Colonoscopy
Conditions
Keywords
Routine screening colonoscopy, Colonoscopy Preparation, Amitiza, GoLYTELY, Pegylated Electrolytes, Preparation Solution, Colonoscopy Solution
Brief summary
The primary objective is to compare the effectiveness and tolerance of the medication named lubiprostone plus a large volume liquid laxative versus placebo which is a look alike medication that has no effect such as a sugar pill plus a large volume liquid laxative as a bowel cleaning preparation for colonoscopy to see the colon better during the colonoscopy to identify abnormal growths such as polyps or colon cancer. Colonoscopy is considered the best way to screen for colon cancer screening because you can visualize the colon directly and remove or biopsy abnormal growths. The limiting step in the procedure is the quality of the colon preparation prior to the procedure. Many patients do not tolerate large volumes of liquid used to prepare the colon. The purpose of the study is to improve the quality of the prep by adding a pill laxative medication before starting the large volume laxative to better see the colon. The other aim of the study is to try to reduce the amount of of liquid laxative the patient has to drink by giving a pill laxative before starting the liquid laxative.
Detailed description
The study is a double blind placebo controlled study of lubiprostone in 4 doses vs look alike placebo in 4 doses before bowel preparation for outpatient screening, surveillance and diagnostic colonoscopy. Patients with severe underlying medical conditions were excluded. Patients with inflammatory bowel disease, frequent bowel movements and colonic resection were also excluded. Patients were randomized to one of two groups. The study was double blinded. The first group took lubiprostone 24 micrograms and the second group took look alike placebo in 4 divided doses right before starting the bowel prep with the last dose upon starting polyethylene glycol-electrolyte solution the evening before the colonoscopy. All study patients were educated and instructed to observe for clear stool, which was defined as watery consistency without any solid fecal material or dark liquid stools before stopping the liquid bowel prep. Patients were instructed to return the unused PEG solution on the day of colonoscopy. After completing the preparation but before colonoscopy, patients were also required to fill a questionnaire to assess the tolerability of tablets and solution. This was measured on a 1-5 rating Likert scale (1) Easy, 2) Tolerable, 3) Slightly Difficult, 4) Extremely Difficult, and 5)Unable to Finish and was based on the patient's ability to swallow the liquid and each of 4 tablets. In addition, the pres- ence of symptoms of nausea, vomiting, abdominal pain, chest pain, dizziness, and bloating was evaluated. The primary endpoints was the endoscopist's evaluation of the preparation quality. All colonoscopies were performed by 3 endoscopists (with 85% of the procedures performed by principal investigator of the study, A.L.S.). Endo- scopists evaluated the quality of the colonoscopy prep- aration based on the previously validated Ottawa bowel preparation scale.5 This scale rates 3 sections of colon, rectosigmoid, mid, and right colon, on a 5-point scale (0-4) and a global 3-point rating (0-2) for overall colonic fluid. The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid.The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group.
Interventions
DRUGlubiprostone (Amitiza)
24 mcg administered 4 times over the two days before the colonoscopy. 96 mcg total
DRUGPlacebo
Amitiza Placebo
Sponsors
Takeda Pharmaceuticals North America, Inc.
Henry Ford Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blinding was done to ensure minimum bias. The clinicians attending to the patients were not involved in the randomization process, and all were blinded to the identity of the drug received as the placebo was identical to the active drug in packaging, appearance, and schedule of administration. Separate individuals generated the allocation sequence, enrolled participants, and assigned participants to their groups. The blind was maintained until all decisions regarding data evaluability were made. Only the research assistant who assigned participants to their treatment groups was permitted access to the randomization list, which was maintained in a locked filing cabinet during the trial. The patients were blinded to their medication status.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subject is at least 18 years old * Subject is in good health * Subject is undergoing a screening, surveillance or diagnostic colonoscopy * Subject has a spontaneous bowel movement at least every 48 hours
Exclusion criteria
* Subject has renal insufficiency demonstrated by serum creatinine \> 1.4mg/dL * Subject has Type 1 diabetes * Subject has past or present diagnosis of Congestive Heart Failure * Subject has past or present diagnosis of inflammatory bowel disease * Subject had previous colon resection * Subject has a preexisting electrolyte abnormality * Subject has more than 3 spontaneous bowel movements daily
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopist Evaluation of Colon Cleanliness in the Lubiprostone Group vs the Placebo Group | within 12 hours of completing bowel prep | Endoscopists evaluated the quality of the colonoscopy preparation based on Ottawa bowel preparation scale. . The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid. Before using the scale for this trial, the endoscopists participated in a calibration exercise that involved 20 patients to ensure that they concurred on their interpretation of the scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | done at the time of colonoscopy | After completing the colonoscopy prep patients were asked to assess tolerability of the prep using a 5 point Likert scale with 1 being easy and 5 being unable to complete the prep |
| Change in Volume of PEG From Beginning of Bowel Prep to That at Completion of the Colonoscopy Preparation in the Two Groups | amount of PEG at start of the study and that measured when the patient presented for their procedure. | Patients in the lubiprostone group and the placebo returned unused PEG after completing the prep for the colonoscopy. This was measured in liters and recorded. |
Countries
United States
Participant flow
Recruitment details
Two hundred patients were planned to enroll in the study; however, the study was discontinued by the sponsor before the enrollment goal was completed because of slow enrollment. Of the 157 patients who volunteered for the study, only 123 patients who actually did the bowel preparation. Patients were recruited from the gastroenterology clinic at the main hospital and at the satellite clinic in the suburbs of Detroit.
Pre-assignment details
Exclusion criteria included serum creatinine greater than 1.4, type I diabetes, CHF, pre-existing electrolyte abnormalities, inflammatory bowel disease, no spontaneous bowel movement every 48 hours, more than 3 bowel movements daily and previous colon resection.
Participants by arm
| Arm | Count |
|---|---|
| 2 Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. group 2 ingested 4 tablets of placebo (in divided doses) + 1 gallon of PEG. First dose of placebo was administered 2 nights before colonoscopy and subsequent doses at breakfast, lunch, and dinner on the day before the procedure. Patients were instructed to initiate drinking PEG (immediately after the last dose of lubiprostone) at 6 PM the evening before the colonoscopy and continue drinking the solution until at least 2 bowel movements were clear yellow or green. Patients evaluated the prep on a 1-5 rating Likert scale 1)Easy, to 5) Unable to Finish In addition, the presence of symptoms of nausea, vomiting, abdominal pain, chest pain, dizziness, and bloating were also recorded.All colonoscopies were performed by 3 endoscopists (with 85% of the procedures performed by principal investigator of the study, A.L.S.). Endoscopists evaluated the quality of the colonoscopy preparation based on the Ottawa bowel preparation scale. This scale rates 3 sections of colon, rectosigmoid, mid, and right colon, on a 5-point scale (0-4) and a global 3-point rating (0-2) for overall colonic fluid. The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid. All patients were contacted by telephone the day after the procedure to determine if they were experiencing any adverse reactions. | 66 |
| 1 Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. First dose of lubiprostone was administered 2 nights before colonoscopy and subsequent doses at breakfast, lunch, and dinner on the day before the procedure. Patients were instructed to initiate drinking PEG (immediately after the last dose of lubiprostone) at 6 PM the evening before the colonoscopy and continued drinking the solution until at least 2 bowel movements were clear yellow or green. After completing the preparation but before colonoscopy, patients were also required to fill a questionnaire to assess the tolerability of tablets and solution. This was measured on a 1-5 rating Likert scale 1) Easy, up to 5) Unable to Finish. In addition, the presence of symptoms of nausea, vomiting, abdominal pain, chest pain, dizziness, and bloating was also noted. All colonoscopies were performed by 3 endoscopists (with 85% of the procedures performed by principal investigator of the study, A.L.S.). Endoscopists evaluated the quality of the colonoscopy preparation based on the Ottawa bowel preparation scale. This scale rates 3 sections of colon, rectosigmoid, mid, and right colon, on a 5-point scale (0-4) and a global 3-point rating (0-2) for overall colonic fluid. The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid. All patients were contacted by telephone the day after the procedure to determine if they were experiencing any adverse reactions. | 57 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 19 | 15 |
| Overall Study | unclear if patient took all the medication. | 1 | 0 |
Baseline characteristics
| Characteristic | 1 Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Total | 2 Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. |
|---|---|---|---|
| Age, Continuous age | 55.8 years STANDARD_DEVIATION 9.4 | 56.0 years STANDARD_DEVIATION 9.2 | 56.1 years STANDARD_DEVIATION 9.1 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 57 participants | 123 participants | 66 participants |
| Sex: Female, Male Female | 35 Participants | 76 Participants | 41 Participants |
| Sex: Female, Male Male | 22 Participants | 47 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 66 |
| other Total, other adverse events | 41 / 57 | 46 / 66 |
| serious Total, serious adverse events | 0 / 57 | 0 / 66 |
Outcome results
Primary
Endoscopist Evaluation of Colon Cleanliness in the Lubiprostone Group vs the Placebo Group
Endoscopists evaluated the quality of the colonoscopy preparation based on Ottawa bowel preparation scale. . The total score ranges from 0-14; score of 0 being perfect and score of 14 indicating solid stool in each colon segment and lot of fluid. Before using the scale for this trial, the endoscopists participated in a calibration exercise that involved 20 patients to ensure that they concurred on their interpretation of the scale.
Time frame: within 12 hours of completing bowel prep
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Endoscopist Evaluation of Colon Cleanliness in the Lubiprostone Group vs the Placebo Group | 1.38 score on a scale | Standard Deviation 0.49 |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Endoscopist Evaluation of Colon Cleanliness in the Lubiprostone Group vs the Placebo Group | 1.24 score on a scale | Standard Deviation 0.59 |
Comparison: Based on the assumption that 70% of patients using PEG plus placebo (group 2) will have good results, by allocating 100 cases in each group, we will have 84% power to detect a difference of 18% or more in the effectiveness of PEG plus lubiprostone combination (group 1) (eg, 70% in group 2 vs. 88% in group 1) at the alpha level of significancelevel of significance.p-value: 0.05t-test, 2 sided
Secondary
Change in Volume of PEG From Beginning of Bowel Prep to That at Completion of the Colonoscopy Preparation in the Two Groups
Patients in the lubiprostone group and the placebo returned unused PEG after completing the prep for the colonoscopy. This was measured in liters and recorded.
Time frame: amount of PEG at start of the study and that measured when the patient presented for their procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Change in Volume of PEG From Beginning of Bowel Prep to That at Completion of the Colonoscopy Preparation in the Two Groups | 0.79 liters | Standard Deviation 0.97 |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Change in Volume of PEG From Beginning of Bowel Prep to That at Completion of the Colonoscopy Preparation in the Two Groups | 1.36 liters | Standard Deviation 1.04 |
p-value: <0.05ANCOVA
Secondary
Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group
After completing the colonoscopy prep patients were asked to assess tolerability of the prep using a 5 point Likert scale with 1 being easy and 5 being unable to complete the prep
Time frame: done at the time of colonoscopy
Population: Patients completed the drug or placebo with PEG and completed a questionnaire on the day of of the colonoscopy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | Tolerable | 15 participants |
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | extremely difficult | 6 participants |
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | slightly difficult | 18 participants |
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | unable to finish | 7 participants |
| Look Alike Placebo in 4 Divided Doses Plus PEG and Electrolytes. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | easy | 6 participants |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | unable to finish | 6 participants |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | easy | 4 participants |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | Tolerable | 14 participants |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | slightly difficult | 25 participants |
| Patient Received Both Lubiprostone in 4 Divided Doses and Golytely. | Tolerability of the Colon Cleansing Group in the Lubiprostone Group vs the Placebo Group | extremely difficult | 15 participants |
p-value: <0.052 sided Cochran-Armitage trend test