Cancer, Constipation
Conditions
Keywords
Constipation, Opioids, Cancer, Polyethylene glycol, Sennosides, Opioid Therapy
Brief summary
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
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.
Interventions
DRUGPEG then Senna
Stepped bowel protocol with PEG for 3 weeks followed by senna for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).
DRUGSenna then PEG
Stepped bowel protocol with senna for 3 weeks followed by PEG for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).
Sponsors
British Columbia Cancer Agency
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind using a dummy alternate treatment.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patient (18 years and above) with diagnosis of cancer. 2. Patient requires treatment or prevention of constipation. 3. Patient is able to communicate effectively with staff. 4. Expected prognosis more than 12 weeks. 5. On or starting opioid therapy
Exclusion criteria
1. Patient unable to take oral medication. 2. Allergy or previous intolerance to PEG or sennosides. 3. Lactose intolerant. 4. Contraindication to PEG or sennosides. 5. Known or suspected bowel obstruction or ileus. 6. Colostomy or ileostomy. 7. Inflammatory bowel disease. 8. Hospitalisation expected within the study period. 9. Patient unable to complete the study diary in English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bowel Performance Scale (BPS) | Last 18 days of each 21 day study period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Preference | end of study (6 weeks) | 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). |
| Time (in Days) to Attain an Ideal BPS Score of Goal | 3 weeks (ascertained at the end of period 1) | 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. |
| Incidence of Cramps | Last 18 days of each 21 day study period | The patients were asked to indicate any experience of cramps while on study treatment |
| Rectal Measures | Last 18 days of each 21 day study period | The patients were asked to indicate any experience of rectal bleeding or rectal pain while on study treatment |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PEG Then Senna PEG in stepped bowel protocol
PEG then Senna: Stepped bowel protocol with PEG for 3 weeks followed by senna for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder). | 37 |
| Senna Then PEG Stepped bowel protocol with Senna then PEG
Senna then PEG: Stepped bowel protocol with senna for 3 weeks followed by PEG for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder). | 33 |
| Total | 70 |
Baseline characteristics
| Characteristic | PEG Then Senna | Senna Then PEG | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 11 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 22 Participants | 42 Participants |
| Age, Continuous | 72.8 years | 59.2 years | 66 years |
| Diagnosis Bladder | 1 Participants | 0 Participants | 1 Participants |
| Diagnosis Brain | 1 Participants | 0 Participants | 1 Participants |
| Diagnosis Breast | 9 Participants | 4 Participants | 13 Participants |
| Diagnosis GI | 3 Participants | 3 Participants | 6 Participants |
| Diagnosis Haematological | 3 Participants | 5 Participants | 8 Participants |
| Diagnosis Kidney | 1 Participants | 0 Participants | 1 Participants |
| Diagnosis Lung | 4 Participants | 6 Participants | 10 Participants |
| Diagnosis Other | 12 Participants | 12 Participants | 24 Participants |
| Diagnosis Prostate | 3 Participants | 3 Participants | 6 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 23 Participants | 15 Participants | 38 Participants |
| Sex: Female, Male Male | 14 Participants | 18 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 1 / 70 |
| other Total, other adverse events | 6 / 70 | 7 / 70 |
| serious Total, serious adverse events | 0 / 70 | 0 / 70 |
Outcome results
Primary
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.
Time frame: Last 18 days of each 21 day study period
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Polyethylene Glycol (PEG) | Bowel Performance Scale (BPS) | Period 1 | 0.659 Ratio |
| Polyethylene Glycol (PEG) | Bowel Performance Scale (BPS) | Period 2 | 0.641 Ratio |
| Sennosides | Bowel Performance Scale (BPS) | Period 1 | 0.534 Ratio |
| Sennosides | Bowel Performance Scale (BPS) | Period 2 | 0.636 Ratio |
Secondary
Incidence of Cramps
The patients were asked to indicate any experience of cramps while on study treatment
Time frame: Last 18 days of each 21 day study period
Population: Patients who reported incidence of cramps at least once.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polyethylene Glycol (PEG) | Incidence of Cramps | 27 Participants |
| Sennosides | Incidence of Cramps | 25 Participants |
Secondary
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).
Time frame: end of study (6 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polyethylene Glycol (PEG) | Patient Preference | 13 Participants |
| Sennosides | Patient Preference | 13 Participants |
| No Preference | Patient Preference | 2 Participants |
Secondary
Rectal Measures
The patients were asked to indicate any experience of rectal bleeding or rectal pain while on study treatment
Time frame: Last 18 days of each 21 day study period
Population: Patients who reported incidence of rectal pain or rectal bleeding at least once.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Polyethylene Glycol (PEG) | Rectal Measures | Rectal Bleeding | 7 Participants |
| Polyethylene Glycol (PEG) | Rectal Measures | Rectal Pain | 10 Participants |
| Sennosides | Rectal Measures | Rectal Bleeding | 6 Participants |
| Sennosides | Rectal Measures | Rectal Pain | 9 Participants |
Secondary
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.
Time frame: 3 weeks (ascertained at the end of period 1)
Population: Patients with a minimum of 7 days of treatment in the first period were included in the modeling.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polyethylene Glycol (PEG) | Time (in Days) to Attain an Ideal BPS Score of Goal | 6 Days |
| Sennosides | Time (in Days) to Attain an Ideal BPS Score of Goal | 8 Days |