Iron Isomaltoside Compared With Iron Sucrosein Peritoneal Dialysis Patients

A Randomized Open-label Trial Cross-over Trial of Iron Isomaltoside 1000 (Monofer®) Compared With Iron Sucrose (Venofer®) in Peritoneal Dialysis Patients

1. To compare patient-reported satisfaction, efficacy and short-term safety profile of Monofer® in a single bolus dose with Venofer® in split doses in the treatment of absolute or functional iron deficiency anemia in patients on PD.
2. To compare patient symptomatology on fatigue after treatment of Monofer® compared with Venofer® .

Study Overview

• Status: Terminated
• Conditions: Iron Deficiency Anemia Treatment
• Intervention / Treatment: Drug: Iron Isomaltoside; Drug: Iron sucrose

Detailed Description

Anemia is commonly present in patients with end-stage renal failure (ESRF) due to insufficient endogenous erythropoietin production, absolute and functional iron deficiency. With the introduction of recombinant human erythropoietin (rHuEPO) and the accessibility of rHuEPO to dialysis patients in the Hospital Authority Drug Formulary, blood transfusion requirement for the treatment of renal related anemia has been much reduced. However, iron store must also be adequately maintained for effective erythropoiesis. The latest KDIGO guideline for anemia in chronic kidney disease recommends iron therapy either in oral or intravenous form if TSAT is ≤30% and ferritin is ≤500µg/L. Oral iron supplement is the most convenient, but it is less effective compared to intravenous forms, especially in the treatment of functional iron deficiency, and has unfavorable patient tolerability and gastro-intestinal side-effect profiles. Iron sucrose (Venofer®) is the most widely used intravenous iron preparation with good safety profile. An initial course of intravenous iron (e.g. Venofer® 200mg weekly for 5 weeks) is commonly given to iron-deplete patients before consideration of maintenance iron therapy. The absence of a vascular access and the need to return to hospital facilities for regular intravenous infusions made intravenous forms less preferred by patients on peritoneal dialysis (PD). Isomaltoside 1000 (Monofer®) consists of iron with a tighter binding to its carbohydrate moiety with less free iron to cause immunologic reactions, and thus allowing for a larger single-dose administration. This may facilitate better acceptance of intravenous iron by patients on PD. The current literature on the efficacy and safety profile of Monofer® in the treatment of renal-related anemia focus mainly on patients on hemodialysis and patients with non-dialysis dependent chronic kidney disease. There is also a lack of information on patient-reported satisfaction on the use of Monofer®. The objective of the current study is to investigate patient-reported satisfaction, efficacy and short-term safety profile of a single bolus of Monofer® compared to Venofer® in the treatment of both absolute and functional iron deficiency anemia in patients on PD. In the second part of the study, patients with recurrent iron deficiency will be crossed-over to receive treatment of the alternative arm. Similar to the first part of the study, patient-reported satisfaction and treatment efficacy will be compared following the same study protocol.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Tung Wah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hemoglobin (Hb) level between 8-12g/dL for the previous 4 weeks prior to screening
• TSAT ≤30% and ferritin ≤500µg/L
• Receiving a stable dose of rHuEPO therapy for the previous 4 weeks prior to screening
• Not on intravenous iron therapy for the previous 4 weeks prior to screening
• Minimum weekly total Kt/V of 1.7
• Able to give informed consent

Exclusion Criteria:

• No evidence of active blood loss or hemolysis
• Untreated Vitamin B12 or folate deficiency
• History of multiple allergies
• Iron overload
• Active acute or chronic infections
• Blood transfusion within the previous 12 weeks
• Uncontrolled malignancy
• Severe hyperparathyroidism (PTH >90 pmol/L)
• Thalassemia or hematological diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Monofer; Iron Isomaltoside as a single intravenous dose 1000mg over 60 minutes	Drug: Iron Isomaltoside; Iron Isomaltoside 1000 (Monofer®) consists of iron with a tighter binding to its carbohydrate moiety with less free iron; Other Names: Monofer; Drug: Iron sucrose; the currently most widely used intravenous iron preparation with good safety profile; Other Names: Monofer
ACTIVE_COMPARATOR: Venofer; Iron Sucrose 200mg weekly intravenous infusions over 2 hours for 5 weeks	Drug: Iron Isomaltoside; Iron Isomaltoside 1000 (Monofer®) consists of iron with a tighter binding to its carbohydrate moiety with less free iron; Other Names: Monofer; Drug: Iron sucrose; the currently most widely used intravenous iron preparation with good safety profile; Other Names: Monofer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported treatment satisfaction with Monofer® versus Venofer®	Patient-reported satisfaction is measured using three questions assessing the view of patients on the medication treatment on the 3 aspects namely effectiveness, convenience and side-effects on a 5-point Likert scale (5 is the maximum score while 1 is the minimum score) and a question on the overall satisfaction of patients with the medication treatment on a numeric rating scale (0 score indicate extremely dissatisfied up to 10, which indicates extremely satisfied). The 4 subscores will be analysed individually.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin level	Hemoglobin level	12 weeks
iron profile	Serum iron, ferritin, total iron binding capacity, transferrin saturation	12 weeks
average weekly dose of rHuEPO	average weekly dose of rHuEPO	12 weeks
patients' subjective assessment of fatigue	Visual Analogue Fatigue Scale - where patients indicate on a horizontal line measuring 100mm (where 0 mm indicates no fatigue and 100 mm point indicates very severe fagitue). The length of the patient's mark from 0mm is measured and is taken as the fatigue score	12 weeks
health-related quality of life	Kidney Disease Quality of Life Short Form Version 1.3. It consists of 36 questions addressing quality of life. Scores of these 36 questions are calculated according to the author's manual and subsequently analysed as one final total score. The higher the score, the better the quality of life.	12 weeks
the incidence of treatment-related adverse events of Monofer	the number of participants with treatment-related adverse events	12 weeks
patients' subjective assessment of fatigue	SF-36 Vitality Scale. Patients were asked in the you during the past 4 weeks how the amount of energy they feel by using 4 questions on the frequency of such feelings a 6-point scale (1 indicates all of the time up to 6 which indicates none of the time). The total score of the 4 questions are averaged for analysis with the lowest score indicating more severe fatigue and the highest score indicating the least fatigue.	12 weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Maggie Ming Yee Mok, MBBS FHKAM, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2019
• Primary Completion (ACTUAL): March 30, 2021
• Study Completion (ACTUAL): March 30, 2021

Study Registration Dates

• First Submitted: May 31, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (ACTUAL): August 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 6, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Physiological Effects of Drugs; Trace Elements; Micronutrients; Hematinics; Iron isomaltoside 1000; Iron; Ferric Oxide, Saccharated; Ferric Compounds
• Other Study ID Numbers: 1.7

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participant data is kept confidential and is only open to investigators and co-investigators of the study

Drug and device information, study documents

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