Constipation
Conditions
Keywords
constipation, opioid, rehabilitation, post-operative, orthopedic
Brief summary
Patients requiring opioids for post-operative pain control following elective orthopedic procedures which has resulted in constipation symptoms, and who are in inpatient rehabilitation will be randomized to two different treatment arms: lubiprostone or senna. Baseline scores regarding constipation and a quality of life bowel questionnaire will be compared the day following 6 days of treatment intervention.
Detailed description
The purpose of this study is to assess the efficacy of Lubiprostone (Amitiza) compared to standard care for the treatment of constipation in orthopedic patients receiving opioids for pain control during inpatient rehabilitation. Lubiprostone (Amitiza®) is a locally acting chloride channel activator that increases intestinal fluid, and thus increases intestinal motility. It has been approved for chronic constipation, but not in the setting of opioid-induced constipation. Senna is a stimulant laxative that increases propulsive peristaltic activity of the colon through local effects on the mucosa. Subjects will be compared using from the Patient Assessment of Constipation (PAC) which has previously been found to be a valid and reliable way to measure constipation symptoms and clinical course. (Frank, Kleinman et al. 1999) as well as with other measures of bowel-related symptoms and functional outcomes.
Interventions
DRUGLubiprostone
24 µg po BID given with meals for 6 days
DRUGSenna
2 tabs daily for 6 days
Sponsors
Takeda Pharmaceuticals North America, Inc.
Shirley Ryan AbilityLab
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult, 18 years old or greater. 2. The patient is able to provide informed consent. 3. Anticipated duration of hospitalization of at least 7 days. 4. Woman of childbearing potential must have a negative serum pregnancy test at enrollment. Exclusions for testing include two years or greater postmenopausal, hysterectomy or tubal ligation. 5. Use of opioid for post-op analgesia following orthopedic surgical procedures as defined as IV, IM, transdermal or PO opioid received within the prior 24 hours of hospitalization for pain control, and expectation that an opioid will be continued for pain control. * Medication may be administered on a PRN (as needed) basis or scheduled basis * One or greater doses has been received within the 24 hours prior to enrollment as determined by medication administration recorded from the acute care facility or RIC MAR. 6. At least one associated symptom of constipation at the time of admission, such as, but not limited to: * Lumpy or Hard stools * Feeling of incomplete evacuation of bowels * Abdominal cramping or pain * Straining with movement of bowels or painful bowel movement effort * Need for manual assistance to have a bowel movement
Exclusion criteria
1. Known allergy or sensitivity to the study medications 2. Females who are pregnant 3. Diarrhea on the day of admission 4. Diagnosis of Clostridium difficile infection during the current hospitalization 5. Pre-existing medical condition or surgical procedure, which is known to commonly lead to bowel dysfunction such as, but not limited to: * Crohn's disease * Ulcerative colitis * Multiple sclerosis * Cerebral palsy * Spinal Cord Injury * Colectomy * Malabsorption Syndrome * Irritable Bowel Syndrome * Abdominopelvic neoplasm (gastric, colon cancer) * Severe liver disease * Colonic or ileo-colonic resections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient Assessment of Constipation (PAC) - Symptoms (Sym) | Baseline and Day 7, after treatment completed (6 days of treatment) | Patient Assessment of Constipation (PAC) - Change in this measure was assessed. The PAC has previously been found to be a valid and reliable way to measure constipation symptoms and clinical course. The PAC has two components. The symptom (SYM) component is composed of 12 items with score range 0-4 with lower scores indicating improvement. Scores within the two domains were separately averaged. The PAC-SYM questionnaire has shown good concurrent and clinical validity for opioid-induced constipation in a number of pain populations and has demonstrative responsiveness to treatment. There are three symptom domains within the PAC-SYM: Abdominal symptoms (4 items), rectal symptoms (3 items) and stool symptoms (5 items). |
| Change in Patient Assessment of Constipation - Quality of Life | Baseline and day 7 | The second component of the PAC is the quality of life (QOL) component.The quality of life (QOL) component consists of five items that are rated on a 0-4 scale with higher scores indicating better QOL. Scores within the domains are averaged. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the inpatient population of an academic freestanding rehabilitation hospital following admission for impairments related to an orthopedic surgery.The study was approved by the local institutional review board and all subjects provided written informed consent.
Pre-assignment details
72 patients were recruited. There were eight who did not meet inclusion and/or exclusion criteria following consent and screening visit. Reasons for exclusion were: history of Crohn's disease (1 person), history of irritable bowel disease (1 person), diarrhea on baseline visit day (1 person), or no associated bowel symptom (5 persons).
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone Lubiprostone24 µg po BID for 6 days with placebo senna tab | 32 |
| Senna Senna 2 tabs daily for 6 days with placebo lubiprostone tabs | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Discharged early from rehab | 4 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Senna | Lubiprostone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 25 Participants | 23 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Age Continuous | 72.2 years STANDARD_DEVIATION 10.5 | 70.9 years STANDARD_DEVIATION 11.8 | 71.6 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment United States | 32 participants | 32 participants | 64 participants |
| Sex: Female, Male Female | 17 Participants | 22 Participants | 39 Participants |
| Sex: Female, Male Male | 15 Participants | 10 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 31 | 11 / 29 |
| serious Total, serious adverse events | 1 / 31 | 1 / 29 |
Outcome results
Primary
Change in Patient Assessment of Constipation (PAC) - Symptoms (Sym)
Patient Assessment of Constipation (PAC) - Change in this measure was assessed. The PAC has previously been found to be a valid and reliable way to measure constipation symptoms and clinical course. The PAC has two components. The symptom (SYM) component is composed of 12 items with score range 0-4 with lower scores indicating improvement. Scores within the two domains were separately averaged. The PAC-SYM questionnaire has shown good concurrent and clinical validity for opioid-induced constipation in a number of pain populations and has demonstrative responsiveness to treatment. There are three symptom domains within the PAC-SYM: Abdominal symptoms (4 items), rectal symptoms (3 items) and stool symptoms (5 items).
Time frame: Baseline and Day 7, after treatment completed (6 days of treatment)
Population: All subjects randomized and who had baseline and endpoint data were included in the intention to treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Change in Patient Assessment of Constipation (PAC) - Symptoms (Sym) | -0.22 units on a scale | Standard Deviation 0.57 |
| Senna | Change in Patient Assessment of Constipation (PAC) - Symptoms (Sym) | -0.29 units on a scale | Standard Deviation 0.58 |
Comparison: Primary outcome measures chosen were between group comparisons for change on Constipation Symptom Questionnaire ratings at exit from the study. The PAC-SYM is a symptom scale where higher numbers indicate more symptoms. Change from baseline to Day 7 was calculated and larger negative differences indicated greater improvement in constipation symptoms. The PAC-QOL is a quality of life scale where higher numbers indicate better quality of life. Change from baseline to 7 days was calculated.p-value: <0.05independent sample t test
Primary
Change in Patient Assessment of Constipation - Quality of Life
The second component of the PAC is the quality of life (QOL) component.The quality of life (QOL) component consists of five items that are rated on a 0-4 scale with higher scores indicating better QOL. Scores within the domains are averaged.
Time frame: Baseline and day 7
Population: intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Change in Patient Assessment of Constipation - Quality of Life | 0.99 units on a scale | Standard Deviation 0.78 |
| Senna | Change in Patient Assessment of Constipation - Quality of Life | .42 units on a scale | Standard Deviation 0.84 |