E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with chronic renal failure who are starting a Continuous Ambulatory Peritoneal Dialysis (CAPD) as first line dialyse. |
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E.1.1.1 | Medical condition in easily understood language |
Chronic renal insuffciency |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007184 |
E.1.2 | Term | CAPD |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the superiority and safety of using 2, as compared to 1, icodextrin bags / day, in a cohort of elderly incident CAPD patients using incremental PD (3 bags / day), with the aim of prolonging the period of time for which incremental PD can be used. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to demonstrate the efficacy of the double icodextrin dose on various clinical and biological determinants as well as on safety issues.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Run-in period
- Incident CAPD patients who require incremental PD and in whom a 2L dialysate can be safely instilled,
- Creatinine clearance <20ml/min
- Age ≥ 65 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).
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E.4 | Principal 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 the signature of the informed consent form,
- History of drug or alcohol abuse within 3 months prior to the signature of the informed consent form.
Treatment period
- Severe symptomatic arterial hypotension at the end of 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, psycho-social reasons).
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E.5 End points |
E.5.1 | Primary end point(s) |
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 period,
- Transfer of the patient to another dialysis method (haemodialysis [HD], automated peritoneal dialysis [APD], CAPD with > 3 bags / day) for any reason,
- Death of the patient.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be evaluated at 9 months (visit 5) |
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E.5.2 | Secondary end point(s) |
The secondary endpoints will demonstrate the efficacy of the double icodextrin dose on various clinical and biological determinants as well as on safety issues:
- Metabolic control: glycosylated haemoglobin (HbA1c) and lipid concentration total, high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, cholesterol),
- Blood pressure control, evaluated by the number of anti-hypertensive agents and daily furosemide dose, and measured at the end of each study visit,
- Nutritional aspect: serum albumin and prealbumin concentrations based on the changes in percentage at various time points compared to baseline (V2),
- Inflammatory profile: C-reactive protein (CRP) concentrations,
- Left ventricular mass calculated following ECG,
- Quality of life according to the kidney disease quality of life (KDQoL) evaluation,
- Residual renal function evaluated by calculated glomerular filtration rate (GFR, creatinine + urea clearances/2),
- Peritoneal membrane permeability assessed by the peritoneal equilibration test (PET),
- Number of hospitalisations and length (in days) of hospitalisation,
- Adverse events (AEs), treatment-emergent AEs and serious adverse events (SAEs),
- Serum sodium concentration and icodextrin metabolites concentration,
- Relevant clinical problems related to serum sodium concentration and to icodextrin metabolites accumulation,
- Incidence of skin rashes,
- Incidence of sterile peritonitis. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary variables will be summarised and compared between groups at each time point:
- V2 (D0), V4 (M6), V6 (M12) and V7 (M18) for all variables except left ventricular mass which is not measured at V4 and V6,
- V3 (M3) for all except quality of life, peritoneal membrane permeability (by PET) and left ventricular mass,
- V5 (M9) for all except quality of life and peritoneal membrane permeability (by PET).
In addition, change and percent change from baseline (V2) to each time point will be described and compared between groups for the following variables:
- HbA1c and lipids concentrations (total, HDL, LDL, triglycerides, cholesterol),
- Serum albumin and prealbumin concentrations,
- CRP concentrations.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Collections of biological samples to perform further researches aimed to improve the knowledge on the peritoneal membrane :
- Whole blood samples for genetic research
- urine, serum and dialysis effluent samples
- peritoneal biopsies
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study will occur 12 months after the last patient last visit because a follow-up contact is planned after the study completion by the patient. This contact will be done 12 months after the end of the study to know when the peritoneal dialysis was finaly stopped by the patient and the current modality of dialysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |