Abstract
OBJECTIVES:
Despite the importance of adequate bowel cleansing prior to colonoscopy, national societies provide little guidance regarding which bowel preps are best tolerated and most effective; this reflects a lack of comparative effectiveness studies that directly evaluate available preps in a “real-world” setting. To address this gap, we conducted a prospective, naturalistic, commercially unfunded, comparative effectiveness study of currently available bowel preps and measured their impact on bowel cleansing.
METHODS:
We included patients ≥18 years old who presented for an outpatient colonoscopy at a large medical center serving >70 academic and community-based endoscopists who are free to prescribe the bowel prep of their choice. The primary outcome was bowel cleansing quality as measured by the Boston Bowel Preparation Scale (BBPS). The secondary outcome was prep tolerability. We performed regression models with random effects on the outcomes to adjust for confounding.
RESULTS:
There were 4339 colonoscopies performed by 75 endoscopists. Magnesium citrate, Miralax® with Gatorade®, Moviprep®, Osmoprep®, Prepopik®/Clenpiq®, and Suprep® all had significantly higher prep tolerability compared to GoLYTELY® (all p<.05). For bowel cleansing, Suprep® (7.28 ± 1.66; p<.001), Moviprep® (7.11 ± 1.62; p=.004), and Miralax® with Gatorade® (7.09 ± 1.64; p<.001) had higher total BBPS scores vs. GoLYTELY® (6.67 ± 1.87); there were no significant differences among the remaining preps. Split-prep dosing was associated with better cleansing, while men, opioid and tricyclic antidepressent users, diabetics, and cirrhotics had worse cleaning (all p<.05).
CONCLUSIONS:
In this prospective, real-world, comparative effectiveness study of currently available bowel preps, we found that Miralax® with Gatorade®, Moviprep®, and Suprep® were prospectively associated with superior tolerability and bowel cleansing.
INTRODUCTION
While colorectal cancer (CRC) is largely preventable, it remains a major public health issue and is the third most common malignancy in the U.S. in both men and women.(1) The U.S. Preventive Services Task Force recommends that all Americans undergo screening starting at age 50 with one of several supported approaches, including fecal-based tests, computerized tomographic colonography, and flexible sigmoidoscopy.(2) However, colonoscopy remains the gold standard; it is the only test that is both cancer-detecting and cancer-preventing through removal of adenomatous polyps – the CRC precursor.(3–5)
Over 14 million colonoscopies are performed annually in the U.S.(6) Selecting the optimal bowel prep has a major impact on the effectiveness of colonoscopic CRC screening and is a critical process measure along the path towards improved screening outcomes.(7) Although adequate bowel cleaning is essential for a successful colonoscopy, inadequate preparation occurs in up to 25% of procedures (8, 9), leading to impaired visualization, missed polyps, and lower adenoma detection rates (ADR), thereby increasing risk of interval CRC.(10)
As of September 2018, there are more than 10 commercially available bowel preps, with each varying in volume, tolerability, and formulation. Despite the importance of bowel cleansing, national societies provide minimal guidance regarding which preps are best tolerated and most effective, or how best to navigate among the available options.(11, 12) Current guidelines only recommend selection of a prep that accounts for a patient’s medical history, medications, and cleansing adequacy from prior exams.(11, 12) This non-specific recommendation reflects a lack of comparative effectiveness studies that directly evaluate available preps in a “real world” setting. Most of the available data are from randomized controlled trials (RCTs) comparing two or three preps at a time in the context of tightly controlled research protocols that may not accurately reflect real world conditions.(11)
Although the efficacy of the various bowel preps has been well studied in RCTs, clinical effectiveness of these preps in daily clinical practice is largely unstudied. The lack of comparative evidence data creates uncertainty among patients, clinicians, and other stakeholders regarding which bowel preps to use in CRC screening programs. Moreover, without prospective comparative effectiveness data, clinicians may be using preps that appear efficacious in RCTs, but are not equally effective in everyday clinical practice where issues around tolerability intersect with patients’ knowledge, attitudes, and beliefs about CRC screening (13, 14), leading to complexities in administering and achieving effective bowel preps.(8, 9) To address this gap in knowledge, we aimed to conduct a prospective, naturalistic, commercially unfunded, comparative effectiveness study to assess the impact of currently available preps on bowel cleansing quality and tolerability in real world conditions.
METHODS
Study Design, Patients, and Setting
We performed a prospective, naturalistic, comparative effectiveness study at Cedars-Sinai Medical Center, which is a quaternary care hospital and multi-specialty health science center that provides healthcare for the diverse population of Los Angeles, California. Cedars-Sinai is affiliated with over 70 academic and community-based endoscopists who perform greater than 4000 inpatient and outpatient colonoscopies annually at the medical center. These clinicians have individual choice to use any available bowel prep and are not bound by a restrictive formulary.
We enrolled patients, aged ≥18 years old, who presented for an outpatient colonoscopy for any indication between August 4, 2016 to July 31, 2018. All patients were assessed prospectively at the time of colonoscopy using the Boston Bowel Preparation Scale (BBPS), a validated and widely used measure of bowel cleansing. The BBPS score is documented as part of routine clinical care by the procedure nurse rather than any members of the research team (see the Primary Outcome – Bowel Cleansing section below for more details).(15, 16) Individuals with surgically absent colon segments or whose procedure was aborted for reasons unrelated to bowel prep (e.g., technical difficulties, patient instability or intolerance, etc.) were excluded from the study because these scenarios cannot be completely scored using the BBPS. We also excluded those who received a two-day “double” bowel prep. The Cedars-Sinai Medical Center Institutional Review Board approved this study (IRB# Pro41005).
Primary Outcome – Bowel Cleansing
The primary outcome was bowel cleansing using the BBPS.(15, 16) We assessed bowel cleansing in two ways: (i) total BBPS score; and (ii) adequate bowel cleansing, which was defined as a total BBPS score ≥6 with each segment BBPS score ≥2 (right, transverse, and left colon).
For every colonoscopy performed at Cedars-Sinai, the BBPS score for each segment of the colon is assessed and documented in the electronic health record (EHR) by the procedure nurse. The evaluation is performed independently by the nurse, and a survey of the nursing staff revealed that the proceduralists rarely provide input on the BBPS score. Although this process is already part of routine clinical care, research investigators (P.G. and C.V.A.) conducted in-services with the endoscopy nurses about one month prior to (July 14, 2016) and six months (February 23, 2017) after initiation of the study to reinforce correct application of the BBPS during the withdrawal phase and once all cleaning has been completed. During both sessions, the instructors guided the nursing staff through the BBPS Educational Program (vimeo.com/31111826) developed by the Boston University School of Medicine Clinical Outcomes Research Initiative.(15, 16) Moreover, to support continued appropriate use of the BBPS throughout the study as well as to account for staff turnover, the EHR BBPS module was updated prior to initiation of the study to include hover text explaining each BBPS score (15, 16): (i) N/A – surgically absent colon segment or segment not seen for reasons unrelated to bowel prep such as technical difficulties or patient instability or intolerance; (ii) 0 – unprepared colon segment, mucosa not seen due to solid stool; (iii) 1 – portion of mucosa of the colon seen, residual stool; (iv) 2 – minor amount of residual staining, mucosa seen; (v) 3 – entire mucosa of colon segment seen well, no residual staining.
Secondary Outcome – Bowel Prep Tolerability
We assessed for bowel prep tolerability by determining whether the patient completed the bowel prep as prescribed. Prior to each colonoscopy, the pre-procedure nurse asked all patients “How much of the bowel prep did you ingest?” and answer options in the EHR included: (i) all (100%) of the prep; (ii) 75 to 99% of the prep; (iii) <75% of the prep; and (iv) unsure. For the purposes of the study, we dichotomized responses to (i) fully completed prep and (ii) did not fully complete prep.
Covariates – Prescribed Bowel Preps and Dosing
All endoscopists were free to prescribe the prep and dosing of their choice. To determine the prescribed prep, pre-procedure nurses asked all patients “What bowel prep did you take?” The answer options included: (i) GoLYTELY®; (ii) Colyte®; (iii) NuLYTELY®; (iv) Trilyte®; (v) Moviprep®; (vi) Miralax® with Gatorade®; (vii) Suprep®; (viii) Suclear®; (ix) Prepopik®; (x) Osmoprep®; (xi) magnesium citrate; (xii) other; and (xiii) unknown. Bowel prep “face sheets” that included pictures of the packaging of the commonly used preps were located at all pre-procedure bays to assist patients who had difficulty remembering their prescribed prep. We also validated the accuracy of the patients’ self-reported prep by manually examining 100 random charts and found that the prep reported by patients matched the prep documented in their clinic notes in 95% of cases. Dosing information was also collected in the pre-procedure setting, where the nurses asked all patients “Did you ingest all of the bowel prep yesterday OR did you split the bowel prep by ingesting half of it yesterday and finishing the rest of it today?”
Because Colyte®, NuLYTELY®, and Trilyte® were not commonly prescribed, they were consolidated into the GoLYTELY® category as they have similar formulation and volume. Suclear® was similarly grouped with Suprep®. Clenpiq® was approved by the U.S. Food and Drug Administration (FDA) after initiation of the study and was combined with the Prepopik® group. As part of this study, use of adjunctive measures, such as bisacodyl, was not systematically collected in order to reduce the documentation burden on the pre-procedure nurses and to minimize the impact on lab efficiency. Moreover, use of adjunctive agents has not been definitively shown to improve outcomes; a study by Gerard and colleagues comparing Miralax® with Gatorade® with or without bisacodyl found no difference in bowel cleansing between the groups.(17) Of note, interviews with providers at our institution revealed that bisacodyl was often given along with Miralax® with Gatorade®.
Covariates – Patient, Procedure, and Endoscopist Characteristics
We collected data on patient-, procedure-, and provider-level variables with potential to impact bowel prep effectiveness and tolerability. Patient-related factors included demographics (age, gender, race/ethnicity, primary language), body mass index, medication use (opioids, tricyclic antidepressants), and relevant comorbidities (diabetes, cirrhosis). Procedure- and provider-level factors included the primary performing endoscopist, whether another procedure (e.g., upper endoscopy, endoscopic ultrasound, etc.) was performed in addition to the colonoscopy, fellow trainee involvement, and withdrawal time (defined as time cecum reached – time scope was removed).
Statistical Analysis
All statistical analyses were performed in Stata 13.1 (StataCorp LP, College Station, TX). A two-tailed p-value of less than .05 was considered statistically significant. In bivariate analyses, continuous and categorical variables were compared using the Student t-test and chi-squared test, respectively.
To evaluate the independent impact of the different bowel preps on tolerability and cleansing effectiveness, we performed multivariable regression models with random effects to adjust for confounding. For our primary outcomes of total BBPS score and adequate bowel cleansing, we used linear and logistic regressions, respectively, to calculate adjusted p-values and odds ratios (OR) with 95% confidence intervals (CI). Both models adjusted for prep- (type of prep, completion, dosing), procedure- (procedure in addition to colonoscopy, fellow involvement, withdrawal time), and patient-level characteristics (demographics, body mass index, medication use, relevant comorbidities) as well as accounted for individual endoscopist-level factors via random effects. For the secondary outcome of prep tolerability, the logistic regression model with random effects adjusted for prep-, individual provider-, and patient-level covariates. In all analyses, GoLYTELY® served as the baseline comparator prep as it is the criterion standard according to the American Society for Gastrointestinal Endoscopy (ASGE).(12) We also performed subgroup analyses stratified by prep dosing; the above regression analyses were conducted among those who were prescribed day-before prep dosing as well as those given a split prep.
RESULTS
Study Population
Overall, 5253 outpatient colonoscopies were performed between August 4, 2016 to July 31, 2018. We excluded 914 cases that met exclusion criteria or had missing data: patient age <18 years (n=257); use of two-day bowel prep or unknown prep dosing (n=184); BBPS could not be completely scored because of either surgically absent colon segments or early procedural termination for reasons unrelated to bowel prep (n=90); missing bowel prep or bowel cleansing score data (n=383). Therefore, our analytic sample included 4339 colonoscopies performed in 3908 patients. We describe the study cohort’s demographics in Table 1.
TABLE 1.
Demographics of the study population (N=4339).
| Variable | n | % |
|---|---|---|
| Age: | ||
| 18–49 y | 1087 | 25.1% |
| 50–64 y | 1763 | 40.6% |
| ≥65 y | 1489 | 34.3% |
| Gender: | ||
| Female | 2222 | 51.2% |
| Male | 2117 | 48.8% |
| Race/ethnicity: | ||
| Non-Hispanic white | 2952 | 68.0% |
| Non-Hispanic black | 499 | 11.5% |
| Latino | 425 | 9.8% |
| Asian | 278 | 6.4% |
| Other/unknown | 185 | 4.3% |
| Primarily English speaker | 3983 | 91.8% |
| Body mass index (kg/m2): | ||
| <25 | 1899 | 43.8% |
| 25–29.9 | 1312 | 30.2% |
| ≥30 | 1073 | 24.7% |
| Unknown | 55 | 1.3% |
| Opioid use | 677 | 15.6% |
| Tricyclic antidepressant use | 73 | 1.7% |
| Type I or II diabetes | 700 | 16.1% |
| Liver cirrhosis | 75 | 1.7% |
| Procedure in addition to colonoscopy | 1449 | 33.4% |
| Fellow trainee involvement | 614 | 14.2% |
| Withdrawal time: | ||
| ≥6 minutes | 3557 | 82.0% |
| <6 minutes | 265 | 6.1% |
| Unknown | 517 | 11.9% |
Performing Endoscopists
The colonoscopies were performed by 75 providers who have been independently practicing for a median of 11 years (interquartile range [IQR] 5 to 23; range 1 to 40). The cohort included 34 community general gastroenterologists (45.3%), 13 colorectal surgeons (17.3%), 6 academic general gastroenterologists (8.0%), 6 academic inflammatory bowel disease specialists (8.0%), 5 academic interventional endoscopists, (6.7%), 4 academic hepatologists (5.3%), 3 academic GI motility specialists (4.0%), 3 academic pediatric gastroenterologists (4.0%), and 1 community interventional endoscopist (1.3%). The median number of colonoscopies performed per physician was 25 (IQR 9 to 62; range 1 to 435).
Bowel Prep Regimens
Table 2 lists the bowel preps prescribed during the study period. The most commonly prescribed prep was Miralax® with Gatorade®, followed by GoLYTELY®, Suprep®, Moviprep®, and Prepopik®/Clenpiq®. Osmoprep® and magnesium citrate were used less often. With respect to dosing, 61.7% were single-dosed the day before and 38.3% were split-dosed.
TABLE 2.
Bowel prep and procedure-related characteristics (N=4339).
| Variable | n | % |
|---|---|---|
| Prescribed bowel prep: | ||
| GoLYTELY® * | 512 | 11.8% |
| Moviprep® | 293 | 6.8% |
| Miralax® with Gatorade® | 2703 | 62.3% |
| Prepopik®/Clenpiq® | 226 | 5.2% |
| Suprep® † | 470 | 10.8% |
| Magnesium citrate | 53 | 1.2% |
| Osmoprep® | 82 | 1.9% |
| Completely finished bowel prep | 3955 | 91.2% |
| Bowel prep dosing: | ||
| Day-before dosing | 2676 | 61.7% |
| Split dosing | 1663 | 38.3% |
Also includes Colyte®, NuLYTELY®, and Trilyte®.
Also includes Suclear®.
Among the 75 endoscopists, the median number of prep types ordered was 4 (IQR 2 to 5; range 1 to 7). The proportion of providers who had prescribed each prep was as follows: Miralax® with Gatorade® (88.0%, n=66); GoLYTELY® (72.0%, n=54); Suprep® (60.0%, n=45); Moviprep® (49.3%, n=37); Prepopik®/Clenpiq® (48.0%, n=36); magnesium citrate (34.7%, n=26); Osmoprep® (17.3%, n=13).
Bowel Prep Tolerability
Among the 4339 colonoscopies, data on bowel prep completion were available for 4299 cases. Patients reported fully completing the prep in 92.0% (n=3955) of cases. Completion rates varied among the preps, as follows: Prepopik®/Clenpiq® (99.1%, n=221); magnesium citrate (98.1%, n=51); Suprep® (94.4%, n=439); Osmoprep® (92.7%, n=76); Miralax® with Gatorade® (92.6%, n=2487); Moviprep® (91.4%, n=264); GoLYTELY® (82.9%, n=417). After adjusting for prep-, provider-, and patient-related factors in multivariable logistic regression analysis with random effects, we found that patients receiving Prepopik®/Clenpiq® (p<.001), magnesium citrate (p=.014), Suprep® (p<.001), Osmoprep® (p=.003), Miralax® with Gatorade® (p<.001), and Moviprep® (p=.001) were all significantly more likely to complete the prep vs. those prescribed GoLYTELY®.
When compared to single dose, day-before preps (91.4%, n=2423), no difference in compliance was observed for split preps (92.9%, n=1532; p=.73). Conversely, males (94.3%, n=1977) were more likely to fully ingest the prep vs. females (89.8%, n=1978; p<.001). The remaining patient demographic factors were not significantly associated with bowel prep tolerability.
Subgroup Analysis – Stratification by Prep Dosing
We performed subgroup analyses among those prescribed day-before prep dosing (n=2650) as well as those given a split prep (n=1649). For day-before dosing, we found differential completions rates among the different preps when compared to GoLYTELY® (83.1%, n=304) after adjusting for prep, provider, and patient factors: Prepopik®/Clenpiq® (98.5%, n=128; p<.001); magnesium citrate (97.0%, n=32; p=.05); Osmoprep® (96.8%, n=61; p=.002); Suprep® (94.0%, n=233; p<.001); Miralax® with Gatorade® (92.1%, n=1509; p<.001); Moviprep® (91.2%, n=156; p=.03).
Even among those prescribed a split prep, we still found significant differences in tolerability vs. GoLYTELY® (82.5%, n=113): Prepopik®/Clenpiq® (100%, n=93; p<.001); magnesium citrate (100%, n=19; p<.001); Suprep® (94.9%, n=206; p<.001); Miralax® with Gatorade® (93.5%, n=978; p<.001); Moviprep® (91.5%, n=108; p=.02). However, no difference was seen for Osmoprep® (79.0%, n=15; p=.97).
Bowel Cleansing Outcomes – Overall
Overall, the average BBPS score was 7.05 ± 1.68 and 3942 (90.9%) had adequate bowel cleansing (i.e., total BBPS score ≥6 with each segment BBPS score ≥2). Scores had the following distribution: 0 (0.2%, n=10); 1 (0.2%, n=9); 2 (0.1%, n=6); 3 (3.3%, n=145); 4 (1.3%, n=56); 5 (3.5%, n=152); 6 (41.9%, n=1819); 7 (6.1%, n=265); 8 (11.3%, n=491); 9 (31.9%, n=1386). The average withdrawal time associated with each prep was the following: GoLYTELY® (19.7 ± 13.8 mins); Miralax® with Gatorade® (19.3 ± 15.8 mins); Osmoprep® (17.6 ± 9.8 mins); magnesium citrate (17.0 ± 14.1 mins); Moviprep® (17.0 ± 11.3 mins); Prepopik®/Clenpiq® (14.9 ± 9.8 mins); Suprep® (14.6 ± 9.3 mins).
Table 3 presents findings from the multivariable regressions on BBPS total score and adequate bowel cleansing. With respect to BBPS total score, Moviprep® (p=.004), Miralax® with Gatorade® (p<.001), and Suprep® (p<.001) had significantly higher scores when compared to GoLYTELY®, even after adjusting for confounders. No differences were seen among the remaining preps. Those prescribed split prep dosing (p=.001) also had higher BBPS total scores. Conversely, males (p<.001), opioid (p<.001) and tricyclic antidepressant users (p=.005), and those with diabetes (p=.001) and liver cirrhosis (p=.005) had lower bowel cleansing scores.
TABLE 3.
Multivariable regressions on BBPS total score and adequate bowel cleansing (N=4339).
| Variable | BBPS total score mean ± SD |
Adjusted p-value * | Adequate bowel cleansing †
n (%) |
OR [95% CI] * | |
|---|---|---|---|---|---|
| Prescribed bowel prep: | |||||
| GoLYTELY® | 6.67 ± 1.87 | reference | 430 (84.0%) | reference | |
| Moviprep® | 7.11 ± 1.62 | .004 | 267 (91.1%) | 1.44 [0.85–2.44] | |
| Miralax® with Gatorade® | 7.09 ± 1.64 | <.001 | 2499 (92.5%) | 1.76 [1.24–2.49] | |
| Prepopik®/Clenpiq® | 7.01 ± 1.59 | .18 | 205 (90.7%) | 1.24 [0.70–2.21] | |
| Suprep® | 7.28 ± 1.66 | <.001 | 426 (90.6%) | 1.37 [0.86–2.16] | |
| Magnesium citrate | 6.89 ± 1.56 | .39 | 48 (90.6%) | 1.54 [0.57–4.17] | |
| Osmoprep® | 7.04 ± 1.86 | .27 | 67 (81.7%) | 0.70 [0.36–1.37] | |
| Bowel prep completion: | |||||
| Did not complete prep | 6.89 ± 1.88 | reference | 298 (86.6%) | reference | |
| Fully completed prep | 7.07 ± 1.66 | .23 | 3606 (91.2%) | 1.36 [0.96–1.93] | |
| Unknown | 7.43 ± 1.52 | .07 | 38 (95.0%) | 2.82 [0.64–12.37] | |
| Bowel prep dosing: | |||||
| Day-before dosing | 6.97 ± 1.70 | reference | 2392 (89.4%) | reference | |
| Split dosing | 7.18 ± 1.63 | .001 | 1550 (93.2%) | 1.35 [1.05–1.74] | |
| Procedure in addition to colonoscopy: | |||||
| No | 7.09 ± 1.65 | reference | 2647 (91.6%) | reference | |
| Yes | 6.99 ± 1.74 | .19 | 1295 (89.4%) | 0.82 [0.65–1.04] | |
| Fellow involvement: | |||||
| No | 7.07 ± 1.68 | reference | 3390 (91.0%) | reference | |
| Yes | 6.98 ± 1.66 | .59 | 552 (89.9%) | 0.96 [0.70–1.31] | |
| Withdrawal time: | |||||
| ≥6 minutes | 7.12 ± 1.62 | reference | 3253 (91.5%) | reference | |
| <6 minutes | 7.31 ± 1.68 | .08 | 250 (94.3%) | 1.42 [0.80–2.50] | |
| Unknown | 6.48 ± 1.97 | <.001 | 439 (84.9%) | 0.55 [0.42–0.74] | |
| Age: | |||||
| 18–49 y | 7.11 ± 1.73 | reference | 976 (89.8%) | reference | |
| 50–64 y | 7.08 ± 1.71 | .74 | 1600 (90.8%) | 1.06 [0.79–1.42] | |
| ≥65 y | 6.98 ± 1.61 | .15 | 1366 (91.7%) | 1.09 [0.79–1.50] | |
| Gender: | |||||
| Female | 7.16 ± 1.66 | reference | 2034 (91.5%) | reference | |
| Male | 6.95 ± 1.69 | <.001 | 1908 (90.1%) | 0.82 [0.65–1.02] | |
| Race/ethnicity: | |||||
| Non-Hispanic white | 7.05 ± 1.66 | reference | 2687 (91.0%) | reference | |
| Non-Hispanic black | 6.87 ± 1.78 | .07 | 450 (90.2%) | 0.87 [0.61–1.24] | |
| Latino | 7.05 ± 1.74 | .51 | 373 (87.8%) | 0.71 [0.49–1.02] | |
| Asian | 7.35 ± 1.57 | .002 | 259 (93.2%) | 1.42 [0.85–2.37] | |
| Other/unknown | 7.15 ± 1.65 | .35 | 173 (93.5%) | 1.44 [0.78–2.69] | |
| Primarily language: | |||||
| English speaker | 7.07 ± 1.68 | reference | 3623 (91.0%) | reference | |
| Non-English speaker | 6.92 ± 1.69 | .51 | 319 (89.6%) | 1.08 [0.71–1.66] | |
| Body mass index (kg/m2): | |||||
| <25 | 7.04 ± 1.68 | reference | 1712 (90.2%) | reference | |
| 25–29.9 | 7.13 ± 1.66 | .005 | 1202 (91.6%) | 1.25 [0.96–1.62] | |
| ≥30 | 6.97 ± 1.69 | .60 | 976 (91.0%) | 1.23 [0.93–1.64] | |
| Unknown | 7.29 ± 1.67 | .51 | 52 (94.6%) | 1.72 [0.52–5.70] | |
| Opioid use: | |||||
| No | 7.12 ± 1.62 | reference | 3371 (92.1%) | reference | |
| Yes | 6.69 ± 1.91 | <.001 | 571 (84.3%) | 0.51 [0.39–0.65] | |
| Tricyclic antidepressant use: | |||||
| No | 7.06 ± 1.67 | reference | 3884 (91.1%) | reference | |
| Yes | 6.47 ± 1.99 | .005 | 58 (79.5%) | 0.36 [0.20–0.67] | |
| Type I or II diabetes: | |||||
| No | 7.11 ± 1.67 | reference | 3322 (91.3%) | reference | |
| Yes | 6.79 ± 1.72 | .001 | 620 (88.6%) | 0.76 [0.56–1.03] | |
| Liver cirrhosis: | |||||
| No | 7.07 ± 1.67 | reference | 3886 (91.1%) | reference | |
| Yes | 6.29 ± 1.79 | .005 | 56 (74.7%) | 0.45 [0.24–0.83] | |
BBPS, Boston Bowel Preparation Scale; CI, confidence interval; OR, odds ratio; SD, standard deviation.
The multivariable linear and logistic regression models with random effects included all variables in the table.
Adequate bowel cleansing was defined as total BBPS score ≥6 with each segment BBPS score ≥2.
We noted the following adequate bowel cleansing rates for each prep: Miralax® with Gatorade® (92.5%, n=2499); Moviprep® (91.1%, n=267); Prepopik®/Clenpiq® (90.7%, n=205); Suprep® (90.6%, n=426); magnesium citrate (90.6%, n=48); GoLYTELY® (84.0%, n=430); Osmoprep® (81.7%, n=67). Even after adjusting for prep-, procedure-, endoscopist-, and patient-level factors, we found that Miralax® with Gatorade® (OR 1.76, 95% CI 1.24 to 2.49) had higher odds for adequate cleansing when compared to GoLYTELY®. Although Moviprep® and Suprep® had numerically higher BBPS scores vs. GoLYTELY®, the difference in adequate bowel cleansing rates was not significant. We also found no differences among the remaining preps.
The odds of adequate bowel cleaning was higher in patients receiving split dosing (OR 1.35, 95% CI 1.05 to 1.74). In contrast, adequate bowel cleaning was lower in those taking opioids (OR 0.51, 95% CI 0.39 to 0.65) and tricyclic antidepressants (OR 0.36, 95% CI 0.20 to 0.67), and those with liver cirrhosis (OR 0.45, 95% CI 0.24 to 0.83).
Subgroup Analysis – Stratification by Prep Dosing
We performed subgroup analyses among those prescribed day-before prep dosing (n=2676; Supplementary Table 1) as well as those given a split prep (n=1663; Supplementary Table 2). Of those who had day-before dosing, we found that Moviprep® (p=.007), Miralax® with Gatorade® (p<.001), and Suprep® (p<.001) had significantly higher BBPS total scores vs. GoLYTELY®. However, only Miralax® with Gatorade® was associated with increased odds for adequate bowel cleansing (OR 1.99, 95% CI 1.36 to 2.92) when compared to GoLYTELY®. Among those with split prep dosing, we found that Osmoprep® was associated with lower odds for adequate bowel cleansing (OR 0.14, 95%CI 0.04 to 0.51) vs. GoLYTELY®. No significant differences were seen among the remaining preps with respect to BBPS total scores or rates of adequate bowel cleansing.
Bowel Cleansing Outcomes – By Colon Segment
Table 4 includes findings from the multivariable logistic regression analysis among the overall cohort predicting adequate bowel cleansing rates for each colon segment, stratified by the individual preps. Miralax® with Gatorade® had significantly higher satisfactory bowel cleansing rates for all segments of the colon when compared to GoLYTELY®. Suprep® had higher rates for the transverse and left colon while Moviprep had improved cleansing for the transverse colon. No significant differences were seen for the remaining preps.
TABLE 4.
Multivariable regression on adequate bowel cleansing rates by colon segment (i.e., BBPS ≥2) (N=4339).
| Prescribed bowel prep | Right colon | Transverse colon | Left colon | |||||
|---|---|---|---|---|---|---|---|---|
| Adequate bowel cleansing n (%) |
OR [95% CI] * | Adequate bowel cleansing n (%) |
OR [95% CI] * | Adequate bowel cleansing n (%) |
OR [95% CI] * | |||
| GoLYTELY® | 444 (86.7%) | reference | 464 (90.6%) | reference | 461 (90.0%) | reference | ||
| Moviprep® | 270 (92.2%) | 1.30 [0.75–2.28] | 281 (95.9%) | 2.06 [1.04–4.07] | 279 (95.2%) | 1.74 [0.92–3.28] | ||
| Miralax® with Gatorade® | 2526 (93.5%) | 1.61 [1.11–2.35] | 2584 (95.6%) | 1.97 [1.33–2.92] | 2575 (95.3%) | 1.80 [1.23–2.62] | ||
| Prepopik®/Clenpiq® | 207 (91.6%) | 1.08 [0.59–1.98] | 218 (96.5%) | 2.05 [0.92–4.59] | 218 (96.5%) | 2.05 [0.92–4.55] | ||
| Suprep® | 433 (92.1%) | 1.40 [0.85–2.29] | 452 (96.2%) | 2.19 [1.21–3.99] | 451 (96.0%) | 2.02 [1.13–3.61] | ||
| Magnesium citrate | 48 (90.6%) | 1.23 [0.45–3.38] | 50 (94.3%) | 1.71 [0.49–5.94] | 52 (98.1%) | 5.22 [0.69–39.36] | ||
| Osmoprep® | 67 (81.7%) | 0.55 [0.28–1.10] | 77 (93.9%) | 1.33 [0.48–3.64] | 76 (92.7%) | 1.02 [0.40–2.61] | ||
BBPS, Boston Bowel Preparation Scale; CI, confidence interval; OR, odds ratio.
The multivariable logistic regression model with random effects adjusted for all prep-, procedure-, and patient-level factors seen in Table 3
Split prep dosing was associated with improved cleansing rates in the right (OR 1.33, 95% CI 1.02 to 1.74), transverse (OR 1.56, 95% CI 1.11 to 2.17), and left colon (OR 1.46, 95% CI 1.07 to 2.01) vs. day-before dosing. Males (right – OR 0.73, 95% CI 0.58 to 0.93; transverse – OR 0.69, 95% CI 0.51 to 0.93; left – OR 0.74, 95% CI 0.56 to 0.99) and those on opioids (right – OR 0.48, 95% CI 0.36 to 0.62; transverse – OR 0.47, 95% CI 0.34 to 0.65; left – OR 0.48, 95% CI 0.35 to 0.66) had lower adequate cleansing rates throughout the colon. Patients on tricyclic antidepressants also had worse cleansing in the right (OR 0.38, 95% CI 0.20 to 0.72), transverse (OR 0.26, 95% CI 0.13 to 0.51), and left colon segments (OR 0.36, 95% CI 0.17 to 0.74). Diabetics had inferior cleansing only in right colon (OR 0.71, 95% CI 0.52 to 0.98) while those with cirrhosis had lower odds for adequate cleansing only in the transverse (OR 0.45, 95% CI 0.22 to 0.95) and left colon (OR 0.38, 95% CI 0.19 to 0.76).
DISCUSSION
In this large, prospective comparative effectiveness study comparing the real-world effectiveness of seven commonly used bowel preps, we found that Miralax® with Gatorade®, Moviprep®, and Suprep® were better tolerated and associated with superior bowel cleansing when compared to GoLYTELY®. Consistent with previous research (18–23), we also found that split dosing improves the odds of adequate cleansing, whereas use of opioids and tricyclic antidepressants and presence of diabetes and cirrhosis are associated with worse cleansing.
The current study has several strengths. First, to our knowledge, this is the largest prospective, comparative effectiveness study evaluating the real-world tolerability and effectiveness of the available bowel preps. Our study included data from over 4300 outpatient colonoscopies performed by a diverse set of providers. Second, by leveraging Cedars-Sinai’s pluralistic structure where both academic and community-based clinicians are free to prescribe the bowel prep of their choice, we were able to compare outcomes among commonly used preps. This is in contrast to traditional RCTs, which usually compare a small number of bowel regimens in carefully controlled protocols, often with patient remuneration.(12) Third, our study cohort included all-comers undergoing an outpatient colonoscopy and reflects the population referred for endoscopy in everyday clinical practice. Prior RCTs typically excluded patients with chronic opioid use, inflammatory bowel disease, chronic kidney disease, congestive heart failure, and cirrhosis, among others.(24–28) Fourth, and perhaps most importantly, the naturalistic and observational study design allowed us to determine how the available preps perform in clinical practice, free from the Hawthorne effect (i.e., observer bias). Prior bowel prep RCTs focused on efficacy and were performed in tightly controlled settings that do not closely mirror real-world conditions. For example, multiple RCTs have found that GoLYTELY®, a high volume 4 liter prep, has similar efficacy to comparator low-volume preps.(12) However, in these trials the Hawthorne effect and remuneration may have influenced patients in the GoLYTELY® arms to be more willing to fully ingest the prep, even despite its higher volume and unpalatable taste compared to other available formulations. In the absence of observer bias and protocolized monitoring, patients in everyday practice may be less likely to tolerate large volume and unsavory preps, leading to differential bowel cleansing as observed in this comparative effectiveness study.
We found that Miralax® with Gatorade® was prospectively associated with superior cleansing when compared to GoLYTELY®; this may result from an improved flavor profile and enhanced tolerability of the former regimen. Yet, prior studies have provided mixed results, as Miralax® with Gatorade® has been found to have either similar (24, 25, 29), better (30), and even worse (26, 31, 32) outcomes vs. GoLYTELY®. A meta-analysis using a fixed-effects model by Siddique and colleagues of 1418 patients concluded that Miralax® with Gatorade® is associated with lower bowel prep quality than GoLYTELY® (p=.04).(33) However, when Zhang employed random-effects using the same data, there is no significant difference between the groups (p=.19).(34) Our results contrast with prior findings, as we found that Miralax® with Gatorade® is associated with higher total BBPS scores when compared to the GoLYTELY® reference standard. Again, this discrepancy may result from differences between comparative efficacy vs. effectiveness studies. In the absence of careful oversight and study protocols, patients in our study revealed lower tolerability of GoLYTELY® which likely influenced its suboptimal bowel cleansing results. However, we should mention that while Miralax® with Gatorade® (7.09 ± 1.64) has a statistically higher average total BBPS score vs. GoLYTELY® (6.67 ± 1.87), the impact of this difference on clinical outcomes is unclear. To our knowledge, the minimal clinically important difference for total BBPS score with respect to outcomes such as ADR and interval CRC has not been defined. Because of this issue, we also opted to asses adequate bowel cleansing rates as an outcome (Miralax® with Gatorade® 92.5% vs. GoLYTELY® 84.0%). While a process measure, it is nonetheless important as those with inadequate bowel cleansing (i.e., BBPS <6) should undergo a repeat colonoscopy within 1 year (12), thereby leading to increased healthcare utilization and costs and failure to detect prevalent lesions.(35)
It is important to note that while Miralax® with Gatorade® is commonly used in clinical practice and recognized by the ASGE (12), it is not approved by the U.S. FDA as a colonoscopy purgative. There are also concerns that it is hyposmotic and can result in hyponatremia.(17) When formally studied, though, Miralax® with Gatorade® does not lead to clinically significant electrolyte changes from baseline when compared to GoLYTELY®.(24, 25, 29) Moreover, when collectively studied in a meta-analysis, no differences are seen between the preps for side effects including nausea, cramping, and bloating.(33)
We also found that Suprep® – a low volume, sodium sulfate-based bowel prep approved by the U.S. FDA – is associated with superior tolerability and cleansing when compared to GoLYTELY®. Our results are consistent with an RCT by Rex and colleagues that found that patients taking Suprep® have improved bowel prep quality vs. NuLYTELY®.(36) We also noted that Moviprep® similarly is associated with better tolerability and cleansing. However, for the remaining preps (i.e., magnesium citrate, Osmoprep®, and Prepopik®/Clenpiq®), we found that patients are more likely to fully ingest these formulations in comparison to GoLYTELY® but found no significant differences in bowel cleansing. Our findings are similar to prior RCTs and meta-analyses that also found Osmoprep® (37) and Prepopik® (38) to be non-inferior but better tolerated than GoLYTELY®. It is also worth mentioning that nearly 100% of patients fully completed magnesium citrate which is likely a function of its very low volume. While we could not assess for significant differences in bowel cleansing outcomes due to its small sample size, magnesium citrate appears to at least lead to comparable bowel cleansing when compared to 4 liters of GoLYTELY®. Of note, the prep’s low use at our institution may reflect recommendations by the ASGE to avoid its use in those with renal insufficiency and in the elderly as well as the fact that it is not a U.S. FDA-approved bowel prep.(12)
Our study also confirmed several factors known to impact bowel cleansing. We found that split dosing increases the odds of adequate cleansing compared to day-before dosing, which is consistent with a meta-analysis of 47 RCTs with 13,487 patients by Martel and colleagues.(18) Although split prep dosing has definitively been shown to improve bowel cleanliness, only 38% of cases in our study employed this regimen, suggesting persistent under-use of a dosing schedule that improves bowel cleansing (18) and ADR (39). Further research is needed to assess use of and barriers to split prep dosing at other institutions, particularly those with a pluralistic structure, as well as to develop strategies for improving implementation and uptake. It is also worth noting that in our subgroup analysis among those with split prep dosing, the differences in BBPS total scores and adequate bowel cleansing rates among the various bowel preps largely were no longer statistically significant. While this may be a function of reduced power due to smaller sample sizes, this remains an area worthy of continued research as use of split prep dosing becomes more prevalent. We also found that male gender, opioid use, tricyclic antidepressant use, diabetes, and cirrhosis are all associated with worse cleansing, as observed in prior studies.(19–23, 40, 41) Other factors noted to lead to higher odds for inadequate bowel prep, but not adjusted for in our analysis, include lower educational attainment, constipation, hypertension, Parkinson’s disease, and stroke/dementia.(40, 41) However, in contradistinction to these two prior studies (40, 41), we did not find significant associations between bowel cleansing and age and BMI.
Our study has limitations. First, this was a single site study and may not be generalizable to other medical centers and healthcare systems. However, the large sample size and diverse provider and patient cohorts lend generalizability. Second, blinded reviewers could not confirm the accuracy of the nurses’ BBPS scores or assess for inter-observer differences for each case, as labeling of endoscopic images and bowel cleansing documentation was not systematically performed by the 75 endoscopists. However, this pragmatic study reflects everyday clinical practice and was designed to avoid risk of observer bias that might arise by stationing study staff in the procedure rooms. Relying on nurses’ BBPS assessments also may be a strength as they employ the scale on a regular basis; some physicians in our study either may not know how to properly apply the BBPS or use a different scoring system (e.g., Ottawa Bowel Preparation Scale, Aronchick Scale, etc.) We also would expect any inaccurate BBPS scoring to have been evenly distributed among the various prep groups, so it thereby should not have impacted the regression analyses. Regardless, we sought to address this limitation by holding in-service training with the endoscopy lab staff to ensure consistent and appropriate scoring among the evaluators. The nurses’ BBPS module in the EHR also included hover text for each score further supporting continued appropriate scoring after the in-services as well as for new staff. Moreover, our results identified many of the same predictors of bowel prep quality as seen in previous studies (e.g., split dosing, opioids, tricyclic antidepressants, diabetes, cirrhosis), offering further evidence of generalizability and accuracy of nurse-based BBPS recordings. Third, procedure nurses were not blinded to the prescribed preps documented by the pre-procedure nurses. However, documentation of preps and BBPS scoring is standard of care in our center, and it is unlikely that the nurses had intrinsic preferences for one prep formulation over another. There were also over 40 nurses who rotated through the multiple procedure rooms in the endoscopy unit during the study period; we would not expect systematic and significant scoring bias to have occurred among the staff. Fourth, there may have been confounding related to variable bowel cleanliness thresholds among the 75 endoscopists. In other words, the findings could have been biased if certain preps were only used by a limited number of proceduralists who were aggressive at washing and cleansing the colon on withdrawal. Along the same lines, some endoscopists may have provided input on the BBPS score entered in the nurses’ EHR BBPS module, although the nurses stated that these occurrences were rare. We addressed these potential limitations by employing multivariable regression with random effects to account for clustering and unmeasurable factors as it related to the individual proceduralists (e.g., endoscopic skills and experience, personal bowel cleanliness thresholds, patient population, etc.). The impact of this bias is also limited due to the wide distribution of preps used among the 75 endoscopists; the 4 preps with differential bowel cleansing (i.e., GoLYTELY®, Miralax® with Gatorade®, Moviprep®, and Suprep®) were used by 49% to 88% of physicians. Finally, we were unable to identify the preps taken by patients who either no-showed or canceled their procedure at the last minute. Those prescribed large volume and unpalatable purgatives may not have tolerated them while at home, leading to early termination and missing their appointment. Thus, we may have underestimated the differences in tolerability and bowel cleansing between GoLYTELY® and the other preps.
In summary, our study reveals that Miralax® with Gatorade®, Moviprep®, and Suprep® are better tolerated and associated with superior bowel cleansing compared to GoLYTELY®. Future large, pragmatic, multicenter comparative effectiveness studies are needed to confirm these findings and to extend them to evaluate impact on other outcomes, including ADR, cancer detection, and cancer prevention.
Supplementary Material
STUDY HIGHLIGHTS.
What is current knowledge?
There is a wide variety of commercially available colonoscopy bowel prep regimens, each varying in volume, tolerability, and formulation.
National societies provide minimal guidance regarding which preps are best tolerated and most effective; current guidelines only recommend accounting for a patient’s medical history, medications, and prior procedure history when selecting a prep.
Non-specific guidance reflects a lack of comparative effectiveness studies that directly evaluate preps in a “real world” setting; most data are from randomized trials of a limited number of preps in the context of tightly controlled research protocols that may not accurately reflect real-world conditions.
What is new here?
In a large-scale, prospective, commercially unfunded, comparative effectiveness study of 4339 colonoscopies, there was differential tolerability and bowel cleansing effectiveness among seven commonly available bowel preps.
Miralax® with Gatorade®, Moviprep®, and Suprep® were better tolerated and prospectively associated with superior bowel cleansing when compared to GoLYTELY® in everyday clinical practice.
Acknowledgements:
The authors would like to thank and acknowledge Kayle Tramel, RN, BS, MSN, CAPA, for her support in the conduct of the study.
Financial Support:
This study was supported by a Cedars-Sinai Clinical and Translational Science Institute (CTSI) Clinical Scholars Grant. Dr. Almario is supported by a career development award from the American College of Gastroenterology. Drs. Almario and Spiegel are supported by a NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881. The Cedars-Sinai Center for Outcomes Research and Education (CS-CORE) is supported by The Marc and Sheri Rapaport Fund for Digital Health Sciences & Precision Health.
Potential Competing Interests:
Dr. Christopher Almario received a consulting fee from Bayer U.S. Dr. Brennan Spiegel received consulting fees from Ferring Pharmaceuticals and Valeant Pharmaceuticals. The remaining authors do not have any relevant disclosures.
REFERENCES
- 1.American Cancer Society. Cancer Facts & Figures 2017 Atlanta, GA: American Cancer Society; 2017. [Google Scholar]
- 2.Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016;315:2564–2575. [DOI] [PubMed] [Google Scholar]
- 3.Selby JV, Friedman GD, Quesenberry CP, et al. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653–7. [DOI] [PubMed] [Google Scholar]
- 4.Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977–81. [DOI] [PubMed] [Google Scholar]
- 5.Müller AD, Sonnenberg A. Protection by endoscopy against death from colorectal cancer. A case-control study among veterans. Arch Intern Med 1995;155:1741–8. [DOI] [PubMed] [Google Scholar]
- 6.Seeff LC, Richards TB, Shapiro JA, et al. How many endoscopies are performed for colorectal cancer screening? Results from CDC’s survey of endoscopic capacity. Gastroenterology 2004;127:1670–7. [DOI] [PubMed] [Google Scholar]
- 7.Rex DK, Schoenfeld PS, Cohen J, et al. Quality indicators for colonoscopy. Am J Gastroenterol 2015;110:72–90. [DOI] [PubMed] [Google Scholar]
- 8.Froehlich F, Wietlisbach V, Gonvers JJ, et al. Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study. Gastrointest Endosc 2005;61:378–84. [DOI] [PubMed] [Google Scholar]
- 9.Harewood GC, Sharma VK, de Garmo P. Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia. Gastrointest Endosc 2003;58:76–9. [DOI] [PubMed] [Google Scholar]
- 10.Corley DA, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014;370:1298–306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Johnson DA, Barkun AN, Cohen LB, et al. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2014;109:1528–45. [DOI] [PubMed] [Google Scholar]
- 12.Saltzman JR, Cash BD, Pasha SF, et al. Bowel preparation before colonoscopy. Gastrointest Endosc 2015;81:781–94. [DOI] [PubMed] [Google Scholar]
- 13.Spiegel BM, Talley J, Shekelle P, et al. Development and validation of a novel patient educational booklet to enhance colonoscopy preparation. Am J Gastroenterol 2011;106:875–83. [DOI] [PubMed] [Google Scholar]
- 14.Bromley EG, May FP, Federer L, et al. Explaining persistent under-use of colonoscopic cancer screening in African Americans: A systematic review. Prev Med 2014;71c:40–48. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Calderwood AH, Jacobson BC. Comprehensive validation of the Boston Bowel Preparation Scale. Gastrointest Endosc 2010;72:686–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Lai EJ, Calderwood AH, Doros G, et al. The Boston bowel preparation scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009;69:620–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Gerard DP, Holden JL, Foster DB, et al. Randomized Trial of Gatorade/Polyethylene Glycol With or Without Bisacodyl and NuLYTELY for Colonoscopy Preparation. Clin Transl Gastroenterol 2012;3:e16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Martel M, Barkun AN, Menard C, et al. Split-Dose Preparations Are Superior to Day-Before Bowel Cleansing Regimens: A Meta-analysis. Gastroenterology 2015;149:79–88. [DOI] [PubMed] [Google Scholar]
- 19.Ness RM, Manam R, Hoen H, et al. Predictors of inadequate bowel preparation for colonoscopy. Am J Gastroenterol 2001;96:1797–802. [DOI] [PubMed] [Google Scholar]
- 20.Lebwohl B, Wang TC, Neugut AI. Socioeconomic and other predictors of colonoscopy preparation quality. Digestive Diseases & Sciences 2014;55:2014–20. [DOI] [PubMed] [Google Scholar]
- 21.Chung YW, Han DS, Park KH, et al. Patient factors predictive of inadequate bowel preparation using polyethylene glycol: a prospective study in Korea. J Clin Gastroenterol 2009;43:448–52. [DOI] [PubMed] [Google Scholar]
- 22.Fayad NF, Kahi CJ, Abd El-Jawad KH, et al. Association between body mass index and quality of split bowel preparation. Clin Gastroenterol Hepatol 2013;11:1478–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Dik VK, Moons LM, Huyuk M, et al. Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score. Gastrointest Endosc 2015;81:665–72. [DOI] [PubMed] [Google Scholar]
- 24.McKenna T, Macgill A, Porat G, et al. Colonoscopy preparation: polyethylene glycol with Gatorade is as safe and efficacious as four liters of polyethylene glycol with balanced electrolytes. Dig Dis Sci 2012;57:3098–105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Samarasena JB, Muthusamy VR, Jamal MM. Split-dosed MiraLAX/Gatorade is an effective, safe, and tolerable option for bowel preparation in low-risk patients: a randomized controlled study. Am J Gastroenterol 2012;107:1036–42. [DOI] [PubMed] [Google Scholar]
- 26.Enestvedt BK, Fennerty MB, Eisen GM. Randomised clinical trial: MiraLAX vs. Golytely - a controlled study of efficacy and patient tolerability in bowel preparation for colonoscopy. Aliment Pharmacol Ther 2011;33:33–40. [DOI] [PubMed] [Google Scholar]
- 27.Bitoun A, Ponchon T, Barthet M, et al. Results of a prospective randomised multicentre controlled trial comparing a new 2-L ascorbic acid plus polyethylene glycol and electrolyte solution vs. sodium phosphate solution in patients undergoing elective colonoscopy. Aliment Pharmacol Ther 2006;24:1631–42. [DOI] [PubMed] [Google Scholar]
- 28.Manes G, Repici A, Hassan C. Randomized controlled trial comparing efficacy and acceptability of split- and standard-dose sodium picosulfate plus magnesium citrate for bowel cleansing prior to colonoscopy. Endoscopy 2014;46:662–9. [DOI] [PubMed] [Google Scholar]
- 29.Matro R, Daskalakis C, Negoianu D, et al. Randomised clinical trial: Polyethylene glycol 3350 with sports drink vs. polyethylene glycol with electrolyte solution as purgatives for colonoscopy--the incidence of hyponatraemia. Aliment Pharmacol Ther 2014;40:610–9. [DOI] [PubMed] [Google Scholar]
- 30.Shieh FK, Gunaratnam N, Mohamud SO, et al. MiraLAX-Gatorade bowel prep versus GoLytely before screening colonoscopy: an endoscopic database study in a community hospital. J Clin Gastroenterol 2012;46:e96–e100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Enestvedt BK, Brian Fennerty M, Zaman A, et al. MiraLAX vs. Golytely: is there a significant difference in the adenoma detection rate? Aliment Pharmacol Ther 2011;34:775–82. [DOI] [PubMed] [Google Scholar]
- 32.Hjelkrem M, Stengel J, Liu M, et al. MiraLAX is not as effective as GoLytely in bowel cleansing before screening colonoscopies. Clin Gastroenterol Hepatol 2011;9:326–332.e1. [DOI] [PubMed] [Google Scholar]
- 33.Siddique S, Lopez KT, Hinds AM, et al. Miralax with gatorade for bowel preparation: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2014;109:1566–74. [DOI] [PubMed] [Google Scholar]
- 34.Zhang Z Is polyethylene glycol superior to miralax-gatorade in bowel preparations for colonoscopy? Am J Gastroenterol 2015;110:596–7. [DOI] [PubMed] [Google Scholar]
- 35.Chokshi RV, Hovis CE, Hollander T, et al. Prevalence of missed adenomas in patients with inadequate bowel preparation on screening colonoscopy. Gastrointest Endosc 2012;75:1197–203. [DOI] [PubMed] [Google Scholar]
- 36.Rex DK, Di Palma JA, Rodriguez R, et al. A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy. Gastrointest Endosc 2010;72:328–36. [DOI] [PubMed] [Google Scholar]
- 37.Chaussade S, Schmocker C, Toulemonde P, et al. Phosphate tablets or polyethylene glycol for preparation to colonoscopy? A multicentre non-inferiority randomized controlled trial. Surg Endosc 2017;31:2166–2173. [DOI] [PubMed] [Google Scholar]
- 38.Kao D, Lalor E, Sandha G, et al. A randomized controlled trial of four precolonoscopy bowel cleansing regimens. Can J Gastroenterol 2011;25:657–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Radaelli F, Paggi S, Hassan C, et al. Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme. Gut 2015. [DOI] [PubMed] [Google Scholar]
- 40.Gandhi K, Tofani C, Sokach C, et al. Patient Characteristics Associated With Quality of Colonoscopy Preparation: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018;16:357–369.e10. [DOI] [PubMed] [Google Scholar]
- 41.Hassan C, Fuccio L, Bruno M, et al. A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy. Clin Gastroenterol Hepatol 2012;10:501–6. [DOI] [PubMed] [Google Scholar]
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