Introduction

Two phase III non-inferiority studies (ESTOS [Russia] and EASY [China]) compared split-dose oral sulphate solution (OSS) to 4L polyethylene glycol (PEG) for bowel preparation in adults scheduled for routine colonoscopy. A post-hoc analysis was conducted using pooled data from these studies to provide more information on efficacy and safety overall and in sub-groups of interest.

Aims & Methods

Analyses in intention-to-treat (ITT) were confirmed in the per protocol (PP) population. Sub-analyses were conducted on subgroups of interest (age; gender; body mass index [BMI]; inflammatory bowel disease [IBD] status). A boundary of -15% was used to assess non-inferiority. Primary endpoint: proportion of patients with successful overall preparation (centrally assessed global Boston bowel preparation scale [BBPS] score ≥6). Secondary endpoints: excellent overall preparation (BBPS score ≥8; centralized assessment), mean BBPS score, BBPS score ≥2 by segment, adenomas, polyps and other lesion detection rate, completion and duration of total colonoscopy, investigator satisfaction (Likert score), compliance to bowel preparation administration and safety.

Results

588 patients received OSS (n=294) or PEG (n=294). ITT results confirmed in the PP population are reported. The pooled analysis confirmed non-inferiority of OSS to PEG (successful overall preparation: 93.7% vs 92.1%; Δ 1.6%; 95% CI: −2.6, 5.7). OSS was non-inferior in males (96.2% vs 91.9%) and females (90.9% vs 90.7%), presence (95.9% vs 93.5%) and absence of IBD (95.0% vs 94.2%), BMI ≤25 kg/m² (89.7% vs 94.0%) and age ≤65 years (93.6% vs 90.9%). In patients with BMI >25 kg/m², OSS was superior to PEG (97.0% vs 89.8%, p=0.029). Non-inferiority in patients >65 years was not confirmed (91.6% vs 98.2% p=0.2449). Pooled analyses of secondary endpoints showed higher rates of excellent overall preparation with OSS than with PEG and in segments for most subgroups (Table). Investigator satisfaction was higher with OSS compared with PEG (p=0.0003), as was compliance (92.4% vs 85.1%, p=0.0024). Other secondary endpoints were similar for both treatments. Safety and tolerability were similar for both treatments. Overall, more adverse events (AEs) were experienced in the group with BMI ≤25 than in the group with BMI >25. There was one serious AE considered related to OSS: acute proctitis, which was treated with local mesalamine. The most frequently reported adverse events were non-serious gastrointestinal disorders.

Table. Rates of excellent overall bowel preparation (overall BBPS score ≥8, individual segment score ≥3)

OSS, oral sulfate solution. PEG, polyethylene glycol

Conclusion

Pooled analysis confirmed that OSS is non-inferior to PEG for bowel preparation in adults before colonoscopy. This post-hoc analysis also showed that OSS is superior to 4L PEG in achieving excellent preparation overall and in all colon segments, and is linked to superior compliance and investigator satisfaction in most subgroups with similar safety and tolerability

Disclosure

Evgeny Fedorov, Sergey Kashin and Viktor Veselov were investigators for the ESTOS study, which was sponsered by Ipsen Pharma.
Zong Ye, Wu Yongdong and Zhang Shutian were investigators for the EASY study, which was sponsered by Ipsen Pharma.
Evgeny Fedorov, Sergey Kashin and Viktor Veselov have acted as consultants for Ipsen Pharma.
Anne Kornowski is an employee of Ipsen and Mayoly.
Helene Tribodet is a consultant for Ipsen and Mayoly.

Introduction

Adequate bowel cleansing is essential for colonoscopy quality. A novel 1L polyethylene glycol plus ascorbate (1L PEG+ASC) solution has been recently introduced. Nevertheless, the efficacy of 1L PEG+ASC as compared to that of high-volume bowel preparation in both inpatients and outpatients is still unclear.

Aims & Methods

This single-blinded, non-inferiority RCT aims to compare the efficacy, safety, and tolerability of 1L PEG+ASC versus a high-volume 4L PEG-based preparation in both inpatients and outpatients. The primary endpoint was the overall cleansing success. Secondary endpoints were excellent cleansing and high-quality cleansing of the right colon, as well as lesions detection rate, patient compliance, and safety.

Results

Overall, 478 patients (mean age 59.3 ± 14.9 years) were randomized to 1L PEG+ASC (N = 236) or 4L PEG (N = 242). The 1L PEG+ASC showed higher cleansing success rate as compared to 4L PEG preparation (91.8% vs 83.6%; OR = 2.207; 95% CI: 1.2-4.0; P = 0.01), as well as higher excellent cleansing (39.1% vs 27.7; OR, 1.67; 95% CI: 1.1-2.5; P= 0.001) and high-quality cleansing of the right colon (52.3% vs 38.5%; OR, 1.75; 95% CI: 1.194-2.564; P = 0.004). As compared to the high volume, 1L PEG+ASC achieved a higher cleansing success rate in out-patients (96.3%% vs 88.6%; P = 0.018) and a similar success among the in-patients (84.7% vs 76.7%; P = 0.18). No significant differences in colonoscopy performance, including caecal intubation rate (97.3% vs 96.2%, P= 0.5), withdrawal time (9.6 ± 3.2 vs 9.9 ± 4.1, P=0.3) and adenoma detection rate (25.5% vs 23.5%, P= 0.6) were found between 1L PEG+ASC and 4L PEG preparation, respectively. The 1L PEG+ASC and 4L PEG preparation did not differ significantly in terms of tolerability, as documented by the similar rate of patients reporting total adverse events (AEs) (75.1% vs 77.8%, P = 0.5), mild AEs (68.0% vs 70.3%, P = 0.6) and moderate to severe AEs (32.0% vs 29.5%, P = 0.6) after bowel preparation.

	Outpatients			Inpatients
	4L PEG (N = 123)	1L PEG-ASC (N=135)	P value	4L PEG (N = 90)	1L PEG-ASC (N = 85)	P ​value
BBPS total	7.4 ± 1.7	7.8 ± 1.4	0.035	6.6 ± 1.7	7.1 ± 1.8	0.062
BBPS partial - right colon - transverse colon - left colon	2.4 ± 0.6 2.6 ± 0.5 2.5 ± 0.6	2.6 ± 0.5 2.7 ± 0.5 2.6 ± 0.5	0.003 0.048 0.528	2.2 ± 0.6 2.4 ± 0.6 2.2 ± 0.6	2.3 ± 0.6 2.5 ± 0.6 2.5 ± 0.7	0.251 0.497 0.016
Cleansing success	109 (88.6)	130 (96.3)	0.018	69 (76.7)	72 (84.7)	0.179
Excellent cleansing	47 (38.2)	61 (45.2)	0.257	12 (13.3)	25 (29.4)	0.009
Right colon cleansing	57 (46.3)	84 (62.2)	0.010	25 (27.8)	31 (36.5)	0.218

Conclusion

Data of this randomized study showed that quality of bowel preparation for colonoscopy achieved with 1L PEG+ASC solution is not inferior as compared to that of 4L PEG. No differences in the tolerability and safety were detected. (Registration/protocol: EudraCT Number 2018-004543-24).

Disclosure

Roberto Vassallo received consultation fees from AlfaSigma and Norgine. Marcello Maida and Roberto Di Mitri served as advisory board member and received lecture grants from Norgine. Other authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript.

Introduction

Low-volume polyethylene glycol plus ascorbic acid (PEG-Asc) reduces the dosage of colonoscopic bowel preparation (BP) solution, but is still poorly tolerated. Recent studies reported that adding laxatives to the BP solution reduced the volume of fluid required, without affecting the quality. Senna, one of the anthraquinone stimulant laxatives commonly used for chronic constipation, is reported to be useful as a BP adjunctive agent. However, the appropriate dose and combination of senna and BP solutions are unclear.

Aims & Methods

This study aimed to compare 1-L PEG-Asc plus 24 mg senna (1L-PEG/AS) and conventional 2-L PEG-Asc (2L-PEG/A) regimens on BP quality and patient tolerability. A single-center, randomized, investigator-blinded, non-inferiority trial was performed between June and August 2022. Outpatients scheduled for colonoscopy were randomized (1:1) to the 1L-PEG/AS or 2L-PEG/A group. Boston Bowel Preparation Scale (BBPS) was used to evaluate the quality of BP, and adequate BP was defined as a total score ≥6 and each segmental score ≥2. The rate of adequate BP was assumed as 90% in both groups with a noninferiority margin of 10%. Compliance, adverse events and tolerability were surveyed using questionnaires. Exploratory subgroup analyses were conducted based on the potential predictor of inadequate BP (with Bonferroni correction to adjust for multiple comparisons, P<0.05/20=0.0025 was considered significant).

Results

Overall, 344 patients received either 1L-PEG/AS or 2L-PEG/A regimens. The baseline characteristics of the two groups were comparable. The 1L-PEG/AS group showed non-inferior adequate BP rates compared with the 2L-PEG/A group (88% vs. 89%, P=1.00); the overall BBPS was 7.1±1.5 and 7.2±1.5, respectively (P=0.39). More patients in the 2L-PEG/A group took <80% of solution compared to those in the 1L-PEG/AS group (17% vs. 3%, P<0.01). Nausea, vomiting, abdominal pain and discomfort, and quality of sleep, were comparable between the two groups. Higher willingness to repeat the BP was observed in the 1L-PEG/AS group (85% vs. 62%, P<0.01), and more patients in the 2L-PEG/A were unwilling to repeat BP than those in the 1L-PEG/AS group due to larger volumes of PEG-Asc consumed (49% vs. 18%, P<0.01). Exploratory subgroup analyses for adequate BP found no significant difference between the two regimens for all subgroups.

Conclusion

The 1L-PEG/AS regimen was comparable to the 2L-PEG/A regimen in terms of BP adequacy, requiring lesser BP solution volumes, with better patient tolerance. Thus, it may be a suitable alternative to the conventional BP solution for colonoscopy.

Disclosure

Nothing to disclose.

Introduction

With a growing interest in sex-specific differences in bowel preparation outcomes, current literature shows inconsistent results. Females have been associated with poor bowel preparation [1], while males may have inadequate bowel preparation due to poor compliance with instructions [2]. Analyses of randomized clinical trials of 1L polyethylene glycol (PEG) plus ascorbic acid (ASC) indicated greater high-quality (HQ) cleansing success in females than in males despite greater adenoma detection in males [3].

Aims & Methods

The effectiveness and tolerability of 1L PEG+ASC was compared in males versus females in a large real-world population. This post-hoc analysis of an observational, multi-centre, retrospective study in Spain and Portugal included patients who received 1L PEG+ASC before undergoing a colonoscopy [4]. Cleansing quality was assessed using the Boston Bowel Preparation Scale (BBPS). Adequate success was BBPS ≥6 with all segmental scores ≥2 and HQ success was BBPS ≥8 with BBPS 3 in the right colon. Polyp detection rate (PDR), adenoma detection rate (ADR) and adverse events (AEs) were also assessed. Results are reported either as mean ± SD. Chic-square test was used to compare outcomes.

Results

A total of 13,169 patients, (M/F: 6,406/6,763 aged 57.6 ± 12.7 / 56.4 ± 13.4 years) were included. The main indication for colonoscopy was (in males vs females) colorectal cancer screening: 42.5% vs 41.2%; diagnostic: 25.9% vs 32.7%; follow up: 28.6% vs 23.9%; or other: 2.9% vs 2.2%. Bowel preparations were taken either as an overnight split dose (males vs females: 32.3% vs 33.2%) or a same-day split dose (67.7% vs 66.8%). Males and females had similar (97.5% vs 97.1%) colonoscopy completion rates. Incomplete colonoscopies due to poor bowel preparation quality were rare and occurred at similar rates in males vs females (0.7% vs 0.9%).
In the overall colon, adequate success was similar in males vs females (89.5% vs 89.1%) (p = 0.40) while HQ success was more frequent in females vs males (54.1% vs 51.8%; p = 0.007). In the right colon segment, adequate success was similar in males vs females (91.4% vs 91.6%; p = 0.61), while HQ success was more frequent in females vs males (50.7% vs 47.8%; p < 0.001). The mean BBPS was similar overall and by segment (Table). As expected from the literature, the PDR and ADR were greater in males vs females in the overall colon and in the right colon (Table).

Table. Sex differences in bowel preparation parameters with 1L PEG + ASC

Variable	Males (n=6,406)	Females (n = 6,763)	P-value
Overall colon adequate success, n (%)	5,734 (89.5)	6,023 (89.1)	ns
Overall colon high-quality success, n (%)	3,317 (51.8)	3,660 (54.1)	0.007
Right colon adequate success, n (%)	5,853 (91.4)	6,196 (91.6)	ns
Right colon high-quality success, n (%)	3,063 (47.8)	3,429 (50.7)	0.0009
Overall colon total BBPS, mean ± SD Right colon BBPS, mean ± SD Transverse colon BBPS, mean ± SD Left colon BBPS, mean ± SD	7.3 ± 1.8 2.4 ± 0.7 2.5 ± 0.7 2.5 ± 0.7	7.3 ± 1.9 2.4 ± 0.7 2.5 ± 0.7 2.4 ± 0.7	ns
PDR overall colon, n (%)	3,552 (55.5)	2,926 (43.3)	<.0001
PDR right colon, n (%)	1,643 (25.7)	1,381 (20.4)	<.0001
ADR overall colon, n (%) na	2,200 (47.3) 4,654	1,753 (37.7) 4,656	<.0001
ADR right colon, n (%) na	1,139 (27.2) 4,193	915 (21.5) 4,264	<.0001

^aNumber of patients for whom histological information was available.

Males had fewer adverse events than females (1.8% vs 2.7%; p = 0.0008). While 98.2% males did not report any adverse events, those who did reported nausea (0.9%) or vomiting (0.6%). Similarly, 97.3% females did not report any adverse events, but those who did reported nausea (1.5%) or vomiting (1.0%).

Conclusion

In real-world clinical practice, 1L PEG + ASC was effective and well tolerated in both males and females. Females attained greater HQ cleansing success both overall and in the right colon.

References

References:

1. Cirocco WC et al. Dis Colon Rectum 1995; 38:964–968
2. Ness RM, et al. Am J Gastroenterol 2001; 96:1797–1802
3. Epstein M et al. Endosc Int Open 2021; 09: E1324–E1334
4. Esteban López-Jamar JM et al. UEG Journal 2022, Vol 10 (S8); OP022

Disclosure

Fatma Akriche and Carmen Turbi Disla are employees of Norgine Ltd

Introduction

Colonoscopy is used in people with chronic kidney disease receiving hemodialysis for renal replacement therapy and forms part of routine pre-transplant assessment. Concerns exist about use of oral bowel-cleansing agents for colonoscopy in people receiving haemodialysis, despite guidelines recommendations. It is plausible that intravascular depletion and consequent hypotension may cause thrombosis of the vascular access use for hemodialyisis. We evaluated the comparative efficacy, safety and tolerability a low-volume versus a high-volume polyethylene glycol based bowel preparation for colonoscopy in people on hemodialysis.

Aims & Methods

This was a multicentre, PROBE design, parallel-arm, centrally randomized, non-inferiority phase IV trial. Eligible subjects were allocated 1:1 to either low-volume (2 liters) or high-volume (4 liters) bowel preparation. The primary outcome was the proportion of participants with adequate bowel cleansing, evaluated using the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were adenoma detection rate (ADR), caecal intubation rate, patient tolerability/compliance, and adverse events (both related to colonoscopy and to dialysis/renal function). Differences were tested via t-test or Mann–Whitney U test for continuous normal variables or through chi-square or Fisher exact test for categorical ones.

Results

Sixty-nine patients were randomized in four centres, 35 to low volume and 34 to high volume groups. Mean age was 62.5±10.7 years; 54 were men and 15 were women. A total of 33 in the low-volume and 27 in high-volume completed colonoscopy; the main reasons for exclusion was stopping to take preparation (n=5). 15.No difference in caecal intubation rate was observed (100% vs 96.6%, p=1). Adequate bowel preparation was achieved in 69.7% and 63.0% of low and high-volume groups, respectively (p=0.58). Mean BBPS was similar in the two groups (5.6±2.4 vs 5.4±2.4, p=0.51). When sub-analyzing according to each bowel segment, we did not observe any difference for right, transverse nor left colon.
The ADR was 35.0% in low-volume and 37.0% in high volume (p=0.10). Median number of polyps per patient was 1.5 in low and 2 in high-volume group (p=0.45).
Mild abdominal swelling was the most common adverse event (27.3% vs 25.9% for high and low volume respectively, p=0.29), followed by mild nauseas (27.3% vs18.5%, p=0.29). A similar rate of willingness to repeat the same preparation was observed (87.9% vs 85.2%, p=0.76). No emergency dialysis sessions were required and no deaths were recorded. Levels of serum creatinine remained stable before and after preparation in both groups.

Conclusion

This small scale study based on an opportunistic sample confirms the difficulties in adequate preparation for colonoscopy in people on hemodialysis. It shows that both a low and a high-volume preparation were equally effective and safe. We did not observe a better tolerability for low-volume preparations, which may be a key findings but also due to suboptimal small sample size. Further large scale studies may be required to confirm our findings.

Introduction

Low-volume bowel preparation solutions, including 1 L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability because of the low tolerability of high-volume polyethylene glycol agents. However, 1 L PEG-A still has its typical odor that is not pleasant for most patients. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. OST may have the better tolerability because of little odor due to its tablet formula.

Aims & Methods

We aimed to investigate the efficacy, safety, and tolerability of OST compared to 1 L PEG-A. We randomized patients aged 18 years or older who underwent colonoscopy into the OST (group A) and 1 L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston bowel preparation scale (BBPS) and bubble scale. Bowel preparation success was defined as BBPS score ≥ 6. The bubble scores ranged from 0 to 3 per segment (total from 0 to 9), with a lower score indicating lower bubbles in the colonic lumen. Safety and tolerability were evaluated using a systematized questionnaire.

Results

A total of 171 patients (group A: 87, group B: 84) were included in the final analyses. The average BBPS score of group A was 8.0±1.3, which was similar to that of group B (7.7±1.4) (p=0.215). The proportion of patients showing bowel preparation success was 95.4% in the group A whereas that in the group B was 96.4% (p=0.736). The adenoma detection rate was also similar between groups A (59.6%) and B (41.9%) (p=0.087). The bubble scale in the group A was 0.2±0.9, which was significantly better that that of the group B (1.9±1.7) (p<0.001). All adverse events were mild in both groups. The group A showed lower frequency of nausea compared to the group B (14.9% vs. 38.1%, p=0.001). Overall satisfaction was better in the group A (8.1 ± 2.1 vs. 6.4 ± 2.8, p<0.001).

Conclusion

Although both OST and 1 L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy, the OST showed fewer bubbles and slightly better tolerability.