Polyethylene Glycol (PEG) Versus Sennosides Study in Opioid-Induced Constipation in Cancer Patients

Study Overview
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Brief Summary
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This is a study to compare the efficacy and tolerability of two laxatives for treatment of opioid-induced constipation in adult outpatients with cancer treated at the British Columbia Cancer Pain and Symptom Management/Palliative Care clinics. Each participating patient will be randomly assigned to one of two treatment groups.

Detailed Description
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One group will be started on a bowel protocol of escalating doses of sennosides, plus a dummy polyethylene glycol (lactose), and the other will receive dummy sennosides capsules (lactose) plus polyethylene glycol, with the same dosing protocol. After three weeks of one active treatment the patients will switch to the alternate active product and dummy preparation. The total duration for the study will be 6 weeks for each patient.

Official Title
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A Randomized, Double Blind, Double-dummy, 2-treatment, 2-period Crossover Comparison of Sennosides and Polyethylene Glycol in Treatment of Opioid-induced Constipation in Outpatients With Cancer

Conditions
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Constipation, Cancer

Intervention / Treatment
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* Drug: PEG then Senna
* Drug: Senna then PEG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient (18 years and above) with diagnosis of cancer. Patient requires treatment or prevention of constipation. Patient is able to communicate effectively with staff. Expected prognosis more than 12 weeks. On or starting opioid therapy Exclusion Criteria: Patient unable to take oral medication. Allergy or previous intolerance to PEG or sennosides. Lactose intolerant. Contraindication to PEG or sennosides. Known or suspected bowel obstruction or ileus. Colostomy or ileostomy. Inflammatory bowel disease. Hospitalisation expected within the study period. Patient unable to complete the study diary in English.

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The primary outcome will be treated as a binomial outcome, expressed as the number of successful trials out of a pre-defined number of trials n = 18. Given this, the primary outcome will be analysed via a generalized mixed effects model. The model will include: (i) fixed effects for treatment, treatment period and their interaction, (ii) fixed effects for the baseline characteristics and (iii) a random patient effect. Including the latter effect in the model will help capture the within-patient correlation among the values of the primary outcome collected in Period I and Period II for the same patient. All statistical analyses will be conducted using the open-source statistical software package R.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG then Senna<br>PEG in stepped bowel protocol | Drug: PEG then Senna<br>* Stepped bowel protocol with PEG for 3 weeks followed by senna for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).<br>* Other names: Lax-a-Day;|
| Experimental: Senna then PEG<br>Stepped bowel protocol with Senna then PEG | Drug: Senna then PEG<br>* Stepped bowel protocol with senna for 3 weeks followed by PEG for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).<br>* Other names: senokot;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel Performance Scale (BPS) | Mean values of Number of Days with Satisfactory Bowel Movements Per Days of Treatment across time by treatment, derived from the mixed effects Poisson regression model. If the BPS rating on a day was -1, 0 or +1, the patient's bowel movement on that day was deemed to be satisfactory. | Last 18 days of each 21 day study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Preference | The patients will be asked to state which treatment period they prefer. Only assessed using patients who completed both arms of the study (n=28). | end of study (6 weeks) | 
| Time (in Days) to Attain an Ideal BPS Score of Goal | Proportion of patients in the study population estimated to reach a BPS at goal in the first period as a function of the time (in days) from day 1, presuming they were followed for 21 days and contributed a BPS score on each of those days. Constipation was graded using the Victoria Bowel Performance Scale (BPS), a nine-point scale from -4 (constipation) to +4 (diarrhea) which has been validated for use in patients receiving palliative care. | 3 weeks (ascertained at the end of period 1) | 
| Incidence of Cramps | The patients were asked to indicate any experience of cramps while on study treatment | Last 18 days of each 21 day study period | 
| Rectal Measures | The patients were asked to indicate any experience of rectal bleeding or rectal pain while on study treatment | Last 18 days of each 21 day study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioids, Constipation, Cancer, Polyethylene glycol, Sennosides, Opioid Therapy