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

Study Overview
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Brief Summary
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The DIDo study is an open-label, randomised, multicentre study with 2 parallel groups in incident CAPD patients aged of 65 at minimum : One group in which patients will receive 2 bags of icodextrin/day and 1 bag of glucose One group in which patients will receive 1 bag of icodextrin/day and 2 bags of glucose.

Detailed Description
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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.

Official Title
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Efficacy and Safety of a Double Icodextrin Dose in Elderly Incident CAPD Patients on Incremental Peritoneal Dialysis Therapy: the DIDo Study

Conditions
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Renal Insufficiency

Intervention / Treatment
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* Drug: Icodextrin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 icodextrin bags/day<br>2 icodextrin bags + 1 glucose per day | Drug: Icodextrin<br> <br> * Other names: Extraneal;|
| Active Comparator: 1 icodextrin bag/day<br>1 icodextrin bag + 2 glucose bags per day | Drug: Icodextrin<br> <br> * Other names: Extraneal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients stopping 3 bags / day | 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. | During the treatment phase of 18 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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icodextrin, double dose, elderly incident CAPD patients, DIDo study