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

Abstract

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.

Conflict of interest statement

Competing Interests: Author Marc Halphen is a medical consultant for, and a previous employee of Norgine, the manufacturer of MOVIPREP (PEG+Asc), whose company funded this study. Author Hans Rudolf Kloess is an employee of Norgine. Author Wolfgang Fischbach has served as a speaker, a consultant and an advisory board member for Norgine. Author Jürgen Pohl has served as a speaker for Norgine. Medical writing assistance for the preparation of the manuscript was provided by Sarah Loftus of Insight Medical Writing Ltd, Kidlington, UK. Statistical analysis provided by: Erich Geschwentner, Pierrel Research Europe GmbH, Zeche Katharina 6, 45307 Essen, Germany. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT diagram showing patient disposition.

Fig 2. The number of patients with at least one polyp (a) or adenoma (b), overall and on the left and right sides of the colon (ITT population).

The left side includes the rectum, sigmoid colon, descending colon, left half of the transverse colon, and the right side includes the right half of the transverse colon, the ascending colon, and cecum. Adenomas were confirmed by a pathologist. Statistical significance was determined by two-sided Chi-square tests. Data are missing for one patient in the PEG+Asc treatment group. ADR, adenoma detection rate; NaPic/MgCit, sodium picosulfate/magnesium citrate; PDR, polyp detection rate; PEG+Asc, polyethylene glycol plus ascorbate.

Fig 3. The numbers of patients with at least one carcinoma, flat lesion or advanced risk lesion (ITT population).

Statistical significance was determined by two-sided Chi-square tests. Data are missing for one patient in the PEG+Asc treatment group. NaPic/MgCit, sodium picosulfate/magnesium citrate; PEG+Asc, polyethylene glycol plus ascorbate.

Fig 4. Assessments of cleansing using the Harefield Cleansing Scale [20] (ITT population).

(a) The percentage of patients with Grade 4 (Very good) or Grade 3 (Good) cleansing quality in various areas of the colon. Results are presented for those patients who received PEG+Asc and NaPic/MgCit bowel preparations. NaPic/MgCit, sodium picosulfate/magnesium citrate; PEG+Asc, polyethylene glycol plus ascorbate. (b) Overall colon cleansing success of PEG+Asc compared to NaPic/MgCit assessed during withdrawal of the colonoscope.

Fig 5. Tolerance of PEG+Asc and NaPic/MgCit assessed by patients via a questionnaire (Safety population).

The percentages of patients who reported “Very good”, “Good” or “Acceptable” (Very Good—Acceptable) tolerance are presented for each treatment group together with the percentages of patients who reported that they had no problems while drinking the bowel cleansing solution. NaPic/MgCit, sodium picosulfate/magnesium citrate; PEG+Asc, polyethylene glycol plus ascorbate.