Iron Isomaltoside for the Treatment of Anemia in Peritoneal Dialysis Patients

Efficacy and Safety of Iron Isomaltoside in the Treatment of Peritoneal Dialysis Patients with Renal Related Anemia: a Randomized Controlled Trial

This is a prospective multicenter randomized controlled clinical study. The goal of this clinical trial is to learn if intravenous iron isomaltoside injection use is equally effective and safe for the treatment of renal anemia in peritoneal dialysis patients compared with oral ferrous succinate tablets.

The main questions to answer are:

• Changes in hemoglobin concentration from baseline to week 8 after the use of single dose intravenous iron isomaltoside injection in peritoneal dialysis patients with renal anemia.
• If intravenous iron isomaltoside injection use is equally effective and safe for the treatment of renal anemia in peritoneal dialysis patients compared with oral ferrous succinate tablets.

Participants will:

• be randomized 1:1 to two groups, either Iron isomaltoside Group (Group A, experimental group) or Ferrous succinate Group (Group B, control group).
• Patients in Iron isomaltoside Group will receive a single dose of intravenous iron isomaltoside injection, the dose of which is set at 1000 mg. Patients in Ferrous succinate Group will receive ferrous succinate treatment orally given as 200mg twice a day for 8 weeks (containing iron element 7840mg in total).
• Patients will be followed up for 8 weeks.

This is a prospective multicenter randomized controlled clinical study. The purpose of this study is to evaluate the efficacy and safety of single dose intravenous iron isomaltoside comparing with daily oral ferrous succinate in the treatment of renal anemia among patients on peritoneal dialysis.

A total of 124 patients will be enrolled. The primary endpoint is hemoglobin change from baseline to week 8, the secondary endpoint is hemoglobin change from baseline to week 4. Other secondary endpoints include the results of iron metabolism, reticulocytes, composite cardiovascular events, laboratory and safety parameters. The expected result is that intravenous iron isomaltoside is equally effective and safe for the treatment of renal anemia in peritoneal dialysis patients compared with oral ferrous succinate tablets.

Inclusion Criteria:

1. Males or females who are ≥ 18 years and on PD treatment for ≥90 days, body weight≥50Kg
2. Hemoglobin(Hb）≤110 g/L at screening phase
3. Serum ferritin(SF）≤200 μg/L or transferrin saturation(TSAT）≤20% at screening phase
4. No oral or intravenous iron use within 4 weeks prior to screening.
5. No hypoxia-inducible factor prolyl hydroxylase inhibitor（HIF-PHI）used or other erythropoiesis-stimulating agent（ESA）except for erythropoietin (EPO) used in the past 4 weeks prior to screening
6. Stable doses of erythropoiesis-stimulating agents (ESA) with a change of dose ≤20% during the past 4 weeks.
7. Willing to participate and signed the informed consent form

Exclusion Criteria:

1. Anemia predominantly caused by other diseases rather than renal diseases according to the investigator's judgement. (eg. bleeding, hematological diseases, anemia due to autoimmune diseases)
2. History of disturbances in iron utilisation.(eg. hemochromatosis and hemosiderosis）
3. Anemia due to lack of folate or vitamin B12：folate<6.8nmol/L（3ng/ml）and(or) Vitamin B12<74pmol/L（100pg/ml）at screening phase
4. Histories of serious allergies to iron
5. Obvious liver dysfunction：ALT>3×ULN and/or AST>3×ULN，or total bilirubin>1.5×ULN
6. Active acute or chronic infection(clinically diagnosed)
7. Uncontrolled secondary hyperparathyroidism：PTH or iPTH>9×ULN；
8. History of malignancy within 5 years
9. Acute coronary syndrome, strokes (except for lacunar cerebral infarction), serious thromboembolism (eg. DVT or PE) within 6 months before the screening period
10. NYHA grade III or IV of congestive heart failure or severe arrythmia(including ventricular tachycardia, ventricular fibrillation, AV-block III etc.) within 6 months before screening
11. Pregnant or during lactation period or not willing to get contraception
12. Planning to receive renal transplantation within 2 months
13. Accepted blood transfusion within 3 months.
14. Serum ferritin，SF>500 μg/L
15. Planning to recieve the treatment as operations, chemotherapies or radiotherapies etc. during the research period
16. Other situations not suitable for inclusion decided by researchers. Rescreening is allowed if it failed in the first time of screening.