Adequate bowel preparation is essential for effective colonoscopies [1-5]. Poor bowel preparation results in missed polyps, increased risk of procedural adverse events, and the necessity for repeated examinations [2,5]. An ideal bowel cleansing agent should rapidly empty the fecal material without causing mucosal alteration of the colon or causing electrolyte imbalance. In addition, it should be tolerable and easy to consume [1,2,4]. No available agent satisfies all these characteristics.

High-volume (4-L) polyethylene glycol (PEG) has been widely used for bowel preparation because of its cleaning efficacy and safety [6]. However, some patients do not fully consume the preparation because of the large volume and poor palatability [1]. Low-volume bowel preparations seek to improve patient tolerability. Two-liter PEG with additional ascorbic acid as a laxative (AA + PEG) has similar efficacy compared to 4-L PEG [7,8]. AA + PEG is safe for most patients except for those who are deficient in glucose-6-phosphate dehydrogenase [8,9].

In 2009, a new osmotic preparation termed oral sulfate solution (OSS) was developed for bowel cleansing [10]. This hyperosmolar preparation does not cause significant fluid or electrolyte shifts possibly because sulfate is a poorly absorbed anion. The preparation regimen involves consumption of a reduced volume (946 mL) of the preparation solution and 1,892 mL of water with additional fluid consumption permissible [1,11].

Recent studies have demonstrated the efficacy of OSS compared to conventional bowel cleansing agents and shown comparable or better efficacy with an acceptable safety profile [10-15]. Three of these studies have compared the efficacy of OSS with AA + PEG using a non-inferiority design. However, their study subjects were Americans [11,12,14]. Such data for Asians are lacking.

Thus, the objective of this randomized, prospective, investigator-blind, parallel study was to compare the efficacy and tolerability of OSS to AA + PEG in Asian patients. Both preparations were in low-volume and given as split doses according to the Korea and United States Food and Drug Administration approved regimens. Outcomes included effectiveness in bowel cleansing, tolerability, and compliance with the preparation.

We described a prospective, randomized, parallel, investigator-blind trial that compared the efficacy, safety, and tolerability between OSS and AA + PEG bowel preparations. This is the first report to analyze the efficacy and acceptability of OSS formulation in Korean subjects. Clinical outcomes were collected from 173 patients at university hospitals in Korea during screening colonoscopies. We demonstrated that OSS was superior to AA + PEG for colon cleansing. Tolerability and adverse events associated with these two preparations were similar except for nausea and abdominal cramping. However, these adverse events were generally acceptable.

A previous study has shown that OSS provides superior segmental cleansing compared to 4 L PEG [13]. However, OSS was not directly compared to 4 L split-dose PEG [13]. Cleansing efficacies were worse if subjects received full AA + PEG dose in the evening before the procedure compared to split-dose [7]. In this study, splitdose regimens of OSS and AA + PEG were implemented to provide more successful preparation efficacy and less gastrointestinal adverse events compared to the sameday regimen [11].

Previous studies have frequently used OBPS and BBPS bowel cleansing scoring systems [16,17]. The BBPS is a valid and reliable measure of bowel preparation that aggregates scores of three broad segments of the colon rated during withdrawal of the colonoscope after washing and suctioning of the fluid. Consequently, this scoring system does not include the quantity of fluid in the colon which requires various other scores [16]. The OBPS rates three colonic segments independently. Their scores are then summed at the end of the colonoscopic examination to give a total score. Furthermore, the OBPS includes an overall fluid quantity in the colon (rated 0 to 2) which allows subjective estimation of residual liquid. Thus, OBPS is a simple, objectively framed bowel preparation quality scale that assesses colonic segments individually and overall colonic fluid. It provides a summary score for the entire colon. This scale has high inter-observer reliability for total scoring and segmental colonic preparation quality [17]. The strength of our study was that we used two overall grading scales which included segmental scoring to validate the quality of the bowel preparation. Segmental scoring was conducted separately. Results supported the overall efficacy. Scores for the three colon sections were significantly higher in the OSS group than those in the AA + PEG group.

Adenoma detection rate is defined as the percentage of procedures per colonoscopist in which at least one adenoma is detected. It has been considered as a strong quality indicator for effective colonoscopy [19-22]. However, most patients enrolled in the present study had experience of colonoscopic examination or a prior history of colon polyp. We could not analyze polyp detection rate or adenoma detection rate for this reason. There was no difference between the two study groups regarding serious adverse events except for nausea and abdominal cramping which did not require further medical management. In the symptom questionnaire, the OSS group scored significantly higher for nausea and abdominal cramping compared to the AA + PEG group. Differences in taste among Asian subjects may cause higher scores for nausea than other Caucasian studies [11,13,14]. However, the degree of adverse symptoms in both groups was less than mild. There were no significant differences between the two groups for taste, stomach bloating, or sleep disturbance. These problems were also acceptable.

Our study has several limitations. First, we used a cleansing score that assessed three bowel segments. Recent studies have shown a more detailed evaluation that divides the colon into five or six segments [7,23]. However, both BBPS and OBPS scores have been extensively validated for general use in clinical studies [16]. Second, inter-investigator variation for bowel preparation scores unfortunately occurred in this investigation. Colonoscopists in two hospitals had no opportunity to reach a sufficient agreement about measurement of two bowel preparation scales. Third, AA + PEG bowel preparation adequacy scored less than that reported by other studies (88% to 90%) [7,24]. The small number of subjects enrolled in our study might have led to this discrepancy.

In summary, OSS provided a non-inferior efficacious bowel cleansing than AA + PEG regimen without compromising safety or tolerability. Bowel cleansing quality and patients’ acceptance of the OSS formulation in Asian people indicate the potential of OSS as an alternative bowel cleansing method to AA + PEG for clinical use. Further prospective studies in larger populations are needed to confirm this finding.