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

Abstract

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 summary A low-volume bowel preparation solution to better detect lesions associated with colorectal cancer during colonoscopy Colorectal 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.

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

“…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.…”

“…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.…”

“…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 ].…”

Factors affecting the quality of bowel preparation for colonoscopy in hard-to-prepare patients: Evidence from the literature

“…Patients were randomized to receive split-dosing of either NER1006, 2-L PEG-ASC, or OSS in a recent (2021) two phases III Spanish trials[ 77 ]. Split-dose NER1006 (1-L-PEG-ASC) was associated with high levels of cleansing, ranging from 87% to 94% in a total of 551 patients, including those who were obese or diabetic.…”

Effects on BBPS score with bowel preparation time and dosage

“…[ 9 ] Adequate bowel preparation prior to colonoscopy is essential for visualization of the colonic mucosa. [ 10 ] The higher the cleanliness of the bowel preparation, the clearer the lesions will be displayed under the colonoscopy. Therefore, optimization of bowel preparation can improve the quality of colonoscopy.…”