Efficacy and Safety of a Double Icodextrin Dose in Elderly Incident CAPD Patients on Incremental PD.

The DiDo study evaluates efficacy and safety of a Double Icodextrin Dose in elderly incident CAPD patients on incremental Peritoneal Dialysis therapy.

The objective is to demonstrate the superiority and safety of using 2, as compared to 1, icodextrin bags / day, in a cohort of elderly incident continuous ambulatory peritoneal dialysis (CAPD) patients using incremental peritoneal dialysis (PD) (3 bags / day), with the aim of prolonging the period of time for which incremental PD can be used.

This is a phase IV open-label, randomised, multicentre study with 2 parallel groups, which will take place in up to 30 hospital out-patient clinics un Europe.

It is planned to include 160 patients on the run-in period in order to obtain 100 randomised patients and 90 patients evaluable at the primary endpoint (45 in each group). The duration of patient recruitment is estimated at 1 year but this may be extended until all 160 patients are recruited.

There are 2 periods: a run-in period of 2 months and a treatment period of 18 months.

• Icodextrin (Drug), also known as Extraneal

Primary outcomes

• Proportion of patients stopping 3 bags / day [During the treatment phase of 18 months]: The primary endpoint will be the proportion of patients stopping 3 bags / day for the following reasons: * Use of > 15 % hypertonic glucose dialysate 3.86 % or > 30 % hypertonic glucose dialysate 2.27 % over a 4-week period19-20, * Transfer of the patient to another dialysis method (HD, APD, CAPD with > 3 bags / day) for any reason, * Death of the patient.

Secondary outcomes

• effect on clinical and biological determinants [During 18 months, evaluated on month 3, 6, 9, 12 and 18.]: • Metabolic control: HbA1c and lipid concentration (total, high-density lipoprotein \[HDL\], low-density lipoprotein \[LDL\], triglycerides, cholesterol)
• effect on clinical and biological determinants [During 18 months, evaluated on month 3, 6, 9, 12 and 18.]: • Blood pressure control, evaluated by the number of anti-hypertensive agents and daily furosemide dose, and measured at the end of each study visit
• effect on clinical and biological determinants [During 18 months, evaluated on month 3, 6, 9, 12 and 18.]: • Nutritional aspect: serum albumin and prealbumin concentrations based on the changes in percentage at various time points compared to baseline (V2)
• effect on clinical and biological determinants [During 18 months, evaluated on month 3, 6, 9, 12 and 18.]: • Inflammatory profile: CRP concentrations
• effect on clinical and biological determinants [Month 9 and month 18.]: • Left ventricular mass calculated following echocardiography
• effect on clinical and biological determinants [Month 6, 12 and 18.]: • Quality of life according to KDQoL
• effect on clinical and biological determinants [During 18 months, evaluated on month 3, 6, 9, 12 and 18.]: • Residual renal function evaluated by calculated GFR
• effect on clinical and biological determinants [On month 6, 12 and 18.]: • Peritoneal membrane permeability assessed by the PET
• effect on clinical and biological determinants [During the treatment phase of 18 months.]: • Number of hospitalisations and length (in days) of hospitalisation
• Safety endpoints [Durign the treatment phase of 18 months.]: • Adverse events (AEs), treatment-emergent AEs and serious adverse events (SAEs)
• 6.1.3 Safety endpoints [On month 3, 6, 12 and 18.]: • Serum sodium concentration and icodextrin metabolites concentration
• safety endpoints [During the treatment phase of 18 months.]: • Relevant clinical problems related to serum sodium concentration and to icodextrin metabolites accumulation
• Safety endpoints [During the treatment phase of 18 months.]: • Incidence of skin rashes
• Safety endpoints [During the treatment phase of 18 months.]: • Incidence of sterile peritonitis

Sex: All, ages: 60 Years to any

Inclusion Criteria:

Run-in period

* Incident CAPD patients who require incremental PD and in whom a 1.5L dialysate can be safely instilled,
* Creatinine clearance < 20 ml / min (calculated with the modification of the Diet in renal Disease \[MDRD\] formula),
* Age ≥ 60 years,
* Patients willing and able to give written informed consent and comply with the requirements of the study protocol.

Treatment period

* Patients having successfully completed the run-in period (achieving euvolemia)

Exclusion Criteria:

Run-in period

* Contraindication for CAPD according to local practice,
* Life expectancy < 6 months,
* Known allergy to icodextrin (cloudy dialysate or skin rash),
* Need for amino-acid prescription,
* Treatment with any investigational product within 30 days prior to signature of the informed consent form (ICF)
* History of drug or alcohol abuse within 3 months prior to the signature of the ICF.

Treatment period

* Severe symptomatic arterial hypotension at the end the run-in period in the Investigator's opinion,
* Excessive ultrafiltration (UF) during the run-in period,
* Allergy to icodextrin discovered during the run-in period,
* Impossibility to achieve adequate PD regimen within the run-in period (catheter dysfunction, peritoneal leaks, inadequate compliance, psychosocial reasons)

• Results publication: Morelle J, Lambie M, Oberg CM, Davies S. The Peritoneal Membrane and Its Role in Peritoneal Dialysis. Clin J Am Soc Nephrol. 2024 Feb 1;19(2):244-253. doi: 10.2215/CJN.0000000000000282. Epub 2023 Aug 24. PMID 37616463

• Eric Goffin, Principal investigator, UCL