Colon Preparation With 2L PEG in Combination With Lubiprostone vs 4L PEG
Condition: Indication for Modification of Patient Status (Diagnosis)
Study type: Interventional
Phase: Phase 4

Summary: 
      Colonoscopy is the current standard method for examination of the colon. Bowel cleansing
      prior to colonoscopy is the essential prerequisite to ensure complete mucosal visualization
      and lesion identification.(1,2) Suboptimal preparations are associated with missed diagnoses,
      longer procedure times and increased costs related to the repeat procedures and shortened
      intervals between procedures.(3-5) Inadequate preparations have been noted in around 25 %
      cases in the US.(4,6) This has been attributed primarily to poor patient tolerance to the
      standard colon preparations.

      Osmotically balanced polyethylene glycol (PEG) electrolyte bowel lavage solutions were
      introduced in 1980.(7) These PEG based solutions are the most commonly used bowel
      preparations today.(7) They have high efficacy, are safe and are associated with minimal
      fluid and electrolyte imbalance. However the major drawback of these preparations is the
      taste and the large volumes required with associated nausea, cramping and vomiting.(8) This
      often results in poor compliance and tolerance with resultant poor preparation and improper
      visualization. A pooled analysis of 15 trials found that at least 29 % of patients were
      unable to complete their PEG solution.(9) Lubiprostone (LB) is a locally acting selective
      Type 2 chloride channel activator which causes intestinal fluid secretion. This results in
      increased softened stool and increased intestinal transit without the loss of either net
      intravascular fluid or electrolytes.(10) Peak plasma levels occur approximately 1.14 h after
      oral administration of a single 24 microgram dose, and the half-life of lubiprostone (t½) has
      been estimated at approximately 3 h.(11,12) LB is currently approved for the treatment of
      chronic idiopathic constipation and is generally well tolerated with an excellent side effect
      profile. Even long term usage has not shown clinically significant changes in electrolyte
      levels.(10,13) Our hypothesis was that administration of LB in addition to low volume (2-L)
      split-dose PEG would improve the adequacy of the bowel preparation as comparable as standard
      4-L split-dose PEG regimens. Additionally, it could improve patient tolerability and
      decreased side effects related to the large volume of PEG regimens. Accordingly, we conducted
      this prospective, single-blind, randomized controlled trial.
    

Detailed description: 
      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).
    

Intervention name(s): polyethylene glycol in combination with lubiprostone; polyethylene glycol alone
Intervention type(s): Drug; Drug
Intervention description(s): 2-litre polyethylene glycol split-dose in combination with one 24 mcg tablet of lubiprostone; 4-litre polyethylene glycol split-dose
Other intervention name(s): NIFLEC in combination with Amitiza; NIFLEC alone
Intervention MeSH terms: Lubiprostone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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 patients to their group and instructed them on the proper use of their assigned bowel preparation method as well as dietary advice.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: colonoscopy; polyethylene glycols; lubiprostone