ORIGINAL PAPER
Nagoya J. Med. Sci. 83. 787–799, 2021
doi:10.18999/nagjms.83.4.787

Split-dose low-volume polyethylene glycol is non-inferior but
less preferred compared with same-day bowel preparation
for afternoon colonoscopy
Masahiro Tajika1, Tsutomu Tanaka1, Makoto Ishihara1, Yutaka Hirayama1,
Sachiyo Onishi1, Nobumasa Mizuno2, Takamichi Kuwahara2,
Nozomi Okuno2, Shinpei Matsumoto2, Kazuhiro Toriyama2,Masahiro Obata2, Yusuke Kurita2, Shinya Kondo3, Kazuo Hara2,
Vikram Bhatia4, Masahiko Ando5 and Yasumasa Niwa1
1
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan3
Department of Gastroenterology, Aichi Cancer Center Aichi Hospital, Okazaki, Japan
4
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
5
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
2

ABSTRACT
Currently, the same-day polyethylene glycol-electrolyte lavage solution (PEG-ELS) regimen is particularly recommended for afternoon colonoscopy as an alternative to the split-dose regimen in westerncountries. However, in Japan, the split-dose regimen has never been used as a standard colonoscopy
preparation regimen. The aim of this study was to compare the efficacy and tolerability of split-dose PEG
containing ascorbic acid (ASC) with same-day single dose PEG-ASC in Japan.This was a single-blinded,
non-inferiority, two-center, randomized, controlled study. In-hospital patients were randomized to the sameday regimen or the split regimen using a web-based registry system. The same-day group was instructed
to take 5 mL of sodium picosulfate in the evening, and on the day of the colonoscopy, they took 1.5 L
of PEG-ASC. The split group was instructed to take 1 L of PEG-ASC before the day of colonoscopy,
followed by another 1 L of PEG-ASC on the day of colonoscopy. Bowel cleansing was evaluated by the
Boston Bowel Preparation Scale.A total of 153 patients were randomized to either the same-day group(n=78, males 60.0%, mean age 62.7 years) or the split group (n=75, 61.3%, 61.9 years). The rates ofsuccessful bowel cleansing were 83.3% in the same-day group vs. 92.0% (83.4%–97.0%) in the split
group, P=0.10). No serious adverse events occurred in the study population. However, more patients in thesame-day group were willing to repeat the same preparation regimen (P<0.001). The split-dose regimen
was not inferior to the same-day regimen with respect to the efficacy of bowel preparation, but the patients
preferred the same-day regimen.
Keywords: afternoon colonoscopy, bowel preparation, split-dose
Abbreviations:
PEG-ELS: polyethylene glycol-electrolyte lavage solution
ASC: ascorbic acid

Received: January 26, 2021; accepted: April 6, 2021
Corresponding Author: Masahiro Tajika, MD, PhD
Department of Endoscopy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681,
Japan
Tel: +81-52-762-6111, Fax: +81-52-763-5233, E-mail: mtajika@aichi-cc.jp
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PEG-ASC: polyethylene glycol-electrolyte lavage solution containing ascorbic acid
PICO: picosulfate solution
This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

INTRODUCTION
Appropriate bowel preparation is essential for precise detection of colorectal neoplasms.1,2
Inadequate bowel preparation is related to a lower adenoma detection rate, longer procedure
time, patient discomfort, and increased costs because of the need for repeat procedures.3-6 Anappropriate purgative type, volume, and timing of administration are needed to achieve sufficientbowel cleansing and patient tolerability.7-9 Split-dose regimens, defined as drinking about half ofthe cleansing solution over two days, regardless of purgative type or volume, have been shown
to improve colonic cleanliness, the adenoma detection rate, and patient tolerability compared with
day-before regimens, and they have thus been recommended as a standard bowel preparation
regimen in western countries.10-13 Recently, especially for patients with an afternoon colonoscopy,
same-day regimens are also recommended as an effective alternative to split-dose regimens.12,13
On the other hand, in Japan, same-day bowel preparation is commonly used for colonoscopy.
The Japan Gastroenterological Endoscopy Technicians Society conducted a questionnaire survey
in Japan, from August 2015 to February 2016, to investigate the bowel preparation practices forcolonoscopy in 1,814 Japanese institutions [unpublished data]. All institutions contacted in thissurvey performed same-day preparation, with the most preferred bowel preparation regimen being
PEG-ELS (45.1%), followed by PEG + ascorbic acid (ASC) (35.8%), magnesium citrate (17.8%),
and 86.5% of them took an adjunctive agent such as sodium picosulfate solution (PICO) in theevening of the day before colonoscopy.
PEG-ASC, (Moviprep®, EA Pharma Co., Ltd., Tokyo, Japan) has been available in Japan
since June 2013. A phase III trial evaluated the efficacy, tolerability, and safety of PEG-ASC
compared with standard PEG-ELS without dietary restriction or laxatives.14 In this study, theoptimal colonoscopy preparation required 1.63 ± 0.38 L PEG-ASC. The addition of ASC reduced
the volume of lavage solution with comparable efficacy and better tolerability than standard
PEG-ELS. We demonstrated that the 1.5-L PEG-ASC regimen was better accepted by patients
than the 2-L PEG-ELS,15 with similar tolerability, bowel cleansing, and safety between regimens.
Based on these results, same-day 1.5 L PEG-ASC and PICO the previous evening have become
the standard colonoscopy preparation regimen in our hospital, and it is one of the most preferredregimens in Japan. However, in our subsequent study comparing how to take PEG-ASC, therates of successful cleansing and patient acceptability of the same-day 1.5 L PEG-ASC regimen
were 71.1% and 77.5%, respectively, which were not satisfactory.16 A more effective colonoscopy
preparation regimen is needed to improve efficacy and patient tolerability.
Although same-day regimens and split regimens showed similar bowel cleansing efficacy
and overall tolerability, only for trials using the purgative type of PEG-ELS or PEG-ASC,the cleansing efficacy of split-regimens was better, though not significantly, than of same-day
regimens.17-19 Furthermore, for patient tolerance, one study showed less nausea and vomiting insplit-regimens.19 Despite the lower volume (1.5 L) of PEG-ASC, the necessity to drink such alarge amount of liquid with an unacceptable taste followed by 0.75 L of clear liquid within about
2 hours has a negative impact on patient compliance. If the pretreatment were divided into twodays, the impact may decrease. Therefore, we decided to compare the Western standard regimen,
the split-dose regimen, with the Japanese standard regimen. We hypothesized that the split-dose
regimen is as effective as the same-day regimen in cleansing efficacy, and, furthermore, that the789
Split-dose colonoscopy preparation

split-dose regimen has better patient tolerability in Japanese patients. The purpose of this study
was to compare the efficacy and tolerability of split-dose 2 L PEG-ASC with same-day single
dose 1.5 L PEG-ASC and 5 mL of PICO.

PATIENTS AND METHODS
The study was conducted at Aichi Cancer Center Hospital, Nagoya, and Aichi Hospital, Aichi
Cancer Center Hospital, Okazaki from September 2016 to March 2018. This was a prospective,
investigator-blinded, two-center, non-inferiority, randomized comparison of the same-day regimenof 1.5 L PEG-ASC + 5 mL PICO the day prior and the split-dose regimen of 2 L PEG-ASC
in patients scheduled for colonoscopy. All included patients provided written, informed consent
for inclusion. The ethics committees of both participating hospitals approved the study, which
was registered with an international clinical trial registry (UMIN000023895).
All consecutive patients aged 20 years old and over scheduled for treatment colonoscopies
such as polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection at eachhospital were eligible to participate. The exclusion criteria were: patients with severe comorbidities(cardiac, renal, hepatic, or metabolic disease, ascites, etc.), patients with severe constipation (<2bowel movements per week), patients with an allergy to PEG-ELS, patients with a history ofgastric stapling or bypass procedure, or patients with a history of colorectal surgery.

METHODS
Randomization and blinding
The Pocock and Simon minimization method was used to perform the randomization tobalance sex, age (<70 years or ≥70 years), and institution between the two groups.20 A computergenerated, random-number list allocated patients to receive one of the two alternative bowel
preparation regimens. Allocation concealment was ensured by an independent research assistantusing a reputable web-based registry system managed by the Data Center of Nagoya University
Hospital, Nagoya, Japan. Patients were randomized on the day when hospitalization was decided,
and the independent research assistant entered each chosen regimen, which was then registeredin the clinical pathway using an electronic medical record. Only the research assistant and thenurses in the ward could know how they were assigned.
Everyone who participated in this study, including endoscopists and endoscopy nurses, wereblinded to treatment group. Patients were instructed not to discuss their bowel preparation withanyone other than the research assistant by a ward nurse. Comparisons between the same-day
group and the split-dose group were made in an investigator-blinded fashion.
Bowel preparation methods (Fig. 1)
All patients were admitted to each hospital the day before colonoscopy. When patients were
hospitalized, their ward nurses gave them an orientation talk about the assigned regimen. The
ward nurse carefully explained how the product should be taken, emphasizing the importanceof complete intake of the solution for a safe and reliable procedure, using easy-to-understandinstructions. They were also instructed to eat a low-residue diet served in each hospital. The
same-day group was asked to drink more than 1 L of clear liquid the day before colonoscopy,
and instructed to take 5 mL of PICO 0.75%; (Laxoberon®: Teijin Pharma, Ltd., Tokyo, Japan)
in the evening (at 9–10 pm). On the day of the colonoscopy, they received 1.5 L of PEG-ASC

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Fig. 1 The study schedule
PEG-ASC: polyethylene glycol electrolyte lavage solution containing ascorbic acidconsisting of 100.0 g macrogol 4000, 7.5 g sodium sulfate, 2.7 g sodium chloride, 1.0 g potassium chloride, 4.7 g ascorbic acid, 5.9 g sodium ascorbate, and lemon flavoring per each liter.
They were instructed to drink the first 1 L of cleansing solution followed by 0.5 L of clear
fluids at a rate of 0.25 L every 15 min from 9 am. After that, they were instructed to drink
the remaining 0.5 L of cleansing solution followed by 0.25 L of clear fluids at the same rateby 11:15 am. The split-dose group was instructed to take 1 L of PEG-ASC followed by 0.5 L
of clear liquids at a rate of 0.25 L every 15 min between 4 pm and 5.30 pm the day before
colonoscopy, followed by another 1 L of PEG-ASC followed by 0.5 L of clear liquids at a
rate of 0.25 L every 15 min between 9.45 am and 11:15 am on the day of colonoscopy. Allcolonoscopies were scheduled to be performed after 2 pm.
Evaluation of bowel preparation
Efficacy of bowel preparation was assessed by an endoscopist blinded to patient allocation
using the Boston Bowel Preparation Scale (BBPS), on a 4-point scale (0–3) per colonic segment (right, transverse, and left colon).21 Segment scores were summed to calculate the scoresof each of the three segments, ranging from 0–9. ‘Successful’ bowel preparation was defined
as total score of 6 or more, and all segment scores were 2 or more; others were considered‘failed’ bowel preparation. The ward nurses checked patients’ excretions within 1 hour after
finishing the preparation on the day of colonoscopy. If solid stool with muddy excretions or
no excretion was seen at that time, the patient was given an additional preparation, such as anadditional 0.5 L of PEG-ELS or an enema.16 In Japan, in cases of poor preparation, an enema
is often given to promote defecation. Patients who received additional preparation were also

791
Split-dose colonoscopy preparationconsidered to have ‘failed’ bowel preparation. In this study, all of the procedures were performedby experienced endoscopists, all of whom had performed more than 1,000 colonoscopies. As
described in a previous study,16 each endoscopist performed calibration exercises involving morethan 20 colonoscopies before the start of the study, based on their interpretation of the agreed
upon scale anchors, to ensure concordance.
As one of the indicators of bowel cleansing effect, the disappearance of the mucus-surroundedgas bubbles in the colonic lumen was evaluated using the optimal visibility grade.22 The overallmucosal visibility was graded using the following 3-grade scale: optimal was clear imaging withno or minimal amount of bubbles or foams that could be easily removed (grade 0); adequate
was a modest amount of bubbles and foams that could be cleared within a minimal amount oftime (grade 1); and insufficient was the presence of foam and bubbles that significantly reduced
clear visualization of the mucosa (grade 2). Mucosal visibility was assessed in a pre-washingprocedure before evaluation of BBPS.
Patient measurements
All patients were asked by ward nurses or the research assistant to complete a questionnaire
immediately before the procedure to evaluate preparation completion, tolerability, adverse events,
sleep quality, and willingness to repeat the same regimen. They were also asked to record thetime and number of bowel movements from the start of ingestion to the appearance of clear
excretion. Patient tolerability was measured by the patient’s perceived ease or difficulty in taking
the preparation on a 4-grade scale. Sleep quality was evaluated using a 4-grade scale according tosleep comfort and sleep disturbances due to the preparation during the night before colonoscopy
compared to a usual day. Adverse events were defined by the degree of gastrointestinal symptoms
such as nausea, vomiting, abdominal distension, and pain. These symptoms were scored on a
4-grade scale. Willingness to repeat the same regimen was also scored on a 4-grade scale.
Outcome measures
The primary end point of this study was demonstrating the non-inferiority of the split-dose
regimen compared to the same-day regimen for successful bowel cleansing. The secondary end
points were preparation completion, tolerability, adverse events, sleep quality, willingness to repeat
the same regimen, and the rate of optimal mucosal visibility (score 0).
Statistical analysis
On the basis of data from a previous study,16 the successful bowel cleansing rate with thesame-day regimen was estimated to be 71.0%. It was expected that about 81.0% of the split-dosegroup would show adequate successful bowel cleansing, and the non-inferiority margin was set at–10%. This study was designed to have 80% power to establish non-inferiority (using a one-sided
test with alpha of 0.025 and a target sample size of 72 per group). It was decided to enroll
more than 150 patients to allow for an approximate drop-out rate of 5%. The primary analysis
for non-inferiority was performed on the intention-to-treat population. Per-protocol analysis was
performed in patients who did not receive additional treatment.
Descriptive statistics are presented as means ± standard deviation (SD) or as the number ofpatients (%). The two-sided t-test was used to compare the means of continuous variables; thelikelihood ratio chi-squared test was used to compare categorical measures. The Mantel extension
test adjusted for age and sex was applied to compare clinical outcomes between the two groups.
Categorical variables were compared using the Mantel extension test. P values < 0.05 wereconsidered significant. All analyses were performed using SAS version 9.4 (SAS Institute, Cary,NC) at the Data Center of Nagoya University Hospital, Nagoya, Japan.

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RESULTS
Patients’ characteristics
From September 2016 to March 2018, 155 patients were screened for study inclusion, and all
patients were randomized into two groups. Two patients in the split-dose group were excluded
due to other disease or an accident (Fig. 2). Table 1 shows the baseline characteristics of thepatients. There were no significant differences between the two groups.

Fig. 2

Table 1

Variable
No. of patientsAge (y), mean±SD

Patient flow

Patients’ characteristics

Standard group

Split group7875

62.7 ± 9.9

61.9 ± 11.1

P value
0.63

Male/female

47/31

46/29

0.89

Height (cm)

162.8 ± 9.9

162.8 ± 9.1

0.98

62.4 ± 13.7

62.7 ± 13.2

0.87

Weight (kg)Body mass index (kg/m )23.4 ± 3.7

23.5 ± 3.1

0.81

Average sleeping time (h)6.69 ± 1.14

6.49 ± 1.08

0.27

Bowel habit (daily) (n, %)62 (79.5)

57 (74.0)

0.49

2

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Bowel cleansing efficacy and endoscopic findings (Table 2)Time to first defecation after the start of ingestion of bowel preparation was shorter in thesame-day group compared with Day 1 in the split-dose group (P<0.001). In the split-dose group,
the time to first defecation was shorter on Day 2 than on Day 1 (P<0.001) (Fig. 3). The frequency
of defecation was lower on Day 2 in the split-dose group compared with the same-day group(P<0.01). Time to preparation was not significantly different between the same-day group andDay 2 of the split-dose group. The average time to last defecation before going to bed after thestart of ingestion (4 pm) of bowel preparation was 281.7 minutes (around 9 pm; 95% confidence
interval [CI] 262.4–300.9 minutes) (Fig. 4).

Table 2

Results of preparation and endoscopic findings
Standard

Variable
No. of patients

Split group
Day 1

Day 2

P value

56.2 ± 23.1

59.1 ± 27.6

<0.001*

78

77

Time to take the solution (min)115.3 ± 56.7

Time to first defecation (min, mean±SD)54.8 ± 34.2

91.1 ± 56.3

47.1 ± 26.2**

0.12*

Frequency of defecation (times, mean±SD)12.4 ± 4.3

6.8 ± 4.0

10.1 ± 4.7**<0.01*

Time to preparation (min, mean±SD)198.1 ± 93.8

175.9 ± 82.9

0.12*

233 ± 118

0.82*

Time to last defecation before going to bed

281.7 ± 83.5

Preparation scale of last defecation (day 1)(watery clear/clear/muddy/soft stool/normal)
Elapsed time from last fluid intake to(18/40/14/1/1)
229 ± 115

colonoscopy (min, mean+SD)
Cecal intubation rate (n,%)

78 (100)

77 (100)

Insertion time (min, mean±SD)

8.8 ± 6.0

9.6 ± 5.5

0.41

Feeling of peristalsis (n, %)15 (19.2)

12 (16.0)

0.60

Optimal visibility grade (0/1/2)

45/24/9

39/19/17

0.17

2.1 ± 1.0

2.1 ± 0.7

0.67

BBPS (PP)Right colon (mean±SD)
Transverse colon (mean±SD)

2.3 ± 1.0

2.5 ± 0.6

0.12

Left colon (mean±SD)

2.4 ± 1.0

2.6 ± 0.6

0.04

Successful bowel cleansing (n, %)***

65 (83.3)

69 (92.0)

0.10

No. with additional PEG intake or enema(n, %)

9 (11.5)

1 (1.3)0.01

BBPS: Boston bowel preparation scale
PP: per-protocol analysis* Same-day group vs. split-dose group (Day 2).
** P<0.001, split-dose group (Day 1) vs. split-dose group (Day 2).
*** Difference and 95% confidence interval in the successful bowel preparation rate between thesame-day group and the split-dose group was 8.7% (–1.6% to 19.0%).

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Fig. 3 Distribution of time to first bowel movement
The time to first defecation after the start of ingestion of bowel preparation was shorter in the same-day groupcompared with Day 1 of the split-dose group (P<0.001). In the split group, the time to first defecation was
shorter on Day 2 compared with Day 1 (P<0.001).

Fig. 4 Time to last bowel movement before sleep (split-dose group only)
The average time to last defecation before going to bed after the start of ingestion (4 pm) of bowel preparation
was 281.7 minutes.

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There was no significant difference between the same-day group (83.3%; 73.2%–90.8%) andthe split-dose group (92.0%; 83.4%–97.0%) in the successful bowel preparation rate. The lower
limit of the 95%CI of the difference in proportions between two groups was –1.6%, which was
higher than the non-inferiority margin of –10%. In other words, the split-dose regimen was notinferior to the same-day regimen. The rate of patients who required additional preparation was
higher in the same-day group (11.5%) than in the split-dose group (1.3%) (P=0.01).
There were no significant differences in the mean total BBPS score between the two groups.
However, in the left colon, the mean BBPS score was significantly higher in the split-dose group(2.4 vs. 2.6; P=0.04).
Patient questionnaire
There was no difference in complete intake of the bowel cleansing solution between thetwo groups (Table 3). In terms of sleep quality of the day before colonoscopy, there were nodifferences between the two groups in average time, sleep disturbances, number of times waking
up for evacuation, and degree of sleeping. Although no serious adverse events occurred, the rateof vomiting tended to be higher in the same-day group and the rate of toilet accidents tended
to be higher in the split-dose group (P=0.05, respectively).
With respect to patient preference, the rate of willingness to repeat the same regimen was
higher for the same-day group than for the split-dose group (77% vs. 47%; P<0.001).

Table 3

Patient tolerance and acceptanceStandard

Variable
No. of patients

Split group
Day 1

78

Day 2

P value

72 (96.0)

0.75*

75

100% intake of solution (n,%)

72 (92.3)

66 (88.0)

Average sleeping time of Day 1 (h)6.6 ± 1.6

6.5 ± 1.4

0.80

Did the evacuation disturb your sleep?
Yes (n,%)20 (26.0)

19 (26.4)

0.95

No. of times got up for evacuation

1.9 ± 0.91

2.4 ± 1.6

0.27

Could you sleep well compared to usual
day? (well/fair/difficult/very difficult) (%)(18/44/30/8)(14/47/36/3)

0.95

Did you feel hungry in the night time ofday 1? (none/mild/moderate/severe) (%)(34/37/25/4)(34/41/21/4)

0.76(41/43/8/8)(37/40/15/8)

0.47(87/6/6/1)(88/7/4/1)

0.74(75/5)(100/0)0.05(31/36/26/7)(36/36/20/8)

0.67(87/10/3/0)(87/8/5/0)

0.66

How easy/difficult to take preparation?
(easy/fair/difficult/very difficult) (%)
Any symptoms (%)
Nausea(none/mild/moderate/severe)
Vomiting(no/yes)Distension(none/mild/moderate/severe)
Abdominal pain
(none/mild/moderate/severe)796
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Toilet accident (eg, wet one’s pants etc.)(no/attempt/yes) (%)(87/9/4)(77/13/10)

0.05(32/45/15/8)(20/27/30/23)

P<0.001

Willingness to repeat
the same preparation regimen (%)(yes/yes, if anything/no, if anything/no)* Same-day group vs. split-dose group (Day 2).

DISCUSSION
In Japan, the same-day PEG-ELS regimen with some laxatives such as PICO the previous
evening has traditionally been used for colonoscopy preparation. This is the first study to evaluate
the efficacy and tolerability of the split-dose regimen compared to the same-day regimen in
Japan. The present results showed that the split-dose regimen was non-inferior to the same-day
regimen in terms of bowel cleansing. Although patient tolerance was similar between the twogroups, patients were more willing to repeat the same-day regimen.
Recently, two large meta-analyses compared the efficacy and tolerability of split-dose andsame-day regimens.23,24 In the first report,23 484 studies were retrieved, with 14 trials meeting
inclusion criteria. The results showed that the rate of patients receiving same-day regimens andsplit-dose regimens with adequate preparation in the pooled analysis were 79.4% and 81.7%,
respectively, with no significant differences in 11 trials (OR 0.92, 95%CI 0.62–1.36). In terms ofpatient tolerance, willingness to repeat the regimen, plus completion of bowel preparation fluid
intake, did not differ significantly between regimens (OR 1.08, 0.45–2.61; OR 0.89, 0.45–1.78,
respectively). In another report,24 1216 studies were retrieved with 15 trials meeting inclusion
criteria. The results showed that the categorical outcome of high-quality bowel preparation forany same-day regimen versus any split-dose regimen did not differ, with adequate preparationin the pooled analysis of 76.2% and 80.2%, respectively, and no significant differences in 11
trials. Willingness to repeat and tolerability/compliance were similar (RR 1.14, 0.96–1.36; RR
1.00, 0.96–1.04, respectively) between regimens. Adverse events were similar except for bloating,which was less frequent in the same-day group. However, both studies included heterogeneity
in study design of component trials. In addition to the difference of purgatives, including
PEG, PEG-ASC, sodium phosphate, and magnesium citrate, etc., with various dosages in bothregimens, there were different methods of preparation, such as diet during preparation, the lengthof time for diet restriction, and use of laxatives. In this study, split-dose 2-L PEG-ASC wascompared with same-day single-dose 1.5-L PEG-ASC with 5 mL of PICO. The difference of
0.5 L of PEG-ASC, regardless of the additional use of PICO in the same-day group, may have
led to better outcomes for cleansing efficacy in the left colon and the low rate of additional
preparation in the split-dose group; however, time to first defecation after the start of ingestionof bowel preparation was significantly shorter on Day 2 compared with Day 1 in the split-dosegroup, and the total frequency of defecation during two days was significantly higher in the
split-dose group. Day 1 intake of PEG-ASC may boost defecation on Day 2. Although patientswith severe constipation were excluded in this study, the booster effect of PEG-ASC the day
before colonoscopy may lead to successful bowel preparation for these patients. Furthermore,
the cleansing efficacy of the same-day regimen in this study improved from 71.1% to 83.3%
compared to a previous study.16 We think that one of the reasons was the difference between
outpatients and inpatients. Although the cleansing efficacy did not differ between the two groups,
the split-dose regimen may become an option for patients with poor defecation who required

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additional preparation on previous examinations.
As for patient tolerance, there were no significant differences between the two groups. However, the number with vomiting was higher in the same-day group, and the number with toilet
accidents such as fecal incontinence was higher in the split-dose group. In the same-day group,
patients must ingest 2.25 L (1.5 L PEG-ASC + 0.75 L clear liquid) within 135 minutes. In the
split-dose group, the total dose each day was 1.5 L (1 L PEG-ASC + 0.5 L clear liquid). The
difference in the amount of liquid may lead to vomiting in the same-day group. Toilet accidents
may be related to the shorter time to first defecation on Day 2.
In planning this study, when patients in the split-dose group should start taking PEG-ASC toavoid sleep disturbance on Day 1 was considered. Previous studies reported that patients usingsame-day regimens had better sleep quality compared with those using split-dose regimens17,18;
therefore, it was decided that patients should start taking PEG-ASC from 4 pm (before a meal)
to decrease sleep disturbances, nausea, and vomiting. It was found that early intake of PEGASC succeeded in making no significant difference in sleep quality between the two groups. Ina meta-analysis,23 same-day regimens had better sleep quality than split-dose regimens. One of
the reasons why split-dose regimens interfered with sleep may be that the time to start taking
purgatives was late, from 6 pm to 9 pm. In the present study, with respect to the time to lastdefecation before sleep, 80% of patients completed the last defecation by 10 pm. Thus, it may
be possible that the time to start taking PEG-ASC could be delayed 2 or 3 hours (to 6 to 7pm). Furthermore, we served a low-residue diet after Day 1 of PEG-ASC intake. There was also
concern about eating a diet after taking PEG-ASC in planning this study, which did not affectthe efficacy of bowel cleansing or patient tolerance. Although various ways to improve patient
tolerability in split-dose regimens were tried, the willingness to repeat the same regimen was
significantly lower in the split-dose group. One of the reasons may be that all patients in thisstudy underwent the same-day regimen on previous occasions before this study, so they werereluctant to take PEG-ASC over 2 days. From the perspective of patient tolerability, split-dose
regimens may be appropriate for patients who have vomited with previous preparations or patients
who think that they cannot drink more than 1.5 L of cleansing solution and about 1 L of waterin several hours. Furthermore, since the time to first defecation and time to preparation on the
day of the colonoscopy was shorter in the split-dose regimen, a split-dose regimen may be usefulfor morning colonoscopy in the future.
There are some limitations in this study. First, this study was conducted in an inpatientsetting to ensure patient safety and to maximize compliance, because it was the first trial ofa split-dose regimen in Japan. However, this approach minimized bias and provided high rates
of good bowel preparation in both groups. Second, in the same-day group, an adjunctive agent
such as PICO was given the day before colonoscopy. Strictly speaking, it was not a same-day
regimen. However, it was common to give laxatives the day before colonoscopy in Japan, so thisstudy was conducted in a form suitable for practice. Third, this study included only Japanesepatients. Body composition and size of Asian populations are different from those of Western
populations. Therefore, the result of the current study may not be applicable to Western countries’
populations. Fourth, the adenoma detection rate was not evaluated, because endoscopic treatment
was planned for the inpatients in this study.

CONCLUSION
The split-dose regimen of 2-L PEG-ASC was not inferior to the same-day regimen of 1.5 L
PEG-ASC + 5 mL PICO the day prior in terms of the efficacy of bowel preparation for afternoon

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Masahiro Tajika et alcolonoscopy. However, the same-day regimen was preferred by patients. The 2-L PEG-ASC
split-dose regimen is feasible for Japanese patients and may be an option for patients with poor
defecation who required additional preparation on previous examinations or patients who had
vomited during previous preparations.

ACKNOWLEDGMENTS
The authors would like to thank Ms. Noriko Yasui for her significant assistance with patientconsent and data collection, and Ms. Maki Ito and Ms. Fumiko Sugiura for research assistanceand for creating the study database. The authors would also like to acknowledge all nursing
staff on the ward and in the endoscopy unit for providing assistance.

CONFLICTS OF INTEREST
Masahiro Tajika received honoraria from EA Pharma Co., Ltd.
All other authors have no conflicts of interest to declare for this work.

AUTHOR CONTRIBUTIONS
MT contributed to study concept and design, data collection, and writing of the draft
manuscript; TT, MI, YH, SO, NM, TK, NO, SM, KT, MO, YK, and SK contributed to study
design and data collection; MA contributed to analysis and interpretation of data. VB, HK, andYN contributed to study design and revised the manuscript. All authors read and approved thefinal manuscript.

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