, and although this approach has been effective in raising iron levels, its effectiveness may be limited in patients who have impaired iron utilisation or in situations where concurrent stimulation of erythropoiesis is required. The use of iron sucrose in combination with human erythropoietin and vitamin C, on the other hand, is based on an integrative therapeutic concept aimed at providing a more comprehensive response to perioperative anaemia by simultaneously promoting effective iron utilisation and erythropoiesis.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Surgery; Iron Deficiency Anemia; Patient Blood Management
• Intervention / Treatment: Drug: Iron Sucrose, recombinant human erythropoietin, ascorbic acid; Procedure: conventional treatment

Detailed Description

Perioperative anaemia is one of the most common comorbidities in patients undergoing surgery, with a prevalence of up to 30% in patients undergoing cardiac surgery. Perioperative anaemia can lead to ischaemia and hypoxia in vital organs, increased postoperative complications and even increased mortality; in addition to an increased rate of allogeneic blood product transfusions and significantly longer ICU and hospital stays. Correcting perioperative anaemia and reducing complications are of great importance to improve the immediate and long-term prognosis of patients undergoing major cardiac surgery.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Min Yan; Phone Number: 13757118632; Email: zryanmin@zju.edu.cn

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years and above
• Ferritin <300µg/L, transferrin saturation <25%, male 90<Hb<130g/L or female 90<Hb<120g/L
• Elective major cardiac surgery (valve replacement, CABG coronary artery bypass surgery or a combination of both)
• ASA: Grade 1-3
• Signed informed consent

Exclusion Criteria:

1. Allergy or contraindication to iron sucrose or recombinant human erythropoietin or ascorbic acid
2. Patients with a preoperative temperature >37.5 °C or on non-prophylactic antibiotics
3. Pregnancy or breastfeeding stage
4. weight ≤ 50 kg
5. Presence of chronic renal insufficiency, urinary stones, oxalate deposits, gout
6. Chronic liver disease and/or screening alanine transferase/aspartate transferase above normal 3 times or more above the upper limit of the normal range
7. Family history of haemochromatosis, thalassaemia or transferrin saturation > 50%
8. Known history of iron overload
9. Other known causes of anaemia (folic acid or vitamin B12 deficiency or haemoglobinopathies, etc.)
10. Emergency surgery
11. Use of iron, blood transfusion or related anaemia treatment within 12 weeks prior to surgery

Withdrawal criteria:

1. massive blood transfusion (≥ 10 red blood cells (RBC)/24h)
2. Preoperative interventions not performed according to standard
3. Cancellation of surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iron treatment intervention arm; The combination therapy group will receive three treatments consisting of 200 mg/100 ml of iron sucrose IV infusion, 150 IU/Kg of erythropoietin subcutaneously and 2 mg/100 ml of vitamin C IV infusion in the week prior to surgery	Drug: Iron Sucrose, recombinant human erythropoietin, ascorbic acid; During the 1 week period following admission, 3 consecutive dosing regimens were administered, 200 mg of iron sucrose by intravenous infusion at 8am daily in combination with 150 IU/kg of recombinant human erythropoietin by subcutaneous injection and 2 g of ascorbic acid by intravenous infusion.
Active Comparator: conventional treatment arm; Treatment in accordance with measures routinely used by the surgeon's team to treat anemia including but not limited to (clinical observation, oral iron supplementation, intravenous iron supplementation, blood transfusion, or other measures) will be documented faithfully by the study team	Procedure: conventional treatment; Treatment in accordance with measures routinely used by the surgeon's team to treat anemia including but not limited to (clinical observation, oral iron supplementation, intravenous iron supplementation, blood transfusion, or other measures) will be documented faithfully by the study team

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemoglobin level on postoperative day 5	Haemoglobin level on postoperative day 5	Haemoglobin level on postoperative day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of allogeneic blood products used in the perioperative period	(red blood cells, plasma, platelets)	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Effect of combination therapy on changes in perioperative haemoglobin levels	Pre-intervention versus post-operative haemoglobin	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Effect of combination therapy on changes in perioperative ferritin levels	Pre-intervention versus post-operative ferritin	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Effect of combination therapy on changes in perioperative reticulocyte levels	Magnitude of reticulocyte elevation	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Incidence of perioperative acute renal insufficiency	Postoperative creatinine more than 2 times higher than preoperative or oliguria (<0.5ml/kg/h) within 12 hours	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Infusion reactions and allergies	Perioperative allergic events	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Incidence of serious adverse events (SAEs) in the perioperative period up to 6 months after surgery	Myocardial infarction、Ischemic cerebral infarction、arrhythmia、Deep vein thrombosis of the lower extremity、Pulmonary embolism, etc	Through study completion, an average of 1.5 year
All-cause mortality within 6 months of surgery	Incidence of mortality	Through study completion, an average of 1.5 year
Total length of hospital stay	Total length of hospital stay	Through study completion, an average of 1 year
Incidence of perioperative infections	Non-prophylactic use of antibiotics	Through study completion, an average of 1 year
Post-operative intensive care unit stay	Length of stay in ICU after surgery	From the start of surgery until hospital discharge or postoperative day 30, whichever comes first
Health Care Costs	All medical costs during hospitalisation	From admission until hospital discharge or postoperative day 30, whichever comes first
Post-operative hospital readmission rate	Post-operative hospital readmission rate	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Min Yan, Doctor, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 25, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Iron Metabolism Disorders; Anemia, Hypochromic; Iron Deficiencies; Anemia; Anemia, Iron-Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Antioxidants; Protective Agents; Vitamins; Hematinics; Epoetin Alfa; Ferric Oxide, Saccharated; Ascorbic Acid
• Other Study ID Numbers: 2022-0156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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