This post hoc analysis assessed whether the low-volume PEG-based bowel preparation 1L NER1006 could improve right colon adequate-level and high-quality cleansing success compared with two medium-volume alternatives among patients with complete segmental cleansing data from two randomised controlled trials.
Adequate-level cleansing success is a vital quality metric in colonoscopy [18], and poor bowel preparation can result in missed diagnoses and thereby delay initiation of treatment [19]. Inadequately cleansed patients should, per guideline recommendations, undergo early repeat colonoscopy. Reducing the frequency of early repeat colonoscopies may improve cost effectiveness and also improve patient willingness to undergo the procedure in the future [20,21,22,23,24]. In addition, this inefficiency can lead to delays in attending to other patients on the waiting list.
The right colon is particularly difficult to cleanse to an optimum level for colonoscopy as, following stool clearance from the colon, mucus and chyme that are secreted from the small intestine tend to stick to the caecum and right colon [10]. This increases the risk of missed lesions in the right colon, particularly flat, non-pedunculated lesions and sessile serrated adenomas, which may have a higher malignant potential [7,8,9,10, 25]. In our analysis, pooled data from the evening/morning split-dose NER1006 regimens demonstrated a statistically significant higher rate of right colon adequate-level cleansing versus 2LPEG and OSS individually. Compared with 2LPEG, the low volume of NER1006 is achieved by increasing the ascorbate components of the bowel preparation and including them in the second administered dose [26]. This increases the osmotic activity of the preparation relative to 2LPEG and also enables delivery in a total preparation volume of 1L [14]. This enhanced osmotic activity may contribute to improved cleansing of the right colon, as seen in the original studies and detailed in these post hoc analyses [14,15,16, 27, 29,30,31].
High-quality cleansing, as assessed by the HCS, is associated with numerically improved adenoma detection in the right colon and significantly improved adenoma detection in the overall colon [27]. In its Phase III clinical development programme, NER1006 demonstrated numerically improved high-quality cleansing success rates in the right colon versus all of its comparators and a statistically significant improvement over 2LPEG [14, 15]. In a prospective observational study, a higher proportion of hospitalised patients attained high-quality cleansing in the right colon with NER1006, which was statistically significant, compared with 4LPEG [28]. In the current post hoc analysis, the superior right colon high-quality cleansing success rates obtained with NER1006 in the mFAS2 population are therefore consistent with, and an important clarification of, these previous results.
The superior high-quality cleansing success rate with N2D, when assessed strictly by central readers, is consistent with the previously reported superior overall high-quality cleansing success of N2D versus 2LPEG or OSS as assessed by site endoscopists [29]. Furthermore, the adequate-level and high-quality cleansing rates attained in the right colon in the combined populations of N2D across both the MORA and NOCT trials were superior to those seen in the combined population of patients treated with 2LPEG or OSS (2LPEG/OSS).
Several risk factors contributing to inadequate bowel cleansing have been identified in the literature, and overweight men are regarded as being at high risk [30]. This specific category of patients is also considered to be at increased risk of CRC, with a high prevalence of colorectal adenomas and polyps in this population [31]. In line with previous studies on cleansing efficacy in high-risk patients, in this study, NER1006 effectively delivered comparable levels of right colon adequate cleansing in both overweight males and all other patients [30]. Similar findings were observed in the 2LPEG/OSS group; however, a numerically higher rate was reported in patients treated with NER1006. The superior overall high-quality cleansing efficacy of NER1006 versus 2LPEG/OSS in overweight men and, separately, in obese male patients older than 60 years, has been reported previously [30, 31]. In the current study, NER1006 maintained its high-quality cleansing superiority versus 2LPEG/OSS in the right colon of hard-to-cleanse patients.
This study has several strengths. It is based on two randomised Phase III clinical trials conducted across multiple centres in the USA and Europe to evaluate the cleansing efficacy of the first 1L PEG-based product, NER1006, versus two mid-volume bowel preparations. Importantly, the MORA and NOCT trials were designed with near-identical study protocols, with cleansing assessed by both treatment-blinded endoscopists and central readers using a validated colon-cleansing scale, the HCS. These clinical trials were also the first to be optimised for assessing high-quality cleansing of the right colon as a primary endpoint. The mFAS2, the population set used in this analysis, closely resembles the patient population undergoing colonoscopy in real-world clinics.
Our study has limitations. The major source of limitation is the post hoc analysis. The noticeably lower high-quality cleansing success rates observed in this analysis compared with the adequate-level cleansing rates attained in the right colon are due to the criteria strictly applied by central readers for defining high-quality cleansing on the HCS; the perceived cleansing quality by site endoscopists tends to be higher [13, 29].
In conclusion, in patients who underwent colonoscopy with full segmental scorings using the HCS by treatment-blinded central readers, N2D demonstrated improved adequate and high-quality cleansing of the right colon compared with 2LPEG and OSS. NER1006 successfully delivered comparable high levels of right colon cleansing in overweight males and all other patients. These cleansing benefits of NER1006 are promising, and will hopefully help healthcare practitioners to further enhance the diagnostic and therapeutic efficacy of colonoscopy in the right colon.