Peritoneal Dialysis Pilot Study: Evaluating Polyethylene Glycol (PEG) for Constipation

Study Overview
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Brief Summary
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Constipation is a common condition, which occurs one in four Canadians. Maintaining regular bowel movements is imperative because constipation can affect the quality of PD dialysate flow and result in an unwanted effect on the dialysis adequacy. There is limited data on how to best manage constipation in the peritoneal dialysis population. Polyethylene glycol (PEG) is an osmotic laxative that is becoming popular for prevention and treatment of constipation across Canada. Although some PD programs in Canada have already converted to PEG for management of constipation, more research in this population would help guide practice. For now, the current PD bowel regimen at the Nova Scotia Health Authority (NSHA) includes daily preventative therapy using a stimulant laxative, senna, along with an osmotic laxative, lactulose, for acute constipation. The investigators will review all patients in the NSHA PD program who have regular or recent laxative use for participation in this study. Patients included in this study will be randomly assigned to the Current Bowel Protocol or the PEG Bowel Protocol for 8 weeks. The goal is to determine if the PEG Bowel Protocol is as effective and safe for the prevention of constipation as the Current Bowel Protocol used in the PD Program. The investigators will use bowel function diaries and patient surveys to determine efficacy and safety outcomes.

Detailed Description
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Constipation is a common condition, which impacts one in four Canadians Maintaining regular bowel movements is important in the peritoneal dialysis (PD) population because constipation can negatively impact the quality of dialysate flow and can result in impaired dialysis adequacy. Unfortunately, treating constipation is challenging in PD patients because of the diet and fluid restrictions required in this population, as well as the need for constipating calcium based phosphate binders. Constipation treatment can be administered orally or rectally. Although patients often prefer oral therapy, there are occasions when rectal therapy is preferred (ie. rectal suppositories and enemas). Oral laxatives include bulk, osmotic, stimulant, and lubricants. In the Nova Scotia (NS) PD Program, patients are counseled to maintain a type 3-4 stool on the Bristol Stool Chart (BSC). An ideal stool is a type 4, which appears like a sausage or snake and is smooth and soft in consistency. To maintain a type 3-4 stool, current therapy includes senna 8.6-17.2 g twice daily with the addition of lactulose 30-60 mL twice daily, as needed. Rescue therapy in the Current Bowel Protocol is lactulose 30-60 mL every hour until bowel movement. There is limited evidence to guide the ideal bowel regimen in PD patients. Reasons to consider PEG therapy include the evidence promoting PEG in the general population with constipation, the positive outcomes found in a small population of PD patients (Mimidis 2005), as well as positive feedback from other provinces who currently recommend PEG in PD patients. The investigators postulate the PEG protocol would be as effective and safe as the Current Bowel Protocol, and thus will evaluate PEG in the PD population, the investigators will conduct a prospective, interventional, randomized, open label, pilot study. All patients with recent laxative use will be approached for inclusion. Patients will be randomly assigned to the Current Bowel Protocol (senna/lactulose) or the PEG Bowel Protocol (PEG/lactulose) for 8 weeks. The primary objective is to compare the efficacy of the PEG Bowel Protocol in preventing constipation to the Current Bowel Protocol. We will review the safety of the regimens by monitoring for adverse events from all laxatives and explore the impact of constipation in patients who experience PD treatment failure.

Official Title
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An Evaluation of the Efficacy and Safety of a Polyethylene Glycol (PEG) Based Bowel Protocol for the Management of Constipation in Peritoneal Dialysis Patients: A Pilot Study

Conditions
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Constipation, Peritoneal Dialysis Complication

Intervention / Treatment
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* Drug: Current Bowel Protocol (senna/lactulose)
* Drug: PEG Bowel Protocol (PEG/lactulose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients in the peritoneal dialysis program in Nova Scotia who are currently taking laxatives. Exclusion Criteria: Allergy or intolerance to any of the study laxatives (PEG, senna, lactulose); cognitive impairment or inability to document symptoms; known or suspected gastrointestinal obstruction or ileus; known or planned pregnancy; no laxative use in the last 3 months.
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
Interventional Model Description: Patients will be randomized to received the Current Bowel Protocol or the PEG Bowel Protocol
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Current Bowel Protocol<br>Patients will receive the Current Bowel Protocol with senna. Lactulose will be used for rescue therapy. | Drug: Current Bowel Protocol (senna/lactulose)<br>* Stimulant and Osmotic Laxatives.<br>* Other names: NPN: 00026158;|
| Active Comparator: PEG Bowel Protocol<br>Patients will receive the Protocol with Polyethylene Glycol 3350. Lactulose will be used for rescue therapy. | Drug: PEG Bowel Protocol (PEG/lactulose)<br>* Osmotic Laxatives.<br>* Other names: DIN: 02412268;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of constipation treatment success | Successful treatment of constipation will be defined based on a modified ROME criteria developed by Dipalma 2007: relief of constipation for more than 50% of the weeks in the study. | 8 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with laxative related adverse effects. | Compare the occurrence of side effects during the study period. | 8 weeks. | 
| Mean change from baseline on the PAC-SYM questionnaire | Measure of the impact of constipation disease severity. PAC-SYM = Patient Assessment of Constipation Symptoms (Frank 1999 and Bove 2012) | 8 weeks. | 
| Mean change from baseline on the PAC-QOL questionnaire | Measure the impact of constipation on quality of life. PAC-QOL = Patient Assessment of Constipation Quality of Life (Marquis 2005 and Bove 2012) | 8 weeks | 
| Incidence of peritoneal dialysis treatment failure requiring intervention | Interventions include antibiotics for peritonitis, catheter re-positioning. | 8 weeks |