Colon Preparation With 2L PEG in Combination With Lubiprostone vs 4L PEG

Study design:

This was a single center prospective, single-blind, randomized controlled trial to compare the quality of bowel preparation using 2-L PEG with LB vs. 4-L PEG conducted from September 2019 to June 2020 at Department of Medicine, Rajavithi Hospital, a tertiary referral center in Bangkok, Thailand. It was performed in accordance with the clinical principles laid down in the Declaration of Helsinki and informed consent was obtained from all the participants before their enrollment. The study protocol was reviewed and approved by the ethics committee of Rajavithi Hospital. Recruitment, enrollment, randomization, withdrawal, and completion were done according to the consort guidelines.

Bowel preparation method:

PEG used in the present study was Niflec® (Meiji, Japan), which composed of macrogol 4,000 plus electrolytes (sodium sulfate, sodium hydrogen carbonate, sodium chloride, and potassium chloride) and is taken by diluting one sachet into 2-L of plain water. The participants were instructed to take 250 mL every 15 min untill the entire solution was consumed. In cases of 4-L split-dosage, half dose preparation started in the evening of the pre-procedure day at about 8.00 to 10.00 pm and the remaining dose was given in the morning at about 5.00 to 7.00 am on the procedure day. In cases of 2-L split-dosage, half dose preparation started in the evening of the pre-procedure day at about 8.00 to 9.00 pm and the remaining dose was given in the morning at about 5.00 to 6.00 am on the procedure day. And these patients, one 24 mcg tablet of LB was given 2 hours before PEG ingestion (at 6.00 pm of the pre-procedure day).

Dietary advice was given to all patients. Consumption of fruit, legumes, or vegetable was forbidden 2 days before the procedure. On the day before colonoscopy patients had a light breakfast and lunch, but a liquid dinner (clear soup). Solid food was not allowed at the start of the bowel preparation phase. All patients were instructed to fast from midnight before procedure day, but some anti-hypertensive drugs and minimal plain water were permitted.

Randomization:

All participants attended an informational session before colonoscopy where the participants were counseled about the nature of the study and written informed consent was obtained. The research coordinator used a computer to generate a randomization table with blocks of 8. Allocation concealment was maintained through the use of consecutively numbered sealed envelopes. The allocation ratio was 1:1 in 2-L PEG with LB (Group A) or 4-L PEG (Group B).

An endoscopy nurse assigned the participants to their group and instructed the participants on the proper use of their assigned bowel preparation method as well as dietary advice. Gastroenterologists and investigators were blinded to the allocation groups. The participants were given a questionnaire measured the tolerability and side effects of the bowel preparation regimen, to be completed once their bowel preparation was finished and before coming to the hospital for the colonoscopy.

Colonoscopy:

All colonoscopies were performed by 3 experienced gastroenterologists (minimum experience of 1000 procedures; Apichet Sirinawasatien, Kanokpoj Chanpiwat, and Tanyaporn Chantarojanasiri) at the Rajavithi Hospital. A standard protocol for insertion, withdrawal, and observation was followed. All colonoscopies were performed using video colonoscopes (CF 180, Olympus, Japan) under moderate sedation.

The colon segment including the rectum and extending up to the splenic flexure was termed as left colon; the segment between splenic flexure and hepatic flexure was termed transverse colon; while colon segment proximal to hepatic flexure, including the cecum was termed right colon for the purpose of this study. A complete colonoscopy was defined as reaching the cecum determined by the visualization and documentation of the ileocecal valve and appendiceal orifice. Failed colonoscopy was defined as endoscope could not reach ileocecal valve and cecum. Overall procedure times was the times between the endoscope enter and withdraw from the anus.

During the insertion of the scope, two representative pictures were taken from each of these three segments to document the colon preparation. An early colonoscopy was defined as a procedure initiated during 8-11 am while those started after 11 am were considered the late procedure.

Colon cleansing scale:

The investigators used Boston bowel preparation scale (BBPS) score to evaluate the adequacy of the preparation. Each colonic segment was graded from 0 (solid stools) to 3 (no residual staining). The aggregate score was obtained by adding the score for all 3 segments, thus resulting in a score between 0 and 9. A score ≤4 was considered a poor colon preparation, resulting in a recommendation for a repeat procedure. A score of 8-9 was considered excellent preparation while a score of 5-7 was considered adequate preparation.

The colon preparation was graded by analyzing photo documentation obtained during a colonoscopy by three gastroenterologists (AS, KC, and TC) after the procedure finished. The mean BBPS score of each patient was calculated and recorded the result on a separate standardized form.

Sample size calculation and statistical analysis:

Descriptive statistics were used for baseline characteristics. The Boston bowel preparation scale produces data that are approximately normally distributed. Two-group ANOVA was used to assess for the presence of group differences in the preparation scores while accounting for procedure time (early versus late). The proportion of adequate bowel preparation in each group was compared with a chi-square statistic. The secondary endpoints of tolerability and side effects were assessed using the Mann-Whitney U test.

The sample size was calculated using two independent means formula (two-tailed test) based on data from a previous study in 2008,(16) in which the patient mean overall symptom questionnaire ratings of the PEG plus LB group was 3.7±1 compared to 3.2±1.1 in the controlled group (p = 0.003). The minimum required number of participants was calculated at 70 in each group in order to detect a significant association with 80% power (β =0.20) and a 5% probability of type I error (2-sided) (α =0.05).