Use of a Bimodal Solution for Peritoneal Dialysis

Randomized Controlled Trial of Bimodal Solution for Peritoneal Dialysis: 24-Hour UF Efficiency Using Bimodal PD Solutions During the Long Dwell

Peritoneal dialysis (PD) is the method of renal replacement therapy used by close to 200,000 end stage renal disease patients worldwide to help replace the functions that are no longer performed by their kidneys. An important advantage of PD is it offers an alternative to hemodialysis that can be safely performed by patients in their own homes. In PD, the peritoneal membrane that lines the abdomen acts as a dialyzer that allows the transfer of solutes and water between the membrane capillaries and a dialysis solution that is infused into the peritoneal cavity. PD dialysis solutions typically require high concentrations of glucose to adequately perform these functions. Over time the continued exposure of the peritoneal membrane to high concentrations of glucose can permanently damage the membrane. Icodextrin is a polyglucose molecule that has been developed for use in PD solutions that does not harm the peritoneal membrane. However, its use can lead to inadequate fluid removal. Recent research has focused on finding a PD solution, or combination of solutions, that will maximize the removal of toxic substances and metabolites while maintaining regulation of fluid and electrolyte balance in the body. A bimodal solution that combines glucose and icodextrin has been shown in observational studies to be effective and safe. The investigators propose a randomized, controlled, blinded study that will determine the effectiveness and safety of this bimodal fluid in a Canadian PD population. The investigators hypothesize that the use of the bimodal solution during the long (day) dwell will lead to an improvement in 24 hour ultrafiltration efficiency as compared to usual care using icodextrin for the long dwell.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: bimodal solution; Drug: icodextrin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre, South Street Hospital, Peritoneal Dialysis Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be able to provide informed consent
2. Age greater than 18 years
3. Be stable Automated Peritoneal Dialysis (APD) patients for at least 6 weeks

4. Be APD patients who;

   1. Can be managed with an icodextrin long dwell AND
   2. Will use 4.25% and/or a 2.5% solution for at least one exchange overnight in at least 5 out of 7 days
5. Have residual urine volume <800 ml/24 hours
6. Long dwell must be or patient must tolerate at least an 8-10 hr long dwell.

Exclusion Criteria:

1. Scheduled Transplant in the next 1 year
2. Life expectancy < 3 mo (estimated by physician)
3. Participating in other trial that could influence outcome of this trial
4. Known icodextrin allergy
5. Currently using non-Baxter PD solutions
6. Systolic blood pressure < 90 mm Hg on more than three occasions during a seven day period, despite discontinuation of non-essential anti-hypertensives

Supplementary Exclusion Criteria (post Run-in phase):

1) Unsuccessfully completed 1 week run-in phase. Defined as:

1. Not using bimodal solution on 7 consecutive days during the run-in
2. Not tolerating the increased UF anticipated with the bimodal solution. Tolerating defined as:

i) Blood pressure drop below 90/50 on more than three occasions during a seven day period that cannot be corrected by reducing anti-hypertensives or other simple measures ii) Intolerable feeling of fullness with the bimodal solution iii) Allergic reaction (although all patients have already been exposed to icodextrin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bimodal solution; 200 mls of 30% glucose in sterile water is added by the patient to the usual icodextrin day dwell, to create the bimodal solution intraperitoneally	Drug: bimodal solution; 200 mL of 30% glucose infused into the abdomen by the patient each morning for 6 weeks, added to the daytime dwell of approximately 2000 mL icodextrin that has been infused by the cycler
Active Comparator: icodextrin; 200 mls of icodextrin is added by the patient to the usual icodextrin day dwell	Drug: icodextrin; 200 mL of icodextrin infused into the abdomen by the patient each morning for 6 weeks, added to the daytime dwell of approximately 2000 mL icodextrin that has been infused by the cycler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
net ultrafiltration efficiency in mL/g	Ultrafiltration Efficiency (UFE): UFE is defined as the amount of 24 hour net Ultrafiltration (UF) obtained for every gram of carbohydrate absorbed from the dialysis solution.; 24-hour net ultrafiltration (in mL) is recorded automatically by the Automated Peritoneal Dialysis (APD) cycler.; Carbohydrate absorption is determined by calculating the difference (in grams) between the amount of glucose (measured by lab analysis) in the 24 hr peritoneal effluent, and the amount of glucose in the patient's dialysis prescription.; UFE will be calculated in mL/g (ie a divided by b)	Calculated at baseline and at the end of the 6 week intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour absolute total carbohydrate absorption	This will include both glucose and icodextrin absorption.	Calculated at baseline and at the end of the 6 week intervention period
24-hour urine volume		Calculated at baseline and at the end of the 6 week intervention period
24-hour net sodium removal (in both peritoneal effluent and urine)		Calculated at baseline and at the end of the 6 week intervention period
Volume measures as calculated by bioimpedance analysis		Calculated at baseline and at the end of the 6 week intervention period
Weight	Used as an indicator of fluid retention	Calculated at baseline and at the end of the 6 week intervention period
Mean and pulse arterial pressure		Calculated at baseline and at the end of the 6 week intervention period
Number of anti-hypertensive agents		Calculated at baseline and at the end of the 6 week intervention period
Renal (urine) solute clearance (Sodium, Urea, Creatinine)		Calculated at baseline and at the end of the 6 week intervention period
Peritoneal effluent solute clearance (Sodium, Urea, Creatinine)		Calculated at baseline and at the end of the 6 week intervention period

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Arsh K Jain, MD, London Health Sciences Centre, Dept of Medicine, Victoria Campus, London Ontario

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2010
• Primary Completion (Actual): February 28, 2015
• Study Completion (Actual): February 28, 2015

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: November 16, 2010
• First Posted (Estimate): November 17, 2010

Study Record Updates

• Last Update Posted (Actual): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: peritoneal dialysis; dialysis solutions; renal replacement therapy; bimodal solution; glucose sparing therapy
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Pharmaceutical Solutions; Dialysis Solutions; Icodextrin
• Other Study ID Numbers: R-10-460; 17193 (Other Identifier: Research Ethics Board)