Iron Isomaltoside for the Treatment of Anemia in Peritoneal Dialysis Patients

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Iron isomaltoside
  Intravenous infusion of 1000mg iron isomaltoside as a single dose for over 15min. Iron isomaltoside 1000mg was diluted in 100ml of 0.9% saline.
• Препарат Ferrous succinate
  Patients received ferrous succinate treatment orally given as 200mg twice a day for 8 weeks.

Первичные конечные точки

• Changes in hemoglobin concentration from baseline to week 8 [Срок оценки: Screening period，Day 1，Week 1，Week 4，Week 8]

Вторичные конечные точки (5)

• Changes in hemoglobin concentration from baseline to week 4 [Срок оценки: Screening period，Day 1，Week 1，Week 4]
• Iron metabolism indices and reticulocyte count at week 8 [Срок оценки: Screening period，Day 1，Week 1，Week 4，Week 8]
• Iron metabolism indices and reticulocyte count at week 4 [Срок оценки: Screening period，Day 1，Week 1，Week 4]
• Compound cardiovascular adverse events at Week 8 [Срок оценки: Through study completion, an average of 1 year]
• Adverse Events [Срок оценки: Through study completion, an average of 1 year]

Критерии участия

Критерии включения

• Males or females who are ≥ 18 years and on PD treatment for ≥90 days, body weight≥50Kg
• Hemoglobin(Hb）≤110 g/L at screening phase
• Serum ferritin(SF）≤200 μg/L or transferrin saturation(TSAT）≤20% at screening phase
• No oral or intravenous iron use within 4 weeks prior to screening.
• 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
• Stable doses of erythropoiesis-stimulating agents (ESA) with a change of dose ≤20% during the past 4 weeks.
• Willing to participate and signed the informed consent form

Критерии исключения

• 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)
• History of disturbances in iron utilisation.(eg. hemochromatosis and hemosiderosis）
• 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
• Histories of serious allergies to iron
• Obvious liver dysfunction：ALT>3×ULN and/or AST>3×ULN，or total bilirubin>1.5×ULN
• Active acute or chronic infection(clinically diagnosed)
• Uncontrolled secondary hyperparathyroidism：PTH or iPTH>9×ULN；
• History of malignancy within 5 years
• Acute coronary syndrome, strokes (except for lacunar cerebral infarction), serious thromboembolism (eg. DVT or PE) within 6 months before the screening period
• 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
• Pregnant or during lactation period or not willing to get contraception
• Planning to receive renal transplantation within 2 months
• Accepted blood transfusion within 3 months.
• Serum ferritin，SF>500 μg/L
• Planning to recieve the treatment as operations, chemotherapies or radiotherapies etc. during the research period
• Other situations not suitable for inclusion decided by researchers. Rescreening is allowed if it failed in the first time of screening.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Kalra PA, Bhandari S, Saxena S, Agarwal D, Wirtz G, Kletzmayr J, Thomsen LL, Coyne DW. A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney disease patients with anaemia. Nephrol Dial Transplant. 2016 Apr;31(4):646-55. doi: 10.1093/ndt/gfv293. Epub 2015 Aug 6. PMID 26250435
• Bhandari S, Kalra PA, Kothari J, Ambuhl PM, Christensen JH, Essaian AM, Thomsen LL, Macdougall IC, Coyne DW. A randomized, open-label trial of iron isomaltoside 1000 (Monofer(R)) compared with iron sucrose (Venofer(R)) as maintenance therapy in haemodialysis patients. Nephrol Dial Transplant. 2015 Sep;30(9):1577-89. doi: 10.1093/ndt/gfv096. Epub 2015 Apr 28. PMID 25925701
• Bhandari S, Kalra PA, Berkowitz M, Belo D, Thomsen LL, Wolf M. Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial. Nephrol Dial Transplant. 2021 Jan 1;36(1):111-120. doi: 10.1093/ndt/gfaa011. PMID 32049331
• Futterer S, Andrusenko I, Kolb U, Hofmeister W, Langguth P. Structural characterization of iron oxide/hydroxide nanoparticles in nine different parenteral drugs for the treatment of iron deficiency anaemia by electron diffraction (ED) and X-ray powder diffraction (XRPD). J Pharm Biomed Anal. 2013 Dec;86:151-60. doi: 10.1016/j.jpba.2013.08.005. Epub 2013 Aug 14. PMID 23998966
• Jahn MR, Andreasen HB, Futterer S, Nawroth T, Schunemann V, Kolb U, Hofmeister W, Munoz M, Bock K, Meldal M, Langguth P. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm. 2011 Aug;78(3):480-91. doi: 10.1016/j.ejpb.2011.03.016. Epub 2011 Mar 23. PMID 21439379
• Auerbach M, Henry D, DeLoughery TG. Intravenous ferric derisomaltose for the treatment of iron deficiency anemia. Am J Hematol. 2021 Jun 1;96(6):727-734. doi: 10.1002/ajh.26124. Epub 2021 Feb 26. PMID 33580972
• Auerbach M, Gafter-Gvili A, Macdougall IC. Intravenous iron: a framework for changing the management of iron deficiency. Lancet Haematol. 2020 Apr;7(4):e342-e350. doi: 10.1016/S2352-3026(19)30264-9. PMID 32220343
• Bazeley JW, Wish JB. Recent and Emerging Therapies for Iron Deficiency in Anemia of CKD: A Review. Am J Kidney Dis. 2022 Jun;79(6):868-876. doi: 10.1053/j.ajkd.2021.09.017. Epub 2021 Nov 7. PMID 34758368

Идентификаторы

NCT: NCT06830941 · Iron isomaltoside-PD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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