Comparing High and Low Dose Iron Treatments for People on Peritoneal Dialysis: The PALaDIN Study

Official title

Proactive High Dose Versus Low-dose Reactive Intravenous or Oral Iron in People on Peritoneal Dialysis (PALaDIN) - an Open-label, Feasibility Randomised Study

Overview

Chronic kidney disease affects a significant portion of the UK population, with approximately 3.5 million adults diagnosed. At its most severe stage, end-stage kidney disease, individuals require frequent dialysis treatment. One form of dialysis, known as peritoneal dialysis, involves introducing and removing fluid from the abdominal cavity to help filter out toxins from the body. The kidneys are involved in various hormonal processes, including those responsible for producing red blood cells, making anaemia a common consequence of kidney failure. When designing a clinical trial to evaluate the effectiveness of any treatment, it is essential to determine the number of suitable and willing participants, as well as those who can complete all required tests and measurements. Identifying the most appropriate measurement to assess the impact of intravenous iron (iron injected directly into veins) is crucial to ensure that any observed changes are meaningful to people with CKD and their carers. To address these considerations, the investigators will conduct a pilot feasibility trial. In this trial, individuals with kidney disease undergoing peritoneal dialysis will be randomly assigned to receive either high-dose or low-dose intravenous iron, or oral iron therapy. Over twelve months, the investigators will monitor their anaemia response, symptoms of kidney disease, quality of life, physical performance (such as the ability to walk for six minutes), and cognitive function. Additionally, the investigators will assess the impact of each intervention on the frequency of blood transfusions, whether those on oral iron require intravenous iron, and any changes in the dosage of erythropoietin-stimulating agents (drugs that increase blood production).

Interventions

• Drug Monofer (iron isomaltoside 1000)
  Intravenous iron infusion, administered in this study up to every 3 months. Dosage determined by haemoglobin and weight.
• Drug Ferrous Sulfate
  Oral iron tablet taken once daily for duration of study.

Primary outcome measures

• Eligibility to consent rate (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Recruitment rate (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Participant retention to 12 month follow-up (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Completion of clinical outcomes at follow-up and patterns of missing data for the study measures (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Completion of patient symptom questionnaires throughout the study (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Treatment adherence (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Treatment fidelty (%) [Time frame: From enrollment to the end of treatment at 12 months]
• Treatment acceptability (%) [Time frame: From enrollment to the end of treatment at 12 months]

Secondary outcome measures (12)

• Adverse and serious adverse events [Time frame: From enrollment to the end of treatment at 12 months]
• Mortality and Major Adverse Cardiovascular Events (MACE) [Time frame: From enrollment to the end of treatment at 12 months]
• Hospital Admissions [Time frame: From enrollment to the end of treatment at 12 months]
• Drug Reactions [Time frame: From enrollment to the end of treatment at 12 months]
• Infections and Peritoneal Dialysis Peritonitis [Time frame: From enrollment to the end of treatment at 12 months]
• Quality of life (KDQoL-SF) [Time frame: From enrollment to the end of treatment at 12 months]
• Symptom burden (IPOS-Renal, PROMIS Global Health Instrument) [Time frame: From enrollment to the end of treatment at 12 months]
• Physical Function (6-Minute Walk Test) [Time frame: From enrollment to the end of treatment at 12 months]
• Cognitive Function (MoCA) [Time frame: From enrollment to the end of treatment at 12 months]
• Residual Renal Function (Creatinine Clearance) [Time frame: From enrollment to the end of treatment at 12 months]
• Restless Legs Syndrome (IRLSSG) [Time frame: From enrollment to the end of treatment at 12 months]
• >10g/L Rise in Haemoglobin (Hb) [Time frame: From enrollment to the end of treatment at 12 months]

Eligibility criteria

Inclusion criteria

• Males and females aged ≥18 years.
• Able to give informed consent
• Serum ferritin <700ug/L
• Transferrin saturation level <40%
• No intravenous iron for last 4 weeks before randomisation (patients may be pre-identified and included after 4-week washout period)
• Received maintenance peritoneal dialysis therapy for at least 4 weeks
• Expected to remain on peritoneal dialysis therapy for duration of study

Exclusion criteria

• Inadequate dialysis deemed by responsible clinician
• Probability of need for transfusion within 1 week of enrolment
• On or received a HIF-PHI in the past 4 weeks
• Anticipated major surgery that the responsible clinician feels will impact response to treatment
• Haemochromatosis / haemosiderosis or ALT >x3 normal
• Are deemed to be most suited to best-supportive or end-of-life care at time of screening
• Women of childbearing potential not using effective means of contraception
• Have been involved in another medicinal study (CTIMP) within past 4 weeks
• Known allergy or adverse reaction to oral or intravenous iron preparations
• CRP >50, TSATs >40%, SF >700 at time of recruitment
• Active infection, HIV, active Hep B or C
• Are unable or unwilling to consent to or complete the study procedures

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• Hull University Teaching Hospitals NHS Trust — Hull

Identifiers

NCT: NCT06884280 · R4171

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗