CAPD Versus APD in Nondiabetic Peritoneal Dialysis Patients

Study Overview
=================
Brief Summary
-----------------
Background: Continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are two important PD modalities. To date, only three small sample randomized control trials(RCTs) comparing CAPD and APD have been conducted but yield inconsistent results. Objective: Investigators plan to initiate a multicenter, prospective, randomized cross-over study to compare the quality of life and dialysis adequacy in non-diabetic PD patients. Hypothesis: Patients' quality of life and dialysis adequacy on APD is no worse than on CAPD. Methods: This study plans to recruit 268 non-diabetic patients on maintenance peritoneal dialysis. Patients will randomly be assigned into groups A and B in a 1:1 ratio: group A receives APD from week 1 to 12 and changes to CAPD from week 13 to 24; group B receives CAPD from week 1 to 12 and changes to APD from week 13 to 24. Outcomes were evaluated at week 12 and week 24.

Detailed Description
-----------------
This multicenter, randomized, open-label, crossover trial plans to recruit non-diabetic peritoneal dialysis patients by trained investigators according to the inclusion and exclusion criteria. At the beginning of the recruitment visit, each participant is asked to provide written informed consent in compliance with the Declaration of Helsinki and the requirements of the Independent Ethics Committee, after a careful explanation of the purpose and the procedures of the trial. Instructions for manual fluid exchange and automated peritoneal dialysis machines will be provided for each eligible patient, and they will be randomly assigned (1:1) to receive 12-week treatment in group A (APD-CCPD) and group B (CAPD), followed by a subsequent switch to the other modality. Safety assessments and routine visits were performed every 4 weeks thereafter, and efficacy assessments were performed at week 12 and week 24. For the primary efficacy endpoint (the difference of Kt/V compared with baseline 3 months after treatment), 172 patients could provide 80% power to detect an absolute difference of 0.27 (10% of the mean) with a common SD of 0.46 (30% of the mean) at one-sided a=0.025. For another endpoint (the quality of life), previous studies have shown that the mean of a physical composite summary(PCS) score or a mental composite summary (MCS) score in the American population is about 50 points (SD=10), and a 2-point change in PCS or MCS is considered to be clinically significant. In this non-inferiority study, 196 patients could provide 80% power to detect an absolute difference of 4 points in mean change of PCS/MCS between groups at one-sided a=0.025. Considering the 10% rate of loss to follow-up, the sample size of each group was finally determined to be 108 cases.

Official Title
-----------------
The Effectiveness of CAPD Versus APD in Nondiabetic Peritoneal Dialysis Patients: A Multi-center, Randomized, Crossover Study

Conditions
-----------------
Peritoneal Dialysis

Intervention / Treatment
-----------------
* Procedure: Group A and Group B


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 to 75 years; Maintenance peritoneal dialysis for ≥ 1 month; Weekly total CrCL ≥ 45 liters/week/1.73m2 body surface area; Total weekly Kt/Vurea ≥ 1.7. Exclusion Criteria: Patients with diabetes mellitus; Maintained peritoneal dialysis solution with a glucose concentration >2.5%; Combined with acute events of cardiovascular disease(CVD), cardiac function ≥ New York Heart Association (NYHA) class III; Episodes of peritonitis in the past 1 month; Abdominal surgery other than PD catheter insertion in the past 3 months; Planned kidney transplant in the last 6 months; Active hepatitis, cirrhosis, psychiatric disease, malignancy, pregnancy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Non-diabetic patients on maintenance peritoneal dialysis will be randomly assigned into groups A and B in a 1:1 ratio: group A receives APD from week 1 to 12 and changes to CAPD from week 13 to 24; group B receives CAPD from week 1 to 12 and changes to APD from week 13 to 24. Outcomes were evaluated at week 12 and week 24.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Automated Peritoneal Dialysis (APD)<br>In APD, a mechanical device is employed to assist in the delivery and drainage of dialysate. Continuous Cycling Peritoneal Dialysis (CCPD)means patients receive four automated exchanges of 2 liters of dialysate each over 10 hours a night, with 2 liters left in the peritoneal cavity during the daytime. The overall dialysate volume is 10 liters. | Procedure: Group A and Group B<br>* Group A: Participants receive APD for 12 weeks then switch to CAPD for another 12 weeks; Group B: Participants receive CAPD for 12 weeks and switch to APD for another 12 weeks.<br>|
| Active Comparator: Continuous Ambulatory Peritoneal Dialysis (CAPD)<br>CAPD involves the manual instillation of 2 liters(L) of dialysis fluid into the peritoneal cavity, four times a day. This typically means three short dwells during the daytime and a long dwell overnight. The total volume of dialysate is 8 liters. | Procedure: Group A and Group B<br>* Group A: Participants receive APD for 12 weeks then switch to CAPD for another 12 weeks; Group B: Participants receive CAPD for 12 weeks and switch to APD for another 12 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of standardized total urea clearance index(Kt/V) | Kt/V = Kd×T/V. Kd is peritoneal urea nitrogen removal rate. T is the time (unit: min). V represents the urea distribution volume(weight×0.58)] | up to 24 weeks | 
| Assessment of health-related quality of Life | The abbreviated version of the Kidney Disease Quality Of Life Short Form 36 (KDQOL-36) is a self-reported questionnaire for assessing health-related quality of life (HRQOL). The scores of KDQOL-36 at the 12th week will be compared to that of the 24th week. The KDQOL-36 contains 5 subscales with 36 items: the Physical Component Summary (PCS), Mental Component Summary (MCS), Burden of Kidney Disease (BKD), Symptoms and Problems of Kidney Disease (SPKD), and Effects of Kidney Disease (EKD). The raw scores are transformed linearly to a range of 0(minimum value) to 100(maximum value), with higher scores indicating better health-related quality of life. | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social Function | Social Disability Screening Schedule(SDSS) score at the 12th week will be compared to that of the 24th week. The SDSS scales were originally developed by the Disability Assessment Schedule of World Health Organization. The SDSS scale is composed of 10 items, which is used to assess social function. Each item is scored from 0 = healthy or very minor defects to 2 = severe defects. The minimum value is 0 and the maximum value is 20. A higher score means more severe impairment of a social function. | up to 24 weeks | 
| Episodes of Peritonitis | PD patients presenting with cloudy effluent should be presumed to have peritonitis, which should be confirmed by obtaining effluent cell count, differential and culture. | The 24th week | 
| Residual Renal Function | Residual renal function should preferably be measured by 24h urine collection and calculation of the residual glomerular filtration rate, as represented by the average 24h urinary urea and creatinine clearances. | up to 24 weeks | 
| 24-hour ambulatory blood pressure(ABP) | Participants wear a 24-hour ambulatory BP(blood pressure) monitor (conventional cuff-based oscillometric device) on their upper arm programmed to measure BP every 20 minutes during awake hours and every 30 minutes during asleep hours. Ambulatory BP data are extracted and processed by a single trained investigator. Investigators applied the American Heart Association's guidelines and defined daytime as 10 AM(ante meridiem) to 8 PM(post meridiem) and nighttime as midnight to 6 AM. At least 20 daytime and 7 nighttime readings were required for a participant's data to be included in the analysis. Investigators derive average daytime and nighttime BP, BP dip ratio (average nighttime BP divided by average daytime BP), and nighttime BP dipping (absolute difference between nighttime BP and daytime BP). BP dip ratios allow for the comparison of BP dipping in relation to daytime BP, thus providing a more comprehensive assessment of ambulatory BP patterns than absolute dipping alone. | up to 24 weeks | 
| Standardized total creatinine clearance (CrCL) | The weekly total CrCL was calculated as the arithmetic sum of weekly peritoneal CrCL and GFR.The weekly peritoneal CrCL (pCrCL,L) was calculated as follows: [(dialysate Cr/serum Cr) × drainage volume] × 7.Peritoneal CrCL was measured using the 24h dialysate collection. The weekly glomerular filtration rate (GFR, L) was calculated as follows: [(renal urea CL + renal CrCL) × 12 ] × 7. The weekly GFR was added to the weekly pCrCL to obtain the weekly total CrCL, which was normalized to a BSA (Body Surface Area) of 1.73 m2 . | up to 24 weeks | 
| Daily average net ultrafiltration volume | Net ultrafiltration volume was calculated as the volume of the drained dialysate(L) - the volume of infused dialysis fluid(L). The volume of the drained dialysate was measured by weighing the bag and subtracting the weight of the empty bag from the full bag. | up to 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dialysis Adequacy, Quality of Life, Continuous Ambulatory Peritoneal Dialysis, Automated Peritoneal Dialysis