Harefield Cleansing Scale Research Articles

Performance of bowel preparation quality scales in patients with Crohn's disease.

The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown. To evaluate the operating properties of instruments used to assess BP quality in patients with CD. We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100-mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES-CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within-patient correlation between instruments and the visual analogue scale using mixed-effect models. The correlation between BP quality and SES-SD scores was assessed using Spearman's rho. Inter- and intra-rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter-rater reliability ICC ≥0.41). The visual analogue scale had substantial inter- and almost perfect (ICC ≥0.81) intra-rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated. Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD.

P477 Performance of bowel preparation quality scales in patients with Crohn’s disease

Abstract Background The performance of bowel preparation (BP) in patients with Crohn’s disease (CD) is unknown and may be suboptimal due to the presence of mucosal inflammation, strictures, pseudopolyps and bowel resection. We evaluated the reliability and validity of available BP scales in patients with CD. Methods Bowel preparation, in colonoscopy videos (N=50) from patients with CD (N=40) that represented a range of bowel preparation quality and endoscopic disease activity, was independently rated twice, separated by at least 2 weeks, by 3 central readers using the Boston Bowel Preparation Score (BBPS), modified BBPS, Harefield Cleansing Scale (HCS), Food and Drug Administration bowel cleansing assessment scale (FDA BCAS), and a 100-mm visual analogue scale (VAS) of bowel cleanliness. Endoscopic activity was assessed with the Simple Endoscopic Score for CD (SES-CD). All assessments were on endoscope insertion and withdrawal and in the ileum, right colon, transverse colon, left colon, and rectum to facilitate evaluation of the relationship between BP and SES-CD scores. Reliability of BP assessment was quantified using the intraclass correlation coefficient (ICC) and interpreted with benchmarks defined by Landis and Koch.1 Validity was assessed by within-patient correlation between each BP scale and the VAS across segments using mixed effect models. Correlation between BP quality and SES-SD scores by location was assessed using Spearman’s rho. Results Substantial (ICC ≥0.61) inter-rater reliability was observed for all BP scales and the VAS during insertion and withdrawal, except for the FDA BCAS, which had moderate (ICC ≥0.41) inter-rater reliability on insertion (Table 1). Intra-rater reliability was similarly substantial for all BP scales and almost perfect (ICC ≥0.81) for the VAS during insertion and withdrawal. Coefficients for the validity of all BP scales based on correlation with the VAS of bowel cleanliness exceeded 0.58 on both insertion and withdrawal. BP and endoscopic disease activity were negatively correlated in the colon, particularly in the left colon, suggesting that lower BP scores in this segment may result in higher SES-CD scores (Table 2). Conclusion Existing scales are reliable for the assessment of BP in patients with CD. These results provide a framework for scoring of BP quality in clinical trials for CD and support the inclusion of patients with CD for the evaluation of novel BP agents. Reference: 1. Landis J.R. and Koch G. G. Biometrics. 1977:33;159-74

An Expert Consensus to Standardize Assessment of Bowel Cleansing for Clinical Trials of Bowel Preparations for Crohn's Disease.

Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures. To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process. Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale. Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed. We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies.

Existing Bowel Preparation Quality Scales Are Reliable in the Setting of Centralized Endoscopy Reading.

Development of bowel preparation products has been based upon colon cleansing rating by a local endoscopist. It is unclear how bowel preparation scales perform when centrally evaluated. To evaluate the reliability of bowel preparation quality scales when assessed by central readers. Four central readers evaluated 52 videos in triplicate, 2weeks apart, during the entire endoscopic procedure (insertion/withdrawal of the colonoscope) and exclusively on colonoscope withdrawal using the Boston Bowel Preparation Scale (BBPS), Chicago Bowel Preparation scale, Harefield Cleansing Scale, Ottawa Bowel Preparation Quality Scale (OBPQS), Aronchick score, a visual analogue scale, and additional items proposed in a modified Research and Development/University of California Los Angeles appropriateness process. Reliability was assessed with intraclass correlation coefficients. Intraclass correlation coefficients (95% confidence interval) for inter-rater reliability of the quality scales ranged from 0.51 to 0.65 (consistent with moderate to substantial inter-rater reliability) during the entire procedure. Corresponding intraclass correlation coefficients for intra-rater reliability ranged from 0.69 to 0.77 (consistent with substantial intra-rater reliability). Reliability was highest in the right colon and lowest in the left colon. No differences were observed in reliability when assessed for the procedure overall (insertion/withdrawal) relative to assessment on withdrawal alone. All five bowel preparation quality scales had moderate to substantial inter-rater reliability. Panelists considered the Aronchick score too simplistic for clinical trials and recognized that assessment of residual fluid in the Ottawa Bowel Preparation Quality Scale was not amenable to central assessment.

Improving the tolerability and safety of 1-L polyethylene glycol plus low-dose ascorbic acid for bowel preparation in a healthy population: a randomized multicenter clinical trial

One-liter polyethylene glycol plus ascorbic acid (PEG-ASC) improves patient tolerability, but some patients still show low tolerability to a relatively high content of ASC. This study aimed to improve the tolerability and safety of 1-L PEG with low-dose ASC in comparison with standard 1-L and 2-L PEG-ASC. This was a randomized, controlled, double-blinded, multicenter, noninferiority trial involving 215 healthy adults who underwent colonoscopy from June 2020 to January 2021. Efficacy, tolerability, and safety were compared among 1-L PEG with low-dose ASC (50% lower ASC concentration in group A and 25% lower ASC concentration in groups B and C) and standard 1-L and 2-L PEG-ASC with all split regimens. One-liter PEG with low-dose ASC (groups A-C) had similar bowel cleansing efficacies according to the Harefield Cleansing Scale and Boston Bowel Preparation Scale, without negative clinical performance, compared with standard 1-L and 2-L PEG-ASC preparation (all P > .1). One-liter PEG with low-dose ASC had better tolerability compared with 2-L PEG-ASC and less residual fluid retention in the stomach compared with 1-L PEG-ASC, proportional to the amount of ASC. No significant differences were found in the incidences of overall adverse events, mild adverse events, or death or in the occurrence of gastroduodenal erosion or ulcer in upper endoscopy. One-liter PEG with low-dose ASC (25%-50% reduction in dose) for bowel cleansing showed similar efficacy and safety compared with standard 1-L or 2-L PEG-ASC, better tolerability compared with 2-L PEG-ASC, and less residual gastric fluid retention compared with standard 1-L PEG-ASC. (Clinical trial registration number: KCT0005490.).

Use of Insoluble Dietary Fiber and Probiotics for Bowel Preparation Before Colonoscopy: A Prospective Study.

Background:In screening colonoscopy, patients usually have to ingest large amounts of bowel-cleansing agents, including polyethylene glycol (PEG). This is difficult and has various side effects; thus, patients avoid undergoing a colonoscopy. We tested a novel bowel preparation method before colonoscopy using insoluble dietary fiber and probiotics (PB).Methods:This was a prospective clinical study conducted between October 2018 and March 2019 at a general hospital. Forty participants were randomly assigned to low-volume PEG solution diet (MoviPrep), wheat bran fiber (WBF) and probiotic Bifidobacterium animalis subsp. lactis GCL2505 (PB GCL2505), or standard-volume regimen (1.0 to 1.5 L of MoviPrep) (control group). The patient compliance and the quality of bowel preparation were evaluated.Results:Forty individuals aged 38 to 83 years were randomly assigned to the WBF with PB (n=20) and control (n=20) groups. All participants underwent bowel preparation before colonoscopy according to each protocol. The mean required volume of MoviPrep was significantly lower in the WBF with PB group than in the control group (582.5 vs. 1305 mL, P<0.0001). Successful bowel-cleansing rates were not significantly different between the 2 groups; however, the ratio of the Harefield Cleansing Scale grades C and D was significantly lower in the WBF with PB group than in the control group (P=0.0471).Conclusions:The intake of WBF and GCL2505 before colonoscopy reduces the required PEG quantities while maintaining bowel-cleansing quality. This novel, minimally invasive pretreatment method makes colonoscopy more accessible contributing to the prevention and early treatment of colorectal cancer.

1L NER1006 can improve rates of adequate and high-quality bowel cleansing in the right colon: a post hoc analysis of two randomised clinical trials

BackgroundThe right colon is difficult to cleanse compared with other colon segments. This post hoc analysis of two randomised clinical trials (MORA and NOCT) examined whether 1L polyethylene glycol (PEG) NER1006 and two mid-volume alternatives could improve adequate and high-quality cleansing in the right colon among patients with complete cleansing assessments.MethodsPatients received NER1006 (N2D), 2L PEG plus ascorbate (2LPEG) or oral sulphate solution (OSS) as a 2-day evening/morning split-dosing regimen or NER1006 as a same-day morning-only dosing regimen (N1D). Patients had full segmental scoring assigned by treatment-blinded central readers using the Harefield Cleansing Scale. The right colon adequate (score ≥ 2) and high-quality (score ≥ 3) cleansing success of NER1006 (N2D and N1D) versus 2LPEG and OSS was analysed individually and as pooled groups (N2D vs. 2LPEG/OSS). We assessed the comparative right colon cleansing rates of the N2D versus 2LPEG/OSS in overweight males. We also performed a multivariable regression analysis to examine factors affecting cleansing in the right colon.ResultsA total of 1307 patients were included. Pooled N2D showed significantly improved rates of adequate-level cleansing in the right colon compared with 2LPEG (97.5% [504/517] vs. 94.6% [246/260]; p = 0.020) and OSS (97.5% [504/517] vs. 93.8% [244/260]; p = 0.006). In MORA, the rate of adequate right colon cleansing did not significantly differ between N1D and 2LPEG (95.2% [257/270] vs. 94.6% [246/260]; p = 0.383). The rate of right colon high-quality cleansing was significantly improved with N2D or N1D vs. 2LPEG (p < 0.001 for both), and was numerically higher with N2D versus OSS (p = 0.11). In overweight males, NER1006 delivered numerically higher adequate (p = 0.398) and superior high-quality (p = 0.024) cleansing rates versus 2LPEG/OSS. Multivariable regression analysis showed NER1006 was associated with adequate and high-quality cleansing (p = 0.031 and p < 0.001), while time between preparation and colonoscopy was negatively associated (p = 0.034 and p = 0.006).ConclusionsNER1006 delivered improved rates of adequate and high-quality right colon cleansing compared with 2LPEG and OSS. The increased rate of high-quality cleansing with NER1006 versus its comparators was also seen in overweight males.

P233 Efficacy and safety of oral sulfate tablet for the bowel preparation in patients with inflammatory bowel disease: multicenter randomized controlled study

Abstract Background Although high and low volume polyethylene glycol(PEG) bowel preparations are recommended for patients with inflammatory bowel disease(IBD) before colonoscopy, sometime it is limited due to poor compliance. So, studies regarding novel low volume preparations in IBD are need, but, there is limited data. We aimed to evaluated the safety, tolerability and efficacy of oral sulfate tablet (OST) by comparison with 2L PEG and ascorbate (PEG/Asc) in patients with IBD. Methods One hundred ten patients with IBD were enrolled in this single-blind, multicenter, non-inferiority study. Patients were assigned either 2L PEG/Asc or OST to be administered in a split-dose regimen. OST patients were administered 14 tablets with more than 1L of free water in the evening, and the following morning. Colonoscopies were performed by blinded investigators. The primary efficacy endpoint was successful bowel cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded endoscopist in each hospital. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Flare up of IBD symptoms and mucosa change associated with preparation were also evaluated. Tolerability, in terms of taste and degree of resistance to drink was assessed with VAS score by interview before colnoscopy. Safety was assessed by spontaneously reported adverse events, solicited ratings of expected prep symptoms, and laboratory testing. Results The cleansing score at all the segment was significantly higher in OST group. A high rate of cleansing success was seen with OST (98.1%), which was noninferior to 2L PEG/Asc (98.1%). Proportion of patients with bubble score 0 was significantly higher in OST than 2L PEPG/Asc group (94.5% vs. 50.0%, p&amp;lt;0.001). Satisfaction, in terms of easiness to drink (8.2 ± 1.6 vs. 6.0 ± 2.2, p&amp;lt;0.001) and taste(7.0 ± 2.8 vs. 5.4 ± 2.4, p=0.002) was significantly higher in OST group. More patients in OST group (94.5%) wanted to repeat the same preparation next colonoscopy. There was no significant difference in the development of vomiting and bloating between group. Aphthous ulcers were noted in the same number of patients in both group and symptom flare up were noted in 2 cases of OST group (p=1.000). No clinically significant differences were seen between preps for renal function and serum electrolyte. Conclusion Oral sulfate tablets achieved a high level of cleansing comparable with 2L PEG/Asc in patients with IBD. The risk of mucosal change or symptom relapse were not higher, on the other hand the degree of satisfaction was higher than 2L PEG/Asc. OST split method could be considered as one of the preparation method for patients with inactive IBD.

1 L- versus 2 L-polyethylene glycol with ascorbic acid for bowel preparation in elderly patients: a randomized multicenter study.

1 L-polyethylene glycol (PEG)/ascorbic acid (Asc) was developed to reduce the required oral preparation volume through increasing osmotic load through containing a greater quantity of ascorbate components. We aimed to compare the efficacy, tolerability, and safety of a split-dosing regimen of 1 L-PEG/Asc versus 2 L-PEG/Asc in elderly patients undergoing scheduled colonoscopy. This was a prospective, non-inferiority, randomized, investigator-blinded multicenter study conducted in Korea between July 2019 and December 2020. Patients aged between 65 and 85years were randomized at a ratio of 1:1 to either the 1 L-PEG/Asc or 2 L-PEG/Asc group. The efficacy of the bowel preparation was evaluated using the Harefield Cleansing Scale (HCS) and the Boston Bowel Preparation Scale (BBPS). A total of 202 patients were analyzed. Successful overall bowel preparation was similar between the 1 L-PEG/Asc and 2 L-PEG/Asc groups based on HCS (95.1% vs. 93.1%, P = 0.528) and BBPS (93.1% vs. 90.0%, P = 0.422). The perfect overall bowel preparation rate in the 1 L-PEG/Asc group was higher than that in the 2 L-PEG/Asc group (HCS, 40.2% vs. 25.0%, P = 0.021; BBPS, 80.4% vs. 68.0%, P = 0.044). There were more high-quality bowel preparations for the right colon in the 1 L-PEG/Asc group (HCS, 46.1% vs. 30.0%, P = 0.019; BBPS, 83.3% vs. 70.0%, P = 0.025). The adenoma detection rate (47.1% vs. 49.0%, P = 0.782), rate of adverse events (25.5% vs. 23.0%, P = 0.680), shifts in laboratory results, and tolerability were comparable between the groups. 1 L-PEG/Asc was as effective, safe, and tolerable as 2 L-PEG/Asc in elderly patients with comorbidities.

Bowel-cleansing efficacy of the 1L polyethylene glycol-based bowel preparation NER1006 (PLENVU) in patient subgroups in two phase III trials.

Background:Adequate bowel preparation prior to colonoscopy is essential for visualization of the colonic mucosa to maximize adenoma and polyp detection. The risk of inadequate bowel cleansing is heightened if the patient is older, male, overweight, and has comorbidities, such as diabetes. This post hoc analysis of the combined MORA and NOCT clinical trials explores the efficacy of evening/morning split-dose regimens of NER1006 (PLENVU®, Norgine Ltd), a 1-liter polyethylene glycol (PEG) bowel preparation, to evaluate its bowel-cleansing efficacy in patients at risk for inadequate cleansing.Methods:Patients requiring colonoscopy were randomized to receive evening/morning split-dosing of either NER1006, 2-liter (2L) PEG and ascorbate, or oral sulfate solution (OSS). Bowel-cleansing efficacy was assessed by treatment-blinded central readers using the validated Harefield Cleansing Scale (HCS).Results:Split-dose NER1006 was associated with high levels of cleansing, ranging between 87.0% and 94.0% across all patient subtypes (n = 551), including patients with obesity or diabetes. However, patients aged >65 years and <45 years showed significantly greater rates of successful cleansing than patients aged 45–65 years (94.0% versus 94.2% versus 87.0%, p = 0.002). The high-risk patient subgroup, which included obese males aged ⩾60 years, had significantly improved overall and high-quality bowel-cleansing success rates of 100% (33/33) and 72.7% (27/33) on the HCS with NER1006, compared with 86.7% (26/30) and 50% (15/30) with the comparator solutions (p = 0.015 and p = 0.033, respectively). In this high-risk subgroup, adenoma detection was greater per patient receiving NER1006 versus the comparator group (1.82 versus 0.93, p = 0.041). NER1006 was the only treatment that enabled the detection of patients with ⩾5 adenomas [9.1% (3/33) versus 0/30, p = 0.047].Conclusion:NER1006 effectively cleansed a broad range of patients and offered superior bowel cleansing versus 2LPEG/OSS in patients at increased risk of colorectal cancer. Future research should establish whether more effective cleansing also enables improved adenoma detection.Plain language summaryA low-volume bowel preparation solution to better detect lesions associated with colorectal cancer during colonoscopyColorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the world. Obese men over the age of 65 years are at particularly increased risk of developing CRC. If the changes in their large intestine (colon) could be seen more clearly during a colonoscopy (where a small camera is inserted via the anus to examine the bowels from the inside), patients who need treatment would be diagnosed earlier, thus improving their chances of survival. In this paper we discuss the use of a bowel preparation solution that is more convenient for patients (less to drink) but also cleans bowels more effectively, meaning more lesions are detected than when other solutions are used. This improved cleansing, and thus better visualization, occurred in a range of patients, including those at higher risk of CRC, such as older, overweight men.

Bowel preparation for colonoscopy: is diet restriction necessary?

Background: Bowel preparation is essential for quality colonoscopy. Although most bowel preparation regimens recommend dietary restriction for 24 to 48 hours before the procedure, the evidence for this is poor. This study aimed to investigate whether dietary restriction during bowel preparation improves the quality of colonoscopy. Methods: A prospective, randomised controlled pilot study in which the dietary restriction (DR) group (control) was instructed not to ingest high fibre foods for 48 hours prior to the use of a polyethylene glycol (PEG) bowel preparation. The non-dietary restriction (NDR) group were given no dietary instruction but received instructions for the use of the PEG-based preparation. On the day of colonoscopy, the quality of the bowel effluent was assessed, and additional preparation given as necessary. The primary endpoint was quality of bowel cleansing using the Harefield Cleansing Scale during colonoscopy. The secondary endpoints were the need for additional bowel preparation and the quantity of additional bowel preparation given prior to endoscopy. Data were analysed on an intention to treat basis. Results: Twenty-three participants were randomised to the intervention group and thirty-four to the control group. Patient demographics were similar in both groups. Dietary restriction did not influence the success rate of bowel preparation: 97% successful bowel preparation in the DR group, vs 91% successful bowel preparation in the NDR group (p = 0.559). Additional bowel preparation requirement were similar in both groups: 35% in the DR group vs 39% in the NDR group (p = 0.768). Mean amount of additional bowel preparation required was similar: 560 ml in the DR group vs 460 ml in the NDR group (p = 0.633). Conclusion: The quality of bowel preparation was comparable in patients with and without dietary restrictions prior to colonoscopy. Non-restrictive diets prior to bowel preparation should be considered to increase compliance. The sample size of this pilot study prohibited definite statistical conclusions but demonstrated this to be a reasonable methodology for a larger study.

P037 Efficacy and Safety of 1-L NER1006 Bowel Preparation in Patients with Inflammatory Bowel Disease: Analysis of 2 Phase 3 Studies.

BACKGROUND: NER1006 (Plenvu®, Salix Pharmaceuticals, Bridgewater, NJ), a 1-L polyethylene glycol (PEG)-based bowel preparation, is indicated in the United States for colon cleansing in preparation for colonoscopy in adults. Colonoscopy is an important tool for the diagnosis, management, and colon cancer screening/surveillance of patients with inflammatory bowel disease (IBD), and adequate bowel preparation is critical for effective performance of colonoscopy. The current data analysis was conducted to assess the efficacy and safety of 1-L NER1006 in an adult population who received this bowel preparation prior to colonoscopy, sub-grouped by IBD diagnosis. METHODS: NER1006 data were pooled from two phase 3, randomized studies (NOCT and MORA) of patients (aged 18-85 y) undergoing colonoscopy. Patients with ongoing severe, acute IBD were excluded. Patients received NER1006 as a 2-day evening/morning or 1-day morning/morning split-dosing regimen. Total NER1006 volume requirements were 64 oz plus clear liquids ad libitum. Colon cleansing was assessed by treatment-blinded central readers. The 2 primary endpoints of the studies were overall bowel cleansing success rate and ascending colon/cecum high-quality cleansing rate. Overall cleansing success was defined as Harefield Cleansing Scale (HCS) grade A/B (score = 3/4 [ie, clear liquid/empty and clean] in all 5 colonic segments or score = 2 [ie, brown liquid/removable semi-solid stools] for ≥1 segment with score 3/4 for remaining segments). High-quality cleansing in the ascending colon/cecum was defined as an HCS score = 3/4. Efficacy analyses were conducted in the modified full analysis set population, defined as all randomly assigned patients excluding those who failed to meet entry criteria post-randomization and who also did not receive any study drug. Safety was assessed in all randomly assigned patients in whom it could not be ruled out that they received ≥1 dose of NER1006 (per patient diary). Safety was assessed through 7 ± 1 days post-colonoscopy. Safety assessments included adverse event (AE) reporting, clinical laboratory evaluations, vital sign measurements, and physical examinations; urinalysis and electrocardiogram were performed at screening and on the day of colonoscopy. RESULTS: A total of 13 and 813 patients who did and did not have a medical history of IBD, respectively, were included in the pooled efficacy analysis, with a majority in each group receiving a 2-day split-dose regimen (61.5% and 66.8%, respectively). Overall cleansing success was achieved in 92.3% (12/13) of patients with IBD and 88.7% (721/813) of patients without IBD. High-quality cleansing of the ascending colon/cecum was reported in 38.5% (5/13) of patients with IBD and 33.7% (274/813) of patients without IBD. Based on post-colonoscopy diagnosis, safety was analyzed for 12 patients with IBD. Only 1 patient with IBD (NER1006 1-day split-dose group) experienced an AE (mild vomiting), and it did not result in study discontinuation. CONCLUSION: Data support the overall efficacy and safety profile of 1-L NER1006 as a bowel preparation in patients with IBD. Further studies in patients with IBD are warranted given the essential nature of careful mucosal evaluation for dysplasia surveillance and lesion detection in this patient population. NOTE: Plenvu® is a registered trademark of the Norgine group of companies used under license.

S0237 One Liter Polyethylene Glycol-Based NER1006 Is Efficacious as a Bowel Preparation for Colonoscopy in Patients With or Without Diabetes Mellitus: A Pooled Analysis of 2 Randomized, Phase 3 Studies

INTRODUCTION: Diabetes mellitus (DM) has been found to be an independent risk factor for inadequate bowel preparation for colonoscopy. NER1006, a 1 L polyethylene glycol (PEG)-based bowel preparation, was approved in the US in 2018 for colon cleansing in preparation for colonoscopy in adults. The aim of this study was to compare the efficacy of NER1006 bowel preparation in adults with DM compared with those without DM. METHODS: A pooled post hoc analysis was conducted of two phase 3 studies (NOCT and MORA) of adults undergoing colonoscopy randomized to receive evening/morning split-dose regimen of NER1006, excluding those failing to meet entry criteria post-randomization and also not receiving NER1006. Overall colon cleansing success rates were assessed using the Boston Bowel Preparation Scale (BBPS; success defined as overall score ≥6 with score ≥2 in each segment [right, transverse, and left colon]) or Harefield Cleansing Scale (HCS; success defined as all 5 colonic segments scored 3 [clear liquid] or 4 [empty and clean] or ≥1 segment scored 2 [brown liquid/fully removable semi-solid stools] and other segments scored 3 or 4 [ie, good/excellent]). Good/excellent cleansing quality (colon segments free of stool; score 3 or 4) for each segment using the HCS and overall colon adenoma detection rate (ADR; number of patients with ≥1 adenoma divided by total population) was also determined. P values were calculated using a 2-sided Fisher’s exact test. RESULTS: 47 patients with type 1 DM or type 2 DM (reported as part of medical history) and 504 patients without DM were included. Some numeric differences in demographics in DM versus non-DM groups were observed (eg, male, 55.3% vs 45.4%; mean age, 63.6 y vs 56.4 y; weight, 89.7 kg vs 80.3 kg). There was no significant difference in the NER1006 overall colon cleansing success rate in patients with DM compared with those without DM using the BBPS (78.7% vs 87.3%; P = 0.12) or HCS (78.7% vs 89.5%; P = 0.05). Good/excellent cleansing quality in each colonic segment was achieved in a similar percentage of patients with DM or without DM (Figure 1). The overall ADR was significantly higher in patients with DM (51.1%) versus patients without DM (28.2%; P = 0.002), but ADR was comparable for the ascending colon (19.1% vs 12.3%; P = 0.18). Limitations include the small number of patients and lack of stratification by type of DM.Figure 1.: Patients with excellent or good quality bowel cleansing (HCS), by colonic segmentCONCLUSION: These data support that 1 L PEG-based NER1006 is efficacious as a bowel preparation in adults with DM undergoing colonoscopy.

Improved detection of colorectal adenomas by high-quality colon cleansing.

Background and study aims Reliable adenoma detection requires “adequate” bowel preparation. The adenoma detection rate (ADR) was assessed in patients with high-quality (stool-free) cleansing versus adequate cleansing. Patients and methods This study was a post-hoc combined analysis of three randomized trials individually powered for cleansing quality assessment. Treatment-independent ADR was assessed versus colon cleansing quality by central readers using the Harefield Cleansing Scale (HCS) and the Boston Bowel Preparation Scale (BBPS). The number needed to treat (NNT) to find an additional patient with at least one adenoma was calculated for high-quality versus adequate-quality cleansing. Results A total of 1749 patients were included. ADR increased with high-quality versus adequate-quality cleansing: HCS grade A versus B, 39 % (94/242) versus 27 % (336/1229); NNT = 8.7; P < 0.001. ADR also increased with high-quality versus uniform adequate segmental cleansing scores: HCS grade A versus uniform segmental scores 2, 39 % (94/242) versus 26 % (97/379); NNT = 7.5; P < 0.001. ADR increased with top-quality versus adequate segmental cleansing scores: HCS uniform segmental scores 4 versus 2, 54 % (21/39) versus 26 % (97/379); NNT = 3.6; P < 0.001. ADR increased with BBPS 9 versus 6, 43 % (71/166) versus 26 % (247/950); NNT = 6.0; P < 0.001. Right colon ADR increased with top-quality versus adequate cleansing: HCS 4 versus 2, 20 % (25/122) versus 11 % (121/1117); NNT = 10.4; P < 0.001 and BBPS 3 versus 2, 15 % (42/284) versus 11 % (130/1192); NNT = 25.8; P = 0.033. Conclusions High-quality colon cleansing improves adenoma detection, and it should be a priority for bowel preparations for colonoscopy.

High-quality colon cleansing and multiple neoplasia detection with 1L NER1006 versus mid-volume options: Post hoc analysis of phase 3 clinical trials.

Background and study aims Multiple neoplasia increase the risk of colorectal cancer. High-quality cleansing may improve adenoma detection. We assessed whether a new bowel preparation can improve colon cleansing and multiple lesion detection. Patients and methods This post hoc analysis of two randomized clinical trials in Europe and the US assessed the per study and combined cleansing efficacy of overnight split dosing with (preparation + clear fluids) 1 + 1 L polyethylene glycol (PEG) NER1006 versus 2 + 1 L PEG + ascorbate (2LPEG) or 1 + 2 L oral sulfate solution (OSS) combined. Treatment-blinded central readers assessed cleansing quality using the Harefield Cleansing Scale (HCS). Patients with full segmental scoring were included. HCS segmental scores 0–4 (high-quality = HCS 3–4) were analyzed for NER1006 versus 2LPEG/OSS. Mean number of polyps or adenomas per patient (MPP/MAP) was calculated for treatments in patients with at least one polyp or adenoma. Results In 1037 patients, NER1006 attained a greater rate of HCS 3 scores (29 % vs. 20 %; P < 0.001) and HCS 4 scores (20 % vs. 17 %; P = 0.007) versus 2LPEG/OSS. More polyps (678 versus 585) and adenomas (397 versus 331) were detected with NER1006 (N = 517) versus 2LPEG/OSS (N = 520). In all neoplasia-positive patients, with increasing minimal per-patient neoplasia multiplicity from 1 to 10, NER1006 numerically improved MPP (difference ± SE: 0.48 ± 0.24 to 3.89 ± 3.37) and MAP (0.47 ± 0.26 to 7.50 ± 9.00) versus 2LPEG/OSS. Conclusions Low-volume NER1006 enhances high-quality cleansing versus medium-volume 2LPEG or OSS, individually and when combined. NER1006 may consequently facilitate the detection of multiple neoplasia in patients.

313 1 L NER1006 Improves High-Quality Colon Cleansing and Mean Polyp Detection versus Oral Sulfate Solution and 2 L Polyethylene Glycol Plus Ascorbate

INTRODUCTION: Interval cancers may occur due to missed neoplasia during colonoscopy. ‘Adequate’ cleansing quality permits stool presence in the colon, however high-quality (stool-free) cleansing is now known to improve polyp detection. The 1 L polyethylene glycol (PEG) NER1006 improves high-quality colon cleansing, but whether it primarily reduces stool or liquid is unknown. We characterized the segmental high-quality cleansing with NER1006 versus two comparators, and its effect on mean polyp detection per patient. METHODS: A post hoc analysis of two similarly designed phase 3 clinical trials NOCT and MORA examined overnight split-dosing regimens. NER1006 was compared with oral sulfate solution (OSS; NOCT) and 2 L polyethylene glycol + ascorbate (2LPEG; MORA). Treatment-blinded central readers assessed colon cleansing quality using the Harefield Cleansing Scale (HCS) with segmental scores 0-1 (failures; irremovable stool), 2 (adequate; removable stool), 3 (high-quality; clear liquid) or 4 (high-quality; liquid-free). Site endoscopists detected polyps. Patients with full segmental scoring were included. The segmental scores distribution and mean number of polyps per patient (MPP; in patients with at least 1 to 10 polyps) were analysed per treatment group. MPP was also assessed in pooled NER1006 versus pooled OSS and 2LPEG. One-sided t-tests assessed potential differences between groups. RESULTS: Totally 1037/1103 patients were included (94% primary analysis set = 5185 segments). NER1006 attained more stool-free segments (HCS 3) than OSS (30% [388/1275] vs 25% [331/1300]; P = 0.002) [Figure 1] or 2LPEG (28% [368/1310] vs 15% [191/1300]; P&lt; 0.001) [Figure 2]. NER1006 attained more liquid-free segments (HCS 4) than 2LPEG (22% [285/1310] vs 17% [220/1300]; P = 0.001), and less stool-containing segments (HCS 2) than OSS (48% [612/1275] vs 53% [687/1300]; P = 0.007 or 2LPEG (49% [641/1310] vs 66% [854/1300]; P &lt; 0.001). Pooled NER1006 showed a higher MPP than pooled OSS and 2LPEG for at least 1 (2.8 vs 2.3; P = 0.036), 2 (4.4 vs 3.5; P = 0.020), 3 (5.7 vs 4.5; P = 0.033), 4 (7.3 vs 5.8; P = 0.049), 5 (9.7 vs 6.8; P = 0.017) and 6 polyps per patient (10.9 vs 7.5; P = 0.020) [Figure 3]. In all other patients NER1006 had a numerically higher MPP per trial and when pooled. CONCLUSION: Finding multiple polyps in a patient is difficult. NER1006 improves high-quality cleansing over OSS or 2LPEG primarily by delivering more stool-free segments. This improved high-quality cleansing enables detection of more polyps per patient.

314 In Patients With an Overall Cleansing Success the 1L Polyethylene Glycol NER1006 Achieves More High-Quality Cleansed Segments per Patient Than Three Standard Bowel Preparations

INTRODUCTION: In pre-colonoscopy colon cleansing, the presence of removable stool is currently considered a success for reliable adenoma detection. The phase 3 trials of 1L polyethylene glycol (PEG) NER1006 (trials DAYB, MORA and NOCT) are the largest to date joint prospective study on colon cleansing quality. Split dosing with NER1006 achieved a higher or at least as high cleansing success as sodium picosulfate/magnesium citrate (SPMC), 2L PEG + ascorbate (2LPEG), or oral sulfate solution (OSS). NER1006 also improves high-quality (HQ) cleansing in whole treatment groups, but patient level benefits are unclear. METHODS: This post hoc analysis of DAYB, MORA and NOCT examined if NER1006 increases the number of HQ segments per patient vs SPMC, 2LPEG or OSS, and if that could improve the adenoma detection rate (ADR) or mean number of adenomas per patient (MAP). Treatment-blinded central readers used the Harefield Cleansing Scale (HCS) to assess cleansing quality. Site endoscopists detected polyps; adenomas were confirmed by histology. Patients with full HCS scoring and adenoma counts were included. In overall cleansing successes, (HCS Grades A-B; have segments with removable stool), the number of HQ segments (HCS scores 3-4; stool-free) per patient was assessed. One-sided t-tests compared treatments. Per-patient regression analyses assessed whether HQ segments per patient improves ADR (logistic; LogR) or MAP (linear; LinR), in all patients and in cleansing successes. Odds ratios or average increments are presented with 95% CI. Trend curves were plotted with data points for group means ± SD. RESULTS: A total of 1749 patients were included, 1471 (84%) with overall cleansing success (Figure 1). In cleansing successes, NER1006 achieved more HQ segments per patient than SPMC (1.13 ± 1.29 vs 0.76 ± 1.07; P = 0.005), 2LPEG: (2.52 ± 1.76 and 2.65 ± 1.81 vs 1.65 ± 1.71; P &lt; 0.001 for both) and OSS (2.61 ± 1.8 vs 2.30 ± 1.81; P = 0.032). More HQ segments per patient showed positive odds for ADR in all (OR 1.09 [1.03-1.16]; Ptrend = 0.003) and successfully cleansed patients (OR 1.11 [1.04-1.18]; Ptrend = 0.001) [Figure 2]. With LinR, more HQ segments per patient increased MAP in all (average increment 0.05 [0.01-0.09]; Ptrend = 0.012) and successfully cleansed patients (average increment 0.05 [0.01-0.10]; Ptrend = 0.025) [Figure 3]. CONCLUSION: NER1006 delivered more HQ segments per patient than SPMC, 2LPEG or OSS. More HQ segments per patient may increase ADR and MAP and thus protect patients against colorectal cancer.

144 Efficacy and Safety of NER1006 Versus Standard Bowel Preparations: A Meta-Analysis of Randomized Phase 3 Clinical Trials

INTRODUCTION: The efficacy of bowel cleansing is essential for a quality colonoscopy, especially in the setting of colorectal cancer screening. Unfortunately, suboptimal bowel preparation is still observed in 25% of procedures. Recently, a very low-volume 1L PEG solution (NER1006) has been introduced on the evidence of three phase 3 randomized controlled trials. We conducted a meta-analysis to explore cleansing success, adenoma detection rate (ADR), and safety profile of NER1006 versus standard bowel preparations. METHODS: PubMed/Medline and Embase were systematically searched through April 2019 by two independent reviewers (M.M. and F.S.M.) for randomized phase 3 clinical trials comparing the effectiveness of NER1006 versus standard bowel preparations. RESULTS: Three RCTs (four arms, 2151 participants) met the inclusion criteria and were included in the meta-analysis (Table 1). The analysis showed a significant higher overall cleansing success for patients receiving NER1006 compared with standard preparations both using the Harefield Cleansing Scale (HCS) (OR 1.29; 95% CI 1.02–1.61; P = 0.031, I2 = 0%, 2151 participants) and the Boston Bowel Preparation Scale (BBPS) (OR 1.43; 95% CI 1.15–1.78; P = 0.001, I2 = 0%, 2151 participants) (Figure 1a,b), as well as a significant greater high-quality cleansing of the right colon both when assessed with the HCS (OR 2.26; 95% CI 1.44–3.54; P &lt; 0.001, I2 = 70%, 2151 participants) and with the BBPS (OR 1.74; 95% CI 1.09–2.79; P = 0.021, I2 = 66%, 2151 participants) (Figure 1c,d). The pooled estimate of the NER1006 effect on ADR showed no significant difference in terms of overall ADR (OR 1.03; 95% CI 0.85–1.24; P = 0.773, I2 = 0%, 2151 participants), and a higher, although not significant, ADR of the right colon (OR 1.24; 95% CI 0.85–1.79; P = 0.262, I2 = 38%, 2151 participants) (Figure 2a,b). When considering the impact of NER1006 on mild to moderate treatment-emergent adverse events (TEAEs), we observed a significant pooled estimate of number of TEAEs (OR 2.25; 95% CI 1.81–2.80; P &lt; 0.001, I2 = 0%, 2060 participants) and of patients with TEAEs (OR 1.80; 95% CI 1.36–2.38; P &lt; 0.001, I2 = 0%, 2060 participants) (Figure 2c,d). No serious adverse events occurred. CONCLUSION: Compared with standard bowel preparations, NER1006 showed a higher overall cleansing success, a greater high-quality cleansing of the right colon and a higher, although not significant, ADR of the right colon. NER1006 showed a higher incidence of mild to moderate TEAEs, in the absence of serious adverse events.

Improved high-quality colon cleansing with 1L NER1006 versus 2L polyethylene glycol + ascorbate or oral sulfate solution

Background & aimsColonoscopy requires bowel cleansing for gut mucosa visualization; high-quality cleansing facilitates lesion detection. NER1006 is a 1L polyethylene glycol (PEG) bowel preparation. This post hoc analysis of two randomized trials investigated cleansing efficacy assessed, as in clinical practice, by site endoscopists. MethodsPatients received NER1006, 2L PEG + ascorbate (2LPEG), or oral sulfate solution (OSS) as a 2-day evening/morning regimen (N2D) or NER1006 morning-only dosing (N1D). Treatment-blinded site endoscopists assessed cleansing using the Harefield Cleansing Scale (HCS). Analyses were conducted in a modified full analysis set, including (mFAS; n = 1378) or excluding (mFAS2; n = 1319) imputed failures, and in patients with 100% treatment adherence (mFAS100; n = 1047). Overall cleansing success (HCS grade A/B), overall high-quality cleansing (HCS grade A), and high-quality segments (HCS 3–4) per treatment population were analyzed. ResultsOverall cleansing success was higher with N2D than 2LPEG (92.7–97.5% vs. 87.9–93.0%), and more patients had overall high-quality cleansing with N2D and N1D than 2LPEG (68.0–72.1% and 64.0–68.4% vs. 50.7–56.0%). Without imputed failures, N2D delivered more overall high-quality cleansing than OSS (74.5–77.3% vs. 67.8–69.8%). More high-quality segments were demonstrated with N2D and N1D versus 2 LPEG (82.5–87.1% and 79.4–84.4% vs. 70.4–76.3%) and with N2D versus OSS (82.7–89.5% vs. 78.1–84.4%). ConclusionWhen assessed by site endoscopists, NER1006 delivers greater high-quality cleansing than 2LPEG or OSS.

Novel 1\u2009L polyethylene glycol-based bowel preparation (NER1006): proof of concept assessment versus standard 2\u2009L polyethylene glycol with ascorbate \u2013 a randomized, parallel group, phase 2, colonoscopist-blinded trial

BackgroundColonoscopy requires colon cleansing. For this, many polyethylene glycol (PEG)-based preparations still require a high preparation-volume intake. Using an increased osmotic load with ascorbate (Asc), five new low-volume PEG-based bowel preparations (LVPEG) were tested for clinical proof of concept.MethodsThis two-part, open-label study examined preparation-volumes of 1–1.25 L and total required fluid volumes of 2–3 L. Part 1, in healthy volunteers, used mean cumulative 24-h stool weight (target > 2750 g) to identify a lead candidate. Part 2 was endoscopist-blinded: patients undergoing screening colonoscopy were randomized before treatment with the selected lead, one of two variants of it, or the control 2 L PEG + Asc. Two primary endpoints were used for proof of concept demonstration: mean 24-h stool weight and bowel cleansing success (Harefield Cleansing Scale).ResultsA total of 120 subjects (30 per group) were enrolled/randomized 1:1:1:1 (max 40:60 gender ratio) per completed Part. In Part 1, LVPEG-3 achieved the largest mean stool weight (3399 g: P < 0.0001 vs target) and was selected for Part 2. In Part 2, stool weights exceeded the target, notably for LVPEG-4 (3215 g: P < 0.001), which achieved 100% cleansing success after a total required fluid intake of 2 L. The control achieved 90% cleansing success. Adverse events were few, gastrointestinal in nature and similar between groups.ConclusionsLVPEG-4 achieved a clinically useful combination of cleansing, safety/tolerability and low consumption volume: 1 L preparation + 1 L required additional fluid. Named NER1006, LVPEG-4 demonstrated clinical proof of concept and warrants further investigation.Trial registrationOctober 2012.Identifier: NCT01714466. EudraCT: 2012–003052-37The trial was prospectively registered.