ESGE: European Society of Gastrointestinal Endoscopy

BBPS: Boston Bowel Preparation Scale

IQR: interquartile range

CRC: colorectal cancer

PEG: polyethylene glycol

Colonoscopy is the gold standard for colorectal cancer (CRC) screening and prevention, enabling both early detection and removal of precancerous lesions, thereby directly reducing disease incidence. Despite these advances, CRC remains the third most common malignancy in the United States and the second leading cause of cancer-related death. Early-stage diagnosis (stage T1) carries a five-year survival rate above 90%, yet fewer than 40% of cases are detected at this stage.^[1]

A prerequisite for successful colonoscopy is effective bowel preparation. Inadequate cleansing undermines almost all aspects of the procedure: it reduces the detection rate of adenomas, complicates cecal intubation, reduces the extraction rate of polyps, prolongs the procedure time, and negatively impacts the patient experience. These shortcomings often result in shorter surveillance intervals, higher rates of repeat examinations, longer hospital stays, and increased healthcare costs.^[2]

Given the significant clinical and economic implications, we conducted a multi-center study to compare the efficacy of various bowel preparation methods using high-volume polyethylene glycol (PEG)-based solution (Endofalk). The primary endpoints evaluated in this research are the quality of the bowel cleaning, cost-effectiveness, and patient tolerability. The quality of bowel cleaning was assessed by identifying which regimen resulted in the best mucosal preparation. Cost-effectiveness was determined based on the extent to which each regimen reduced healthcare facility expenses. Last but not least, patient tolerability was evaluated by examining which regimen they found most comfortable and easiest to adhere to.

Between January 2024 and May 2024, we enrolled 773 patients aged 18-88 years at three centers—Pulmed University Hospital in Plovdiv, Sofiamed University Hospital in Sofia, and the Military Medical Academy in Sofia (Table 1).

Written consent was obtained from all patients before the procedure. All patients were admitted to the hospital one day prior to the scheduled colonoscopy to confirm there was no medical risk for the procedure. Inclusion criteria were colorectal cancer screening, change in bowel habits, unintentional weight loss, anemia, refractory abdominal pain, suspected or surveillance of inflammatory bowel disease, personal or family history of adenomatous polyps, and evaluation of radiologic findings. Exclusion criteria were contraindications for bowel preparation (mechanical gastrointestinal obstruction or ileus, bowel perforation or suspected perforation, toxic megacolon, fulminant colitis), hypersensitivity to polyethylene glycol, swallowing disorders, severe heart failure, severe respiratory failure, severe renal insufficiency, electrolyte imbalances, pregnancy, and the patient’s refusal or inability to cooperate.

The laxative of choice was Endofalk, a high-volume polyethylene glycol-based product. Different preparation methods were grouped into three distinct regimens: previous-day regimen, split-dose regimen, and same-day regimen. Participants were randomly assigned to different bowel preparation protocols. Every patient received standardized oral and written instructions on how to take the PEG-based solution. To maximize patient compliance, we sought the regimen that delivered optimal bowel cleansing with the fewest sachets and the lowest total water volume. Initially, a total of nine combinations of preparation methods were evaluated. The three underperforming regimens (PD3*, SPLIT5*, and SD1*) were discontinued prematurely, which led to excluding 27 patients for inadequate cleansing, and the study proceeded with 746 patients in the final analysis.

Consistent with the European Society of Gastrointestinal Endoscopy (ESGE) guidelines, all patients followed a low-fiber diet at least two days before the colonoscopy and a clear liquid diet on the day of the preparation. In addition, all colonoscopies were performed at least 2 hours after the last administration of Endofalk.^[2]

Our multi-center study demonstrates that bowel preparation with high-volume PEG-based Endofalk is most effective when administered in a split-dose regimen. Patients who received split dosing, particularly the SPLIT4 schedule, achieved the highest BBPS scores. This indicates superior mucosal cleanliness, likely because the split regimen ensured a “booster” dose closer to the colonoscopy, flushing residual colonic content. In contrast, purely previous-day regimens showed comparatively lower cleansing efficacy, underscoring the importance of timing. Notably, the SPLIT4 regimen not only maximized cleansing but also maintained high patient tolerability, an encouraging combination for clinical practice. The European Society of Gastrointestinal Endoscopy strongly recommends split-dose bowel preparation for elective colonoscopy, based on high-quality evidence that splitting improves cleansing quality.^[2] A comprehensive meta-analysis of 47 trials similarly found that split-dose regimens yielded significantly better colon cleanliness than day-before regimens.^[4]

Furthermore, our results provide insight into patient tolerability of different regimens, which is an important practical consideration. Interestingly, despite the high volume of PEG, patients rated tolerability highest with PD1, PD2, and SPLIT4 schedules. Previous studies have noted that the split-dose prep, while medically advantageous, can be a “social” inconvenience and feel burdensome for some. In contrast, the prior-day regimens let the patients complete the preparation well before bedtime and avoid sleep disruption.^[5] The SPLIT4 regimen appears to mitigate this issue by using a smaller morning dose, 1 L, which may explain why its tolerability was similar to the day-before methods. In this way, SPLIT4 preserved the efficacy of split-dosing while minimizing complaints.

A key limitation of our study is its unblinded design. Both patients and endoscopists necessarily knew the timing of the bowel prep, which could have influenced BBPS scoring despite objective criteria. Additionally, unmeasured patient-level factors—such as socioeconomic status, health literacy, and comorbidity—could have affected adherence to the regimen and, in turn, cleansing quality. Moreover, we evaluated only a high-volume PEG solution, so our findings cannot be applied to low-volume PEG regimens. In fact, a recent systematic review and meta-analysis reported that while high- and low-volume PEG mixtures achieve comparable bowel cleanliness, low-volume formulations are linked to greater willingness to repeat the prep and fewer adverse reactions.^[6] Future research should therefore assess whether split-dose scheduling delivers the same benefits when using lower-volume preparations.

Despite these limitations, our findings are consistent with previously established evidence.^{[2, 3]} The large, diverse multicenter cohort strengthens our conclusions and offers practical guidance for improving bowel preparation in routine endoscopy.

In conclusion, this multi-center study confirms that split-dose regimens of high-volume PEG (Endofalk) provide superior colon cleansing compared to traditional day-before preparations. Patients who underwent a split-dose schedule—in particular the SPLIT4 regimen, which uses a larger evening dose and a small morning top-up—achieved the highest BBPS cleanliness scores while still reporting excellent tolerability. By contrast, solely prior-day regimens were somewhat less effective in cleansing, although they were convenient for patients. Endoscopists should favor split-dose scheduling whenever possible, as recommended by current guidelines, to maximize mucosal visibility and adenoma detection rates. However, one size does not fit all—individual priorities vary; some patients may value convenience over optimal cleansing, underscoring the need to tailor bowel preparation regimens to each patient’s preferences.

Conceptualization: N.B. and N.M.; methodology: A.B.; software: S.T.; validation: A.K., I.P., and G.H.; formal analysis: I.T. and K.M.; investigation: N.B.; resources: N.B. and K.S.; data curation: S.T.; writing—original draft preparation: N.M.; writing—review and editing: A.B.; visualization: N.B.; supervision: A.K., I.P., and G.H.; project administration: N.M. All authors have read and agreed to the published version of the manuscript.

We confirm that neither the manuscript nor any parts of its content are currently under consideration or published in another journal. The manuscript has been approved by all authors, and they agreed to submit it to the Folia Medica journal.

This study was approved by the Medical Ethics Committee at UMHAT Pulmed OOD.

The authors have no funding to report.