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

BACKGROUND: Colonoscopy 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. METHODS: This 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). RESULTS: A 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. CONCLUSIONS: LVPEG-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 REGISTRATION: October 2012. Identifier: NCT01714466 . EudraCT: 2012-003052-37 The trial was prospectively registered.

Validation of the Harefield Cleansing Scale: a tool for the evaluation of bowel cleansing quality in both research and clinical practice.

BACKGROUND: Variations in bowel cleansing quality before colonoscopy can cause confounding of results within clinical trials and inappropriate treatment decisions in clinical practice. A new tool-the Harefield Cleaning Scale-has been developed, which addresses the limitations of existing scales. OBJECTIVE: Validation exercise for the new cleansing scale. DESIGN: Retrospective validation study. SETTING: Various colonoscopy units in France. PATIENTS: Patients who had a total of 337 colonoscopies recorded. INTERVENTION: Video-recorded colonoscopy. MAIN OUTCOME MEASUREMENTS: Comparisons of 2 scoring systems to assess direct correlation, interrater reliability, internal consistency, and test-retest reliability, based on assessment of video recordings from 337 colonoscopies. RESULTS: Correlation analysis for expert scores by using the 2 scales yielded a Spearman correlation coefficient of 0.833. Similarly, the comparison of the segmental sum score revealed a Spearman correlation coefficient of -0.778. Cross-tabulation for successful colon cleansing was 92.88% versus unsuccessful colon cleansing in 7.12%. Reliability assessment indicated an acceptable internal consistency with a Cronbach alpha coefficient of 0.81. Test-retest reliability demonstrated an overall agreement of 0.639 (kappa statistic). Receiver operating characteristic analysis versus Aronchick Scale scores yielded an area under the curve of 0.945, with sensitivity of 99% and specificity of 83% at the optimum score cut-off point. LIMITATIONS: Test-retest reliability was assessed by using a different patient population to the other measures. There were insufficient patient numbers to assess performance by using adenoma detection rate. CONCLUSION: This validation analysis has demonstrated that the Harefield Cleansing Scale is a robust, reliable, and consistent tool that has the potential to improve the effective standardization of bowel preparation assessment in both clinical and research practice.

Impact of the quality of bowel cleansing on the efficacy of colonic cancer screening: a prospective, randomized, blinded study.

OBJECTIVES: Efficacy of two low volume bowel cleansing preparations, polyethylene glycol plus ascorbate (PEG + Asc) and sodium picosulfate/magnesium citrate (NaPic/MgCit), were compared for polyp and adenoma detection rate (PDR and ADR) and overall cleansing ability. Primary endpoint was PDR (the number of patients with ≥ 1 polypoid or flat lesion recorded by the colonoscopist). METHODS: Diagnostic, surveillance or screening colonoscopy patients were enrolled into this investigator-blinded, multi-center Phase IV study and randomized 1:1 to receive PEG + Asc (administered the evening before and the morning of colonoscopy, per label) or NaPic/MgCit (administered in the morning and afternoon the day before colonoscopy, per label). The blinded colonoscopist documented any lesion and assessed cleansing quality (Harefield Cleansing Scale). RESULTS: Of 394 patients who completed the study, 393 (PEG + Asc, N = 200; NaPic/MgCit, N = 193) had a colonoscopy. Overall PDR for PEG+Asc versus NaPic/MgCit was 51.5% versus 44.0%, p = 0.139. PDR and ADR on the right side of the bowel were significantly higher with PEG + Asc versus NaPic/MgCit (PDR: 56[28.0%] versus 32[16.6%], p = 0.007; ADR: 42[21.0%] versus 23[11.9%], p = 0.015), as was detection of flat lesions (43[21.5%] versus 25[13.0%], p = 0.025). Cleansing quality was better with PEG + Asc than NaPic/MgCit (98.5% versus 57.5% considered successful cleansing). Overall, there were 132 treatment-emergent adverse events (93 versus 39 for PEG+Asc and NaPic/MgCit, respectively). These were mainly mild abdominal symptoms, all of which were reported for higher proportions of patients in the PEG+Asc than NaPic/MgCit group. Twice as many patients in the NaPic/MgCit versus the PEG + Asc group reported tolerance of cleansing solution as 'very good'. CONCLUSIONS: Compared with NaPic/MgCit, PEG + Asc may be more efficacious for overall cleansing ability, and subsequent detection of right-sided and flat lesions. This is likely attributable to the different administration schedules of the two bowel cleansing preparations, which may positively impact the detection and prevention of colorectal cancer, thereby improving mortality rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT01689792.

A low-volume polyethylene glycol plus ascorbate solution for bowel cleansing prior to colonoscopy: the NORMO randomised clinical trial.

BACKGROUND: Patient acceptability of the preparation is a key factor in the success of colonoscopy, yet standard polyethylene glycol solutions are poorly tolerated owing to their high volume (4L) and low palatability. This study compared the efficacy, safety and acceptability of a 2L polyethylene glycol+ascorbate solution with a standard 4-L polyethylene glycol solution. METHODS: Adults referred for colonoscopy were randomised to 2-L polyethylene glycol+ascorbate (n=202) or 4-L polyethylene glycol solution (n=198). Colon cleansing success was assessed using the Harefield Cleansing Scale(©) and the Aronchick scale. Safety and acceptability were also assessed. RESULTS: Successful cleansing was achieved in 94.1% and 90.9% of subjects with the 2-L and 4-L solutions respectively using the Harefield Cleansing Scale(©) and 94.6% and 90.0% using the Aronchick scale (non significant). Despite better acceptability and tolerability, no superiority over the standard 4-L preparation was demonstrated. Fewer treatment-related adverse events were reported with the 2-L solution (80.2% versus 89.9%, p=0.011). More subjects were willing to take the 2L PEG+ascorbate solution again (87% versus 51%, p<0.001), found it easier to drink (80% versus 70%, p=0.025), with a better taste (p=0.01). CONCLUSIONS: Two-litre polyethylene glycol+ascorbate solution, with a similar high degree of cleansing and superior acceptability and tolerability, presents an alternative to 4-L polyethylene glycol when compliance is an issue.

Meta-analysis: efficacy of small bowel preparation for small bowel video capsule endoscopy.

OBJECTIVE: It is unclear whether small bowel visibility in video capsule endoscopy (VCE) is enhanced by the use of bowel preparation in addition to pre-procedural fasting. The objective of this study was to clarify this issue by means of a systematic review of the literature and meta-analysis. METHODS: Randomised controlled trials comparing the use of laxative bowel preparation with fasting alone were identified using a literature search. Categorical measures of treatment efficacy were extracted from qualifying studies and pooled using random-effects meta-analyses. Primary analysis compared any bowel preparation with fasting alone; subsidiary analyses assessed diagnostic yield and results for each regimen. RESULTS: Eight studies were identified, using either polyethylene glycol (PEG) or sodium phosphate (NaP) based regimens. No qualifying studies were identified using other laxatives. Study quality was sufficiently high to warrant meta-analysis. Use of any form of bowel preparation yielded significantly better visibility than fasting alone (OR = 2.31; 95% CI = 1.46-3.63; p < 0.0001). Similar results were seen for diagnostic yield (OR = 1.88; 95% CI = 1.24-2.84; p = 0.023). When sub-analysed according to the treatment used, PEG-based regimens showed benefit (OR = 3.11; 95% CI = 1.96-4.94; p < 0.0001), while NaP-based regimens yielded no significant difference from fasting alone (OR = 1.32; 95% CI = 0.59-2.96; p < 0.0001). LIMITATIONS: The study did not consider results from retrospective studies, nor those which did not give a categorical measure of efficacy. The impact of prokinetic and other adjunctive treatments was not considered. The results are only relevant to the most commonly used video capsule, as data for newer alternative devices have not yet been published. CONCLUSION: Based on the results of this analysis, the use of bowel preparation alongside fasting is recommended for VCE. PEG-based regimens offer a clear advantage in these patients, while the currently available evidence base does not support the use of NaP. For VCE, lower volume PEG appears to be as efficacious as higher volumes traditionally used for colonoscopy preparation.