The Effect of Intravenous Iron Therapy and Erythropoiesis-stimulation Agent Combination on Renal Transplant Outcomes

NCT05719376 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 4-2022-1314
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 1

Brief Summary

RBC transfusion (RBCT) after kidney transplantation(KT) is about 50%. Anemia is common after kidney transplant surgery due to intraoperative blood loss, delayed graft function, and side effects of immunosuppressive drugs. However, due to exposure to non-self human leukocyte antigens (HLA) from blood transfusion, there is a risk of sensitization to HLA through the production of anti-HLA antibodies. In renal transplant patients, exposure to non-self HLA antigens due to RBCT can lead to the generation of donor-specific antibodies (DSA) against renal allograft donors. Patients who have undergone KT are frequently exposed to RBCT, and immunologic damage resulting from this can be an important cause of loss of graft kidney function. Therefore, there should be a more careful review of the risk associated with RBCT on KT recipients. Of the 16,191 Koreans who underwent KT between 2008 and 2017, 59.7% received transplant-related blood transfusions. As a result of analyzing 13,871 Koreans who underwent KT between 2007 and 2015, the overall graft failure rate was 15.5%, and the hazard ratio of survival rate according to RBCT before and after KT increased as the amount of transfusion increased. RBCT before and after KT was independently associated with graft failure and death. Therefore, research on treatment methods that can effectively reduce blood transfusion in transplant patients is absolutely necessary. About 30-60% of patients undergoing major surgery show preoperative anemia, which causes blood transfusions, complications during hospitalization, prolonged hospitalization, and delayed recovery. The most common cause of anemia is iron deficiency. In particular, an increase in hepcidin, a major regulator of iron metabolism, reduces intestinal iron absorption and promotes iron sequestering by macrophages, resulting in a state of functional iron deficiency. Therefore, oral iron intake as a treatment for anemia in surgical patients is not effective. Although the safety and clinical superiority of high-dose intravenous iron therapy have been demonstrated in patients with chronic renal failure, the effect of this drug on blood transfusion of pre- and post-kidney transplant surgery has not been studied. Therefore, this study aims to verify the effectiveness and stability of the combined administration of intravenous(IV) iron and erythropoiesis-stimulating agents(ESA) before and after KT for patients who perform KT for end-stage kidney disease(ESKD). The investigators will analyze hemoglobin, transferrin saturation, ferritin changes, and transfusion requirements according to the combined administration of IV iron and ESA before and after surgery of kidney transplant patients. Also, the investigators evaluate whether a treatment combining IV iron and ESA will be possible as an alternative blood transfusion treatment and its effect on the clinical prognosis of KT recipients. In particular, the effect on the function of the graft kidney, immunological outcomes-DSA, antibody-mediated rejection, and survival rate will be analyzed. Also, the investigators will analyze the change in expression of hepcidin and oxidative stress markers before and after kidney transplantation and the mechanism of expression according to the combined administration of IV iron and ESA. This study is a multicenter(including 3 centers), open-label, prospective, and randomized clinical trial. 302 patients undergoing living-donor KT for ESKD are randomly assigned in a 1:1 ratio to an experimental group actively using IV iron and ESA, and a control group receiving conventional anemia treatment for 42 months from the time of IRB approval. Participants selected for the experimental group will be given a total of 1000 mg of IV Monofer(iron isomaltoside); each 200 mg dose on 28, 21, and 7 days before kidney transplantation, on the day of surgery, and 7 days after surgery. In the case of ESA, it is freely used according to the criteria up to 7 days before transplantation and subcutaneously injected with 120 mcg of Mircera(methoxy polyethylene glycol-epoetin beta) between 7 days before surgery and a day before surgery. In the control group, IV Monofer is administered only 28 days before surgery according to the set criteria. Mircera is also freely used in the control group according to the criteria up to 7 days before KT but not used between 7 days before surgery and a day before surgery.

Conditions

Kidney Failure, Chronic

Outcome Measures

Primary Outcomes (1)

• Comparison of the number of blood transfusions according to the combination of intravenous iron therapy and EPO agent on perioperative period

  Comparison of the number of blood transfusions(packed RBC transfusion) according to the combination of intravenous iron therapy and EPO agent on perioperative period

  From 1 month before operation to 1 year after operation (28 days before operation, 1st day, 10th day, 1month, 12month after operation)

Secondary Outcomes (6)

• comparison of changes in anemia parameters(ferritin in ng/mL)

  From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)

• comparison of changes in anemia parameters(TSAT in %)

  From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)

• comparison of changes in anemia parameters(EPO level in mU/mL)

  From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)

• comparison of changes in hepcidin expression level in pg/mL

  From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)

• comparison of changes in oxidative stress marker

  From 1 month before operation to 1 year after operation(28 days before operation, 1st day, 10th day, 1month, 12month after operation)

Study Arms (2)

Experimental

EXPERIMENTAL

Drug: Monofer (experimental)

control

OTHER

Follow the criteria for investigational product

Drug: control group

Interventions

Monofer (experimental) DRUG

Monofer 200mg : OP-28day, OP-21day, OP-7day, OP day, POD #7 IV injection, Mircera 120mcg SQ : OP-7 day\~OP-1day

Experimental

control group DRUG

Ferritin\<100, TSAT\<20 : Monofer 200mg IV, twice/ Ferritin 100\~200, TSAT\<20 : Monofer 200mg IV, once / Ferritin 201\~500, TSAT\<20 : Monofer 100mg IV, once / Not administer in any other case

control

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• living donor transplantation (age\>19)
• Ferritin\<700㎍/L, TSAT\<40%

You may not qualify if:

• CDC(+), FXM(+)
• Active infection
• Hematologic malignancy, monoclonal gammaglobulin Dz, Hematologic Dz induced anemia
• Receiving treatment of malignant tumor
• HIV (+)
• ALT, AST \> 3 times upper limit of normal

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Kyu ha huh

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kyu ha huh

CONTACT

82-2-2228-2111; khhuh@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: February 9, 2023
• Study Start: February 1, 2023
• Primary Completion: May 1, 2026
• Study Completion: June 1, 2026
• Last Updated: February 9, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)