Abstract
Background and study aims
Men have more colon cleansing failures, colorectal adenomas, and colorectal cancers than women. We analyzed whether 1-liter (1 L) polyethylene glycol (PEG) NER1006 ...improves high-quality (HQ) colon cleansing and adenoma detection in males versus two mid-volume alternatives.
Patients and methods
The analysis of 1028 adult patients in two randomized clinical trials was performed. Adenoma detection and HQ cleansing were compared for overnight split dosing regimens with NER1006 (n = 513) versus combined oral sulfate solution or 2 L PEG + ascorbate (OSS/2 L PEG) (n = 515). Analyses included males versus females, overweight or obese (OO) males versus lean males, and NER1006 versus OSS/2 L PEG. In male patients, the adenoma detection rate of at least 3 (ADR3 +) was predicted with multiple logistic regression and statistical comparisons used the two-sided t-test.
Results
ADR3 + was greater in males versus females (10.7 % 56/524 versus 5.8 % 29/504; P = 0.004) despite comparable adequate cleansing success rates (93.2 % 479/514 versus 93.0 % 466/501; P = 0.912) and more HQ-scores in females (41.6 % 1069/2570 versus 45.3 % 1134/2505; P = 0.008). ADR was almost twice as high in OO versus lean males (43.4 % 184/424 versus 23.1 % 21/91; P < 0.001). Multivariate logistic regression predicted ADR3 + detection to be twice as likely in OO males using NER1006 versus OSS/2 L PEG (odds ratio (95 % confidence interval CI) = 2.049 (1.082–3.973); P = 0.030) and 90 % more likely in all males (1.902 (1.045–3.526); P = 0.037). In males, including OO males, NER1006 attained more HQ-scores per trial than OSS or 2 L PEG (P ≤ 0.017 for all comparisons).
Conclusions
NER1006 predicted the detection of more males for frequent surveillance than OSS/2 L PEG.
The 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.
Patients 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.
A 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).
NER1006 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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
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.
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< 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
< 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.
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
< 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;
P
trend = 0.003) and successfully cleansed patients (OR 1.11 1.04-1.18;
P
trend = 0.001) Figure 2. With LinR, more HQ segments per patient increased MAP in all (average increment 0.05 0.01-0.09;
P
trend = 0.012) and successfully cleansed patients (average increment 0.05 0.01-0.10;
P
trend = 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.
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