Journal List > J Korean Med Sci > v.39(48) > 1516089027

TOOLS
Jung, Kim, Yang, Kang, Park, Baek, Chun, Gweon, Goong, Kwak, Lee, Park, and Lee: Efficacy of Oral Sulfate Tablet and 2 L-Polyethylene Glycol With Ascorbic Acid for Bowel Preparation: A Prospective Randomized KASID Multicenter Trial
Original Article
Gastroenterology & Hepatology

Journal of Korean Medical Science 2024; 39(48): e301.

Published online: 7 October 2024

DOI: https://doi.org/10.3346/jkms.2024.39.e301

Efficacy of Oral Sulfate Tablet and 2 L-Polyethylene Glycol With Ascorbic Acid for Bowel Preparation: A Prospective Randomized KASID Multicenter Trial

Yunho Jung1, Hyun Gun Kim2, Dong-Hoon Yang3, Hyoun Woo Kang4, Jae Jun Park5, Dong Hoon Baek6, Jaeyoung Chun7, Tae-Geun Gweon8, Hyeon Jeong Goong9, Min Seob Kwak10, Hyun Jung Lee11, Soo-Kyung Park12, Jong Hoon Lee13

1Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.

2Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea.

3Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

4Department of Gastroenterology, Seoul National University Boramae Medical Center, Seoul, Korea.

5Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

6Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.

7Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

8Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

9Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea.

10Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.

11Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

12Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

13Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.

Address for Correspondence: Hyun Gun Kim, MD, PhD. Division of Gastroenterology, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea. medgun@schmc.ac.kr

Received 4 June 2024       Accepted 2 September 2024

© 2024 The Korean Academy of Medical Sciences.

The Korean Academy of Medical Sciences

https://creativecommons.org/licenses/by-nc/4.0/
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Oral sulfate tablets (OSTs) are bowel preparation agents that combine oral sulfate solution and simethicone. This study compared the efficacy, tolerability, and safety of OST compared to 2 L-polyethylene glycol plus ascorbic acid (2 L-PEG/ASC).

Methods

This prospective, randomized, controlled, single-blinded, multicenter, noninferiority trial enrolled 211 healthy adults who underwent colonoscopy between May 2020 and September 2022 at 13 university hospitals. The bowel cleansing rate was assessed using the Boston Bowel Preparation Scale (BBPS) and Harefield Cleansing Scale (HCS), and the preparation agents were administered in split regimens.

Results

The total BBPS score (8.2 ± 1.5 vs. 7.8 ± 1.4, p = 0.040) and the high-quality bowel cleansing rates in the right colon (73.2% vs. 50.5), transverse colon (80.6% vs. 68.0%), and left colon (81.5% vs. 67.0%) on the BBPS were significantly higher in the OST group than in the 2 L-PEG/ASC group. However, the rates of successful cleansing according to BBPS (90.7% vs. 91.2%) and HCS (96.3% vs. 94.2%) did not significantly differ between the two groups. The taste, ease, and amount of consumption of the preparation agent; and willingness to repeat colonoscopy with the same agent (89.8% vs. 78.6%, P = 0.026) were significantly better in the OST group compared to the 2 L-PEG/ASC group. Adverse events and clinically significant laboratory changes were not significantly different between the two groups.

Conclusion

The OST was not inferior to 2 L-PEG/ASC in terms of bowel cleansing efficacy and showed better tolerability when used for bowel preparation for colonoscopy.

Trial Registration

Clinical Research Information Service Identifier: KCT0005017

Graphical Abstract

jkms-39-e301-abf001.jpg

Keywords: Colonoscopy, Bowel Preparation, Polyethylene Glycol, Sulfate

INTRODUCTION

Adequate bowel preparation is essential for high-quality colonoscopy, both for the endoscopic diagnosis and treatment of colorectal neoplasms, as well as for post-polypectomy surveillance.1234 Therefore, selection of an effective agent is important. Novel agents have been developed with the aim of improving both bowel cleansing and patient compliance. Use of polyethylene glycol (PEG)-based solutions began in the 1980s.5 These are widely used worldwide, because they are non-absorbable iso-osmotic solutions with excellent bowel cleaning effects and no significant fluid or electrolyte shifts. The 4 L-PEG solution is one such agent. However, despite its excellent efficacy and safety, it is not currently widely used because of the large volume ingested and its unpleasant taste. Indeed, it has been estimated that 15% to 20% of patients have difficulty taking the agent.67 To improve patient tolerability, agents with smaller required volumes (such as 2 L-8 and 1 L-PEG solution9) and improved taste (such as sulfate-free PEG solution) have been developed.6 However, patient compliance with bowel preparation regimes is still an issue, and about one-third of patients do not wish to again undergo colonoscopy using the same agents.10
Oral sulfate solution (OSS), also called trisulfate, consists of magnesium sulfate, sodium sulfate, and potassium sulfate. Adequate bowel preparation has reportedly been achieved by 98.0% of patients who use it, noninferior to the 96% for 4 L-PEG. Although the rates of acceptance, compliance, and satisfaction are significantly higher for OSS than for 4 L-PEG, gastrointestinal (GI) adverse symptoms may not be significantly improved. Furthermore, abdominal pain may be more frequent with OSS than with 4 L-PEG.11 In a meta-analysis of OSS and 2 L-PEG with ascorbic acid (2 L-PEG/ASC), the rates of successful bowel cleansing and adverse GI events (such as nausea, abdominal distension, and abdominal discomfort) were not significantly different between the two preparation agents. However, the excellent bowel preparation rate was significantly higher with OSS than with 2 L-PEG/ASC, whereas the mean intensity of vomiting was higher with OSS.12
Oral sulfate tablets (OSTs) (Orafang; Pharmbio Korea Co., Seoul, Korea) were recently developed to enhance GI comfort and tolerability. Orafang is composed of 28 tablets, each containing a blend of three sulfates—sodium sulfate, potassium sulfate, and magnesium sulfate—acting as osmotic laxatives, similar to OSS. Additionally, simethicone is included as a defoaming agent to reduce bubble formation. A phase 3 study showed that the bowel cleansing rate of OST was noninferior to that of OSS and its tolerability was superior.13 However, comparisons of OST with other bowel preparation agents are lacking. Thus, we compared the efficacy, tolerability, and safety of OST and 2 L-PEG/ASC.

METHODS

Study design

This was a prospective, randomized, controlled, colonoscopist-blinded, multicenter, noninferiority trial that enrolled 211 healthy adults who underwent colonoscopy between May 2020 and September 2022 at 13 university hospitals.

Study population

Eligible patients were consecutive men and women aged 19 to 75 years with a body mass index (BMI) ≥ 19 to < 30 kg/m2 who underwent scheduled colonoscopy. The exclusion criteria were as follows: acute myocardial infarction within 1 year; advanced congestive heart failure (NYHA III or IV); inflammatory bowel disease; previous significant GI surgery; known or suspected ileus, gastric retention, bowel perforation, or obstruction in the previous 12 months; history of significant constipation (< 3 bowel movements per week regardless of regular laxatives); regular use of laxatives or colon motility-altering drugs; and severe renal insufficiency (serum creatinine > 3 mg/dL).

Bowel preparation protocol

Following written consent, patients were randomly allocated in a 1:1 ratio to either the OST group (Orafang tablets, Pharmbio Korea; composition per tablet: anhydrous sodium sulfate 1,125 mg, potassium sulfate 201.07 mg, anhydrous magnesium sulfate 102.86 mg, simethicone 11.43 mg) or the 2 L-PEG/ASC group (Haprep powder, Pharmbio Korea; composition per liter: sodium chloride 2.89 g, potassium chloride 1.015 g, anhydrous sodium sulfate 7.5 g, PEG 3350 100 g, ascorbic acid 4.7 g, sodium ascorbate 5.9 g). Assignment was based on computer-generated random numbers issued to consecutive patients at the time of scheduling their colonoscopies, which were all conducted between 9 a.m. and 1 p.m.
On the day of randomization, participants were given detailed instructions on bowel preparation methods and dietary restrictions through a leaflet provided by the primary study hospital. They were instructed to follow a low-residue diet starting 3 days before their colonoscopy and to transition to a clear liquid diet beginning the afternoon before the procedure. Compliance with these dietary guidelines was assessed using a Yes/No survey. Both groups followed a split-dose regimen for bowel preparation. Patients in the OST group took a total of 14 tablets of Orafang with 425 mL water and drank the same amount of free water for the next hours in the evening (6–8 p.m.) of the day before the colonoscopy. Patients in the 2 L-PEG/ASC group drank 1 L Haprep solution with a further 500 mL free water in the evening of the day before the colonoscopy. The same procedures were repeated with the same agents early in the morning of the next day for colonoscopy in both groups. All preparations were completed at least two hours before the examination, ensuring that the colonoscopies were performed within 5 hours of the last dose of agent.

Assessments and endpoints

The principal investigator, colonoscopists, and endoscopy assistant nurses were blinded to the agent assignments until the completion of the study. High-definition colonoscopes (260 and 290 series; Olympus America, Center Valley, PA, USA) were used to measure the efficacy of bowel cleansing in all colon segments.
The primary outcome was the efficacy of bowel cleansing using the 5-point (0–4) Harefield Cleansing Scale (HCS), which assigns scores to five segments (cecum [CE], ascending colon [AC], transverse colon [TC], descending colon [DC], sigmoid colon [SC], and rectum [RC]).14 Overall HCS grade was categorized as: A (all segments scored 3 or 4), B (≥ 1 segment scored 2 but no segment scored < 2), C (≥ 1 segment scored 1 but no segment scored < 1), and D (≥ 1 segment scored 0). We also used the 4-point (0–3) Boston Bowel Preparation Scale (BBPS), which assigns scores to three segments (right colon [CE and AC], TC, and left colon [DC, SC, and RC]).15 The HCS and BBPS scores were measured simultaneously during colonoscopies. Successful overall bowel preparation was defined as an overall HCS grade of A or B and ≥ 2 scores for all segments on the BBPS. High-quality overall preparation was defined as an overall HCS grade of A. High-quality preparation as determined in segmental evaluations was defined as grade A (score 3 or 4) on the HCS and a score of 3 on the BBPS. To reduce interobserver variation in the assessment of preparation quality using the BBPS and HCS, we provided educational materials for use during each procedure (Supplementary Fig. 1). Additionally, before starting the study, we held in-person meetings to discuss and coordinate the training and standardization efforts.
The secondary endpoints were the polyp detection rate (PDR) and adenoma detection rate (ADR) calculated as the percentage of patients with at least one polyp (PDR) or adenoma (ADR) in the analyzed population. The mean number of adenoma detections per colonoscopy and the cancer detection rate were also evaluated.

Evaluation of tolerability and safety

Tolerability and safety were evaluated using a questionnaire. Tolerability was evaluated in terms of ‘degree of difficulty with bowel preparation protocol,’ ‘taste of the preparation agent,’ ‘ease and amount of consumption of the preparation agent,’ and ‘willingness to repeat colonoscopy with the same agent.’ The first was evaluated using a 3-point scale (1 = easy, 2 = tolerable, and 3 = difficult), the second two were evaluated using a 10-point scale of 1 (worst) to 10 (best), and the final item was evaluated using Yes/No questions inquiring about patient satisfaction. Safety was assessed through adverse events reporting, clinical and laboratory evaluations, vital signs, and physical examinations. Adverse events related to bowel preparation were nausea, vomiting, abdominal pain, thirst, dehydration, headache, dizziness, lethargy, and others. The participants underwent blood tests for levels of blood urea nitrogen, creatinine, and electrolytes such as sodium, potassium, chloride, calcium, phosphate, and magnesium on the day of the colonoscopy, prior to the procedure.

Statistical analysis

The primary outcome was inferiority/noninferiority of OST compared to 2 L-PEG/ASC in terms of bowel cleansing efficacy. The upper limit of noninferiority was set at 10%, the standard acceptable level for noninferiority in previous bowel preparation studies.161718192021 Assuming an overall bowel cleansing success rate of 94.8% for the 2 L-PEG/ASC group,22 and with a noninferiority margin of 10% and a one-sided significance threshold of P < 0.025, a sample of 104 patients per group provided a statistical power of at least 90% to demonstrate noninferiority. Ultimately, 232 patients per group were analyzed after applying a dropout rate of 10%. For secondary outcomes, continuous variables are presented as means ± SDs and were analyzed using Student’s t-test or Wilcoxon rank-sum test. Categorical variables are described as frequencies and proportions and were analyzed using the χ2 test or Fisher’s exact test. Two-sided values of P < 0.05 were considered indicative of statistical significance. Summary and descriptive statistics were calculated where appropriate. Statistical analysis was conducted using SAS software (v. 9.4; SAS Institute, Cary, NC, USA).

Ethics statement

This study was approved by the Ethics Committees of the participating institutions and is registered at the Clinical Research Information Service (KCT0005017; https://cris.nih.go.kr/cris/en/index.jsp). Informed consent was obtained from all patients before their enrollment. The study was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Boards of Soonchunhyang University Hospital Seoul [Soonchunhyang Universtiy Hospital (SCHUH) 2020–03–015].

RESULTS

In all, 232 patients were randomized to the OST group (n = 116) and 2 L-PEG/ASC group (n = 116). Of them, 21 patients were excluded, among which 14 patients withdrew consent and 2 did not take the bowel preparation agents due to personal circumstances related to work. In addition, five patients did not comply with the study protocol, such as not submitting a questionnaire and not having a blood test performed. All were excluded from the per-protocol (PP) analysis. The PP population (n = 211) consisted of 108 patients in the OST group and 103 patients in 2 L-PEG/ASC group (Fig. 1).
Fig. 1

Study flowchart (OST, oral sulfate tablet; PEG, polyethylene glycol).

OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid.
jkms-39-e301-g001
Baseline characteristics were balanced between the groups (Table 1). The mean age, sex, BMI, and indication for colonoscopy were not significantly different between the groups. The interval from the last dose of bowel purgative intake to colonoscopy and comorbidities such as hypertension and diabetes mellitus were also not significantly different between the groups. Complete colonoscopy with cecal intubation was achieved in all patients.
Table 1

Baseline characteristics of the patients

jkms-39-e301-i001
Variables OST group (n = 108) 2 L-PEG/ASC group (n = 103) P value
Age, yr 54.5 ± 12.1 52.0 ± 13.0 0.162
Sex 0.015
Male 49 (45.4) 64 (62.1)
Female 59 (54.6) 39 (37.9)
HTN 35 (32.4) 24 (23.3) 0.141
DM 9 (8.3) 10 (9.7) 0.727
BMI 24.3 ± 3.0 24.2 ± 2.8 0.900
Indication for colonoscopy
Screening 58 (53.7) 58 (56.3)
Surveillance 50 (46.3) 45 (43.7)
No. of bowel movements after preparation 0.254
≤ 5 1 (0.9) 3 (2.9)
6–9 32 (29.6) 30 (29.1)
10–12 41 (38.8) 48 (46.6)
≥ 13 34 (31.5) 22 (21.4)
Time interval from the last dose of bowel purgative intake to colonoscopy, hr 0.186
3–5 96 (88.9) 85 (82.5)
5–7 12 (11.1) 18 (17.5)
Diet control 106 (98.2) 98 (95.2) 0.145
Values are presented as number (%) or mean ± standard deviation.
OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid, HTN = hypertension, DM = diabetes mellitus, BMI = body mass index.

Efficacy of bowel cleansing

OST was noninferior to 2 L-PEG/ASC for the primary efficacy endpoint. The overall successful bowel cleansing rates based on the HCS grade (A or B) (OST: 96.3% [104/108] vs. 2 L-PEG/ASC: 94.2% [97/103], Δ = 2.1%; one-sided lower 97.5% confidence limit, -3.6%; test for superiority, P = 0.531) and BBPS score (each segment ≥ 2) (OST 90.7% [98/108] vs. 2 L-PEG/ASC 91.2% [94/103], Δ = -0.5%; one-sided lower 97.5% confidence limit, -8.2%; test for superiority, P = 0.895) were noninferior in the OST group compared to the 2 L-PEG/ASC group.
The mean overall BBPS scores (8.2 ± 1.5 vs. 7.8 ± 1.4, P = 0.040) and high-quality bowel cleansing rates based on the BBPS score (score 3) in the right colon (73.2% vs. 50.5%, P = 0.002), transverse colon (80.6% vs. 68.0%, P = 0.016), and left colon (81.5% vs. 67.0%, P = 0.004) were significantly higher in the OST group than in the 2 L-PEG/ASC group (Fig. 2A). However, the high-quality rate based on the HCS (grade A) was not significantly different between the two groups overall (77.8% vs. 70.9%, P = 0.251) or in the right colon, descending colon, sigmoid colon, or rectum, but there was a significant difference in the transverse colon (93.5% vs. 84.5%, P = 0.035) (Fig. 2B). There were significantly fewer intraluminal bubbles in the OST group than the 2 L-PEG/ASC group (P < 0.001) (Table 2).
Fig. 2

Efficacy of bowel cleansing as evaluated by (A) BBPS and (B) HCS.

BBPS = Boston Bowel Preparation Scale, HCS = Hareeld Cleansing Scale, LCL = lower condence limit, OSS = oral sulfate solution, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid, Δ = difference in rates of successful bowel cleansing.
jkms-39-e301-g002
Table 2

Bowel preparation efficacy

jkms-39-e301-i002
Variables OST group (n = 108) 2 L-PEG/ASC group (n = 103) P value
Boston Bowel Preparation Scale
Total score 8.2 ± 1.5 7.8 ± 1.4 0.040
Successful cleansing (each segment ≥ 2) 98 (90.7) 94 (91.3) 0.895
High-quality cleansing (score 3 of each segment)
Right-sided colon 79 (73.2) 52 (50.5) 0.002
Transverse colon 87 (80.6) 70 (68.0) 0.016
Left-sided colon 88 (81.5) 69 (67.0) 0.004
Harefield Cleansing Scale
Colon cleansing grade
Grade A 84 (77.8) 73 (70.9) 0.251
Grade B 20 (18.5) 24 (23.3) 0.393
Grade C o D 4 (3.7) 6 (5.8) 0.531
Successful cleansing (grade A/B) 104 (96.3) 97 (94.2) 0.531
High-quality cleansing (grade A)
Right-sided colon 88 (81.5) 77 (74.8) 0.237
Transverse colon 101 (93.5) 87 (84.5) 0.035
Descending colon 91 (84.3) 92 (89.3) 0.279
Sigmoid colon 96 (88.9) 91 (88.4) 0.909
Rectum 99 (91.7) 96 (93.2) 0.673
Bubble score < 0.001
1 (no or minimal) 105 (97.2) 62 (60.2)
2 (moderate, limited to detecting 5 mm. polyps) 3 (2.8) 29 (28.2)
3 (severe, limited to detecting 10 mm. polyps) 0 12 (11.6)
Values are presented as number (%) or mean ± standard deviation.
OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid.
The endoscopic outcomes such as PDR (51% vs. 49.5%, P = 0838), ADR (30.6% vs. 36.9%, P = 0.330), mean adenoma detection per colonoscopy (0.6 ± 1.3 vs. 0.8 ± 1.7, P = 0.341), and cancer detection were not significantly differ between the groups (Table 3).
Table 3

Outcomes of colonoscopy

jkms-39-e301-i003
Variables OST group (n = 108) 2 L-PEG/ASC group (n = 103) P value
Cecal intubation rate 108 (100) 103 (100) 1.000
Polyp detection rate 55 (51.0) 51 (49.5) 0.838
Adenoma detection rate 33 (30.6) 38 (36.9) 0.330
Mean number of adenoma detection per colonoscopy 0.6 ± 1.3 0.8 ± 1.7 0.341
Cancer detection rate 1 (0.9) 0 1.000
Colonoscopy withdrawal time, min 9.7 ± 5.9 10.4 ± 6.6 0.380
Values are presented as number (%) or mean ± standard deviation.
OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid.

Tolerability

The rate of protocol completion (100% of OST vs. 98.1% of 2 L-PEG/ASC, P = 0.237) and the degree of difficulty with preparation protocol were not significantly different between the two groups. Taste (7.9 ± 2.7 vs. 6.5 ± 2.3, P < 0.001), ease of consumption (7.8 ± 2.5 vs. 6.5 ± 2.3, P < 0.001), and amount of consumption (6.9 ± 2.6 vs. 6.1 ± 2.5, P = 0.024) were significantly better in the OST group. The rate of willingness to repeat colonoscopy with the same agent (89.8% vs. 78.6%, P = 0.026) was significantly higher in the OST group (Fig. 3 and Table 4).
Fig. 3

Percentage of participants who responded “yes” to the question “Willingness to repeat colonoscopy with the same agent.”

OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid.
jkms-39-e301-g003
Table 4

Bowel preparation tolerability

jkms-39-e301-i004
Variables OST group (n = 108) 2 L-PEG/ASC group (n = 103) P value
Completeness of bowel preparation protocol 108 (100) 101 (98.1) 0.237
Degree of difficulty in bowel preparation protocol 0.213
Easy 71 (65.7) 56 (54.4)
Tolerable 33 (30.6) 43 (41.8)
Difficult 4 (3.7) 4 (3.88)
Taste of the preparation agent (0–10)a 7.9 ± 2.7 6.5 ± 2.3 < 0.001
Ease of consumption of the preparation agent (0–10)a 7.8 ± 2.5 6.5 ± 2.3 < 0.001
Amount of consumption of the preparation agent (0–10)a 6.9 ± 2.6 6.1 ± 2.5 0.024
Willingness to repeat colonoscopy with the same agent 97 (89.8) 81 (78.6) 0.026
Values are presented as number (%) or mean ± standard deviation.
OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid.
a0 (bad), 10 (good).

Safety

There were no serious adverse events in either group. Any adverse events and any GI adverse events including nausea (28.7% vs. 20.4%, P = 0.161) vomiting (5.6% vs. 1.0%, P = 0.120), abdominal pain (12.0% vs. 15.5%, P = 0.461), and bloating (34.3% vs. 32.0%, P = 0.732) were not significantly different between the groups. The proportions of patients with clinically abnormal electrolytes (8.3% vs. 4.9%, P = 3.100) as well as the estimated glomerular filtration rate (1.9% vs. 2.9%, P = 0.677) were not significantly different between the two groups (Tables 5 and 6).
Table 5

Safety of bowel preparation

jkms-39-e301-i005
Variables OST group (n = 108) 2 L-PEG/ASC group (n = 103) P value
Serious adverse events or death 0 0 NA
Any of adverse events 67 (62.0) 55 (53.4) 0.204
Any of GI adverse events 60 (55.6) 47 (45.6) 0.150
Mild adverse events
Nausea 31 (28.7) 21 (20.4) 0.161
Vomiting 6 (5.6) 1 (1.0) 0.120
Abdominal pain 13 (12.0) 16 (15.5) 0.461
Bloating 37 (34.3) 33 (32.0) 0.732
Thirst, dry mouth 14 (13.0) 16 (15.5) 0.593
Headache 3 (2.8) 5 (4.9) 0.491
Dizziness 15 (13.9) 10 (9.7) 0.348
Lethargy 3 (2.8) 8 (7.8) 0.103
Confusion 0 0 NA
Seizure 0 0 NA
Numbness in hands or feet 2 (1.9) 1 (1.0) 1.000
Colon mucosal changes 2 (1.9) 3 (2.9) 0.677
Values are presented as number (%).
OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid, NA = not applicable, GI = gastrointestinal.
Table 6

Clinically abnormal laboratory findings after bowel preparation

jkms-39-e301-i006
Variables OST group (n = 108) 2 L-PEG/ASC group (n = 103) P value
Patients with clinically abnormal electrolytes 9 (8.3) 5 (4.9) 0.310
Sodium 7 (6.5) 0 0.014
Potassium 0 4 (3.9) 0.055
Chloride 2 (1.9) 1 (1.0) 1.000
Calcium 1 (0.9) 0 1.000
Magnesium 17 (15.7) 18 (17.5) 0.735
Phosphorus 20 (18.5) 12 (11.7) 0.164
Blood urea nitrogen 14 (13.0) 7 (6.8) 0.135
Creatinine 3 (2.8) 3 (2.9) 1.000
eGFR 2 (1.9) 3 (2.9) 0.677
Values are presented as number (%).
OST = oral sulfate tablet, 2 L-PEG/ASC = 2 L-polyethylene glycol plus ascorbic acid, eGFR = estimated glomerular filtration rate.

DISCUSSION

There have been various attempts to improve patient compliance with bowel cleansing such as reducing the total intake volume,89 removing sulfate from PEG,6 reducing the content of ascorbic acid in PEG solution,10 and using bowel preparation tablets.23 The oral sodium phosphate (OSP) tablet was developed to avoid poor taste and the ingestion of a very large volume of liquid of the existing preparations.23 The tablets showed better patient compliance and acceptability rates than PEG-based solutions.2425 However, the guidelines of the European Society of Gastrointestinal Endoscopy do not recommend the routine use of OSP due side effects including kidney injury.26
OSS is a hyperosmolar laxative that does not cause significant fluid or electrolyte shifts because it is a sulfate, a poorly absorbed anion, and was developed to reduce the amount of total intake compared to previous agents.2728 A randomized controlled trial (RCT) reported that successful bowel preparation was significantly more frequent in an OSS group than in a 4 L sulfate-free PEG group 21 and the adequate bowel preparation rate of the OSS group was not significantly different from that of the low-volume PEG group (93.3% vs. 90.6%, P = 0.16) in a meta-analysis of RCTs involving 2,049 subjects.12 OSS showed a satisfactory bowel cleansing efficacy that was noninferior to high- or low-volume PEG but did not significantly improve patient compliance compared to PEG. This is probably because the total amount of intake of OSS is not less than that of low-volume PEG, and nausea and vomiting are more frequent with OSS than with low-volume PEG. To maintain the bowel cleansing effect of OSS and improve patient compliance, OST, a tablet form of the preparation agent, was developed in 2020.13 In a phase 3 noninferiority trial, the successful bowel cleansing rate of an OST group (95.5%) was noninferior to that of an OSS group (98.2%). In addition, the OST group had fewer intraluminal bubbles (0.9% vs. 81.3%, P < 0.001) and lower incidences of nausea and vomiting, with better tolerability and willingness to repeat the regimen (76.8% vs. 41.6%, P < 0.001), than the OSS group. A RCT has compared OST and 2 L-PEG/ASC29; however, that work was based on a scale not typically used to assess bowel cleansing efficacy, and studies comparing these two bowel preparation agents are notably scarce. Therefore, we evaluated the bowel preparation efficacy of OST compared to 2 L-PEG/ASC using the validated BBPS15 and HCS14 and assessed tolerability and adverse events in a prospective multicenter RCT. The overall successful bowel cleansing rate of the OST group was noninferior to that of the 2 L-PEG/ASC group (BPPS; 90.7% vs. 91.3%, P = 0.895, HCS: 96.3% vs. 94.2%, P = 0.531), as reported previously (OST: 92.4% vs. 2 L-PEG:89.3%, P = 0.217).29 Based on the BBPS, OST was superior to 2 L-PEG/ASC in the right colon, as reported previously. However, the high-quality cleansing rate in the transverse colon and left colon based on the BBPS was superior in the OST group compared to the 2 L-PEG/ASC group. However, the high-quality cleansing rate evaluated using the HCS did not show a significant difference between the two groups. The discrepancy in the higher high-quality cleansing rates between the BBPS and HCS may have occurred because unlike the HCS, the BBPS evaluates cleansing after all retained fluid and foam have been flushed and suctioned. Because OST contains simethicone,13 the rate of intraluminal bubble formation was significantly lower in the OST group than in the 2 L-PEG/ASC group. A recent large-scale retrospective study showed that the ADR (34.5% vs. 30.7%, P < 0.001) and PDR (56.0% vs. 50.8%, P < 0.001) were higher with OST than with 2 L-PEG.30 By contrast, we did not find any significant differences in ADR and PDR between our two groups. In actual clinical practice, because simethicone is commonly prescribed and used together with 2 L-PEG/ASC, the rate of intraluminal bubble formation might not show a significant difference between the two bowel cleansing agents. Therefore, there could be a discrepancy between our study results and real-world clinical situations.
Compliance is important for successful bowel preparation. According to an RCT, experience consuming the preparation, overall experience, comparison with previous experience, and willingness to repeat colonoscopy with the same agent are significantly higher with OST than with 2 L-PEG.29 In our study, the scores for taste, ease, and amount of consumption of the preparation agent, and willingness to repeat colonoscopy with the same agent (89.8% vs. 78.6%, P = 0.026), were significantly higher with OST than with 2 L-PEG/ASC.
The OST group was expected to have fewer symptoms such as nausea and vomiting compared to the 2 L-PEG/ASC group due to its better tolerability. However, in a previous RCT comparing OST and 2 L-PEG/ASC, nausea (OST, 17.1% [48/281] vs. 2 L-PEG/ASC, 9.6% [26/271], P < 0.001) and vomiting (OST, 8.2% [23/281] vs. 2 L-PEG/ASC, 2.2% [6/271], P < 0.001) were less common in the 2 L-PEG/ASC group. Despite this, severe symptoms were rare, with only one case of severe nausea reported in the OST group (0.4%) and no cases of severe vomiting in either group.29
In our study, although the differences were not statistically significant, nausea and vomiting were slightly more frequently reported in the OST group compared to the 2 L-PEG/ASC group: nausea (28.7% vs. 20.4%, P = 0.161) and vomiting (5.6% vs. 1.0%, P = 0.120). Unfortunately, we did not assess the severity of these symptoms, and the limitation of using a yes/no questionnaire did not allow for a more detailed analysis. However, under the same conditions, there was no statistically significant difference between the two cleansing agents. Additionally, no cases of severe nausea or vomiting were observed that would have prevented the completion of the colonoscopy or required discontinuation of the bowel preparation.
Hyponatremia (Na < 135 mEq/L) is a relatively common condition with an incidence and prevalence of approximately 5% in adults. It can sometimes occur due to excessive water intake during bowel preparation. Symptoms such as apathy/agitation, fatigue, anorexia, nausea, headache, muscle cramps, tachycardia, oliguria/anuria, and confusion typically appear when sodium levels fall below 120 to 125 mmol/L.31 In our study, all 7 patients in the OST group with abnormal sodium levels had mild hyponatremia (130–134 mmol/L), specifically between 132 and 134 mEq/L, with no significant clinical symptoms. Additionally, there were no significant serious adverse events or changes in laboratory parameters in the OST group compared to the 2 L-PEG/ASC group. Therefore, we considered OST to be clinically safe.
With an aging society, the safety and effectiveness of bowel preparation in the elderly are increasingly important. In a previous study, among individuals aged ≥ 65 years, the BBPS score and satisfaction were significantly higher in OST group than in 2L-PEG group, but there were no significant differences in the rate of adverse events between the two groups.32
In our study, among patients ≥ 65 years of age, the BBPS scores, adverse event rates, and tolerability were not significantly different between OST and 2 L-PEG/ASC (Supplementary Table 1). However, most of the tolerability indicators—such as taste, ease of consumption, amount of the preparation agent consumed, and willingness to undergo repeat colonoscopy with the same agent—were better in the OST group than in the 2 L-PEG/ASC group. However, these results were not statistically significant, likely because of the small sample size. Hyponatremia was observed only in the OST group, affecting 3 (11.1%) patients (133 mEq/L in 2 patients and 134 mEq/L in 1 patient). All these sodium levels corresponded to mild hyponatremia, and no clinically significant symptoms were observed. In a recent RCT involving 254 patients aged ≥ 70 years, overall satisfaction and tolerability were significantly higher in the OST group than in the 2 L-PEG/ASC group. Additionally, no clinically significant differences in serum laboratory results, including sodium levels, were found between the 2 preparation agents. Additionally, most laboratory parameters outside the normal range remained within normal limits at the third and fourth visits.33
This study was not specifically designed for patients aged ≥ 65 years, and the subgroup analysis conducted for this age group is limited by the small sample size, which restricts the robustness of the comparison. Although the results were not statistically significant, the taste, ease, and amount of consumption of the preparation agent, as well as the willingness to repeat colonoscopy with the same agent, were better in the OST group compared to the 2 L-PEG/ASC group. In a larger RCT involving 254 patients aged ≥ 70 years, overall satisfaction and tolerability were significantly higher in the OST group compared to the 2 L-PEG/ASC group.
Further research with a larger population is needed to confirm these trends. There were no significant differences in the successful bowel cleansing rate between patients who had 6 to 9 bowel movements compared to those who had > 10 bowel movements (Supplementary Table 2).
This study had several limitations. The participation of multiple institutions introduces the potential for interobserver variability. In addition, we did not conduct gastric endoscopies, which prevented confirmation of an association between gastric mucosal damage and use of bowel preparation agents. Not comparing the laboratory test results before and after the administration of the bowel cleansing agents, and thus being unable to measure any significant changes from baseline or determine whether abnormal results returned to normal, is a limitation in assessing safety. However, no serious adverse effects were observed with either of the two bowel cleansing agents, and we instructed the patients to contact the hospital if any symptoms persisted. No patients needed to return to the hospital after the procedure.
However, this was a multicenter, prospective study that compared OST with 2 L-PEG/ASC using validated bowel preparation quality scales (the BBPS and the HCS). Our findings should help clinicians select the most effective and safe bowel preparation regimen.
In conclusion, OST was noninferior to 2 L-PEG/ASC in terms of bowel cleansing efficacy and showed better tolerability.

Notes

Funding: This work was supported by the Soonchunhyang University Research Fund (2023-0076).

Disclosure: The authors have no potential conflicts of interest to disclose.

Author Contributions:

  • Conceptualization: Jung Y, Kang HW, Park JJ, Kim HG.

  • Data curation: Jung Y, Yang DH, Baek DH, Chun J, Gweon TG, Goong HJ, Kwak MS, Lee HJ, Park SK, Lee JH, Kim HG.

  • Formal analysis: Jung Y.

  • Funding acquisition: Jung Y, Kim HG.

  • Investigation: Jung Y, Yang DH, Kang HW, Park JJ, Baek DH, Chun J, Gweon TG, Goong HJ, Kwak MS, Lee HJ, Park SK, Lee JH.

  • Methodology: Jung Y, Yang DH, Kang HW, Park JJ, Baek DH, Chun J, Gweon TG, Goong HJ, Kwak MS, Lee HJ, Park SK, Lee JH, Kim HG.

  • Resources: Kim HG.

  • Supervision: Kim HG.

  • Validation: Kim HG.

  • Visualization: Jung Y, Kim HG.

  • Writing - original draft: Jung Y.

  • Writing - review & editing: Kim HG.

References

1. Kim HM, Kim TI. Screening and surveillance for hereditary colorectal cancer. Intest Res. 2024; 22(2):119–130. PMID: 38311713.
2. Kim SY, Kwak MS, Yoon SM, Jung Y, Kim JW, Boo SJ, et al. Korean Guidelines for Postpolypectomy Colonoscopic Surveillance: 2022 revised edition. Intest Res. 2023; 21(1):20–42. PMID: 36751043.
3. Sekiguchi M, Matsuda T, Hotta K, Saito Y. Post-polypectomy surveillance: the present and the future. Clin Endosc. 2022; 55(4):489–495. PMID: 35811404.
4. Hong SW, Byeon JS. Endoscopic diagnosis and treatment of early colorectal cancer. Intest Res. 2022; 20(3):281–290. PMID: 35916019.
5. Davis GR, Santa Ana CA, Morawski SG, Fordtran JS. Development of a lavage solution associated with minimal water and electrolyte absorption or secretion. Gastroenterology. 1980; 78(5 Pt 1):991–995. PMID: 7380204.
6. DiPalma JA, Marshall JB. Comparison of a new sulfate-free polyethylene glycol electrolyte lavage solution versus a standard solution for colonoscopy cleansing. Gastrointest Endosc. 1990; 36(3):285–289. PMID: 2365214.
7. Rivas JM, Perez A, Hernandez M, Schneider A, Castro FJ. Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy. World J Gastroenterol. 2014; 20(30):10620–10627. PMID: 25132784.
8. Xie Q, Chen L, Zhao F, Zhou X, Huang P, Zhang L, et al. A meta-analysis of randomized controlled trials of low-volume polyethylene glycol plus ascorbic acid versus standard-volume polyethylene glycol solution as bowel preparations for colonoscopy. PLoS One. 2014; 9(6):e99092. PMID: 24902028.
9. Maida M, Macaluso FS, Sferrazza S, Ventimiglia M, Sinagra E. Effectiveness and safety of NER1006 versus standard bowel preparations: a meta-analysis of randomized phase-3 clinical trials. Dig Liver Dis. 2020; 52(8):833–839. PMID: 32586765.
10. Jung Y, Kang SB, Yoon HJ, Cha JM. Improving the tolerability and safety of 1-L polyethylene glycol plus low-dose ascorbic acid for bowel preparation in a healthy population: a randomized multicenter clinical trial. Gastrointest Endosc. 2022; 96(2):341–350.e1. PMID: 35288148.
11. Yang HJ, Park SK, Kim JH, Im JP, Yeom DH, Seo GS, et al. Randomized trial comparing oral sulfate solution with 4-L polyethylene glycol administered in a split dose as preparation for colonoscopy. J Gastroenterol Hepatol. 2017; 32(1):12–18. PMID: 27349220.
12. Ali IA, Roton D, Madhoun M. Oral sulfate solution versus low-volume polyethylene glycol for bowel preparation: meta-analysis of randomized controlled trials. Dig Endosc. 2022; 34(4):721–728. PMID: 34784082.
13. Yang HJ, Park DI, Park SK, Lee CK, Kim HJ, Oh SJ, et al. Novel sulfate tablet PBK-1701TC versus oral sulfate solution for colon cleansing: a randomized phase 3 trial. J Gastroenterol Hepatol. 2020; 35(1):29–36. PMID: 31396995.
14. Halphen M, Heresbach D, Gruss HJ, Belsey J. Validation of the Harefield Cleansing Scale: a tool for the evaluation of bowel cleansing quality in both research and clinical practice. Gastrointest Endosc. 2013; 78(1):121–131. PMID: 23531426.
15. Calderwood AH, Schroy PC 3rd, Lieberman DA, Logan JR, Zurfluh M, Jacobson BC. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness. Gastrointest Endosc. 2014; 80(2):269–276. PMID: 24629422.
16. Ell C, Fischbach W, Bronisch HJ, Dertinger S, Layer P, Rünzi M, et al. Randomized trial of low-volume PEG solution versus standard PEG + electrolytes for bowel cleansing before colonoscopy. Am J Gastroenterol. 2008; 103(4):883–893. PMID: 18190651.
17. Bitoun A, Ponchon T, Barthet M, Coffin B, Dugué C, Halphen M. Norcol Group. Results of a prospective randomised multicentre controlled trial comparing a new 2-L ascorbic acid plus polyethylene glycol and electrolyte solution vs. sodium phosphate solution in patients undergoing elective colonoscopy. Aliment Pharmacol Ther. 2006; 24(11-12):1631–1642. PMID: 17094774.
18. Tajika M, Niwa Y, Bhatia V, Kondo S, Tanaka T, Mizuno N, et al. Can mosapride citrate reduce the volume of lavage solution for colonoscopy preparation? World J Gastroenterol. 2013; 19(5):727–735. PMID: 23430381.
19. Arya V, Gupta KA, Valluri A, Arya SV, Lesser ML. Rapid colonoscopy preparation using bolus lukewarm saline combined with sequential posture changes: a randomized controlled trial. Dig Dis Sci. 2013; 58(8):2156–2166. PMID: 23456498.
20. Matro R, Shnitser A, Spodik M, Daskalakis C, Katz L, Murtha A, et al. Efficacy of morning-only compared with split-dose polyethylene glycol electrolyte solution for afternoon colonoscopy: a randomized controlled single-blind study. Am J Gastroenterol. 2010; 105(9):1954–1961. PMID: 20407434.
21. Rex DK, Di Palma JA, Rodriguez R, McGowan J, Cleveland M. A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy. Gastrointest Endosc. 2010; 72(2):328–336. PMID: 20646695.
22. Koo JS, Byeon JS, Lee BI, Jung SA, Kim TI, Jeen YT. Efficacy and safety of TJP-008 compared to 2 L PEG with ascorbate in colon cleansing: a randomized phase 3 trial. Gut Liver. 2022; 16(2):259–268. PMID: 34810296.
23. Aronchick CA, Lipshutz WH, Wright SH, Dufrayne F, Bergman G. A novel tableted purgative for colonoscopic preparation: efficacy and safety comparisons with Colyte and Fleet Phospho-Soda. Gastrointest Endosc. 2000; 52(3):346–352. PMID: 10968848.
24. Lee SW, Bang CS, Park TY, Suk KT, Baik GH, Kim DJ. Split-dose bowel preparation for colonoscopy: 2 liters polyethylene glycol with ascorbic acid versus sodium picosulfate versus oral sodium phosphate tablets. Korean J Gastroenterol. 2017; 70(2):89–95. PMID: 28830134.
25. Cheng J, Tao K, Shuai X, Gao J. Sodium phosphate versus polyethylene glycol for colonoscopy bowel preparation: an updated meta-analysis of randomized controlled trials. Surg Endosc. 2016; 30(9):4033–4041. PMID: 26679172.
26. Hassan C, East J, Radaelli F, Spada C, Benamouzig R, Bisschops R, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy. 2019; 51(8):775–794. PMID: 31295746.
27. Di Palma JA, Rodriguez R, McGowan J, Cleveland M. A randomized clinical study evaluating the safety and efficacy of a new, reduced-volume, oral sulfate colon-cleansing preparation for colonoscopy. Am J Gastroenterol. 2009; 104(9):2275–2284. PMID: 19584830.
28. Nam JH, Hong SB, Lim YJ, Lee S, Kang HW, Kim JH, et al. Comparison of oral sulfate solution and polyethylene glycol plus ascorbic acid on the efficacy of bowel preparation. Clin Endosc. 2020; 53(5):568–574. PMID: 32336051.
29. Di Palma JA, Bhandari R, Cleveland MV, Mishkin DS, Tesoriero J, Hall S, et al. A safety and efficacy comparison of a new sulfate-based tablet bowel preparation versus a PEG and ascorbate comparator in adult subjects undergoing colonoscopy. Am J Gastroenterol. 2021; 116(2):319–328. PMID: 33165006.
30. Song JH, Bae JH, Yim JY. Efficacy of oral sulfate tablets for bowel preparation and adenoma detection rate. J Gastroenterol Hepatol. 2023; 38(3):410–415. PMID: 36453642.
31. Filippatos TD, Makri A, Elisaf MS, Liamis G. Hyponatremia in the elderly: challenges and solutions. Clin Interv Aging. 2017; 12:1957–1965. PMID: 29180859.
32. Kim JH, Park YE, Kim TO, Park J, Oh GM, Moon W, et al. Comparison of the efficacy and safety between oral sulfate tablet and polyethylene glycol for bowel preparation before colonoscopy according to age. Medicine (Baltimore). 2022; 101(27):e29884. PMID: 35801801.
33. Kang HS, Na SY, Yoon JY, Jung Y, Seo GS, Cha JM. Efficacy, tolerability, and safety of oral sulfate tablet versus 2 L-polyethylene glycol/ascorbate for bowel preparation in older patients: prospective, multicenter, investigator single-blinded, randomized study. J Gastroenterol. 2024; 59(5):402–410. PMID: 38492010.

SUPPLEMENTARY MATERIALS

Supplementary Table 1

Bowel preparation efficacy, tolerability, and safety among patients ≥ 65 years of age
jkms-39-e301-s001.doc

Supplementary Table 2

Relationship between the number of bowel movements after preparation and clinical significance
jkms-39-e301-s002.doc

Supplementary Fig. 1

Reference material for the assessment of bowel preparation quality.
jkms-39-e301-s003.doc
TOOLS
Similar articles