Tolerability, Efficacy and Mucosal Inflammation Associated With Orally Administered Colon Cleansing for Colonoscopy
Condition: Colonoscopy
MeSH terms: Mucositis; Inflammation
Study type: Interventional
Phase: Phase 4

Summary: 
      Colonoscopy is the gold standard investigation for assessing the lining of the colon. Colon
      cleansing preparations are required to be taken prior to colonoscopy to provide effective
      visualisation and identification of any abnormalities and different types of colon cleansing
      preparations exist.

      Some colon cleansing preparations have been shown to cause visible changes in the lining of
      the bowel which may cause confusion and incorrect diagnoses to be made.

      This audit aims to assess the ability of different colon cleansing preparations to clear the
      colon of faeces. The tolerability of each will also be assessed, as will any changes in the
      lining of the bowel to assess if one type of colon preparation is more likely to cause
      visible changes than another.
    

Detailed description: 
      There are several published trials of different colon cleansing agents for colonoscopy (which
      is the investigation of choice for visualisation of the colonic mucosa) which compare
      different regimens. However, a recent published meta-analysis has shown that most audits and
      studies were underpowered with poor study design and so no consensus on the most effective
      preparation exists1. 10-20% of failed colonoscopy is attributable to inadequate bowel
      cleansing which has a negative impact on the detection of potential malignant lesions in the
      colon3 as well as requiring the patient to attend again for further colonoscopy after
      repeated colon cleansing which also impacts on waiting lists and healthcare costs.

      Colon cleansing preparations can be broadly classified into three groups. Osmotic laxatives
      such as sodium phosphate (NaP) increase colon water content by attracting extracellular fluid
      efflux through the bowel wall. Polyethylene glycol (PEG) laxatives are high molecular weight
      non-absorbable polymers that are administered in a dilute electrolyte solution, this is
      retained in the colon where it acts as a bowel cleanser without any significant fluid
      exchange across the colonic mucosa. The third group are stimulant laxatives such as senna or
      sodium picosulphate which work primarily by enhancing smooth muscle contractility and also
      they may increase bowel water content.

      Previous published audits and studies comparing different types of colon cleansing
      preparations have been limited by small sample size with only 5 published papers having over
      100 patients in each arm of the study. These 5 studies suggest that NaP may be better than
      PEG but the recent meta-analysis failed to show this, primarily due to the large number of
      smaller studies showing PEG was better than NaP. Interpretation of the studies is limited by
      inconsistent and poorly defined measures of efficacy outcome. Most studies have used a
      subjective endoscopists assessment of the overall quality of the bowel preparation making
      comparisons between studies impossible. Recently a calibrated externally validated outcome
      assessment tool has been developed to objectively quantify the quality of bowel preparation4,
      but no randomised published study has yet utilised this tool.

      In the absence of clear difference in efficacy between preparations then patient tolerability
      is likely to be an important distinguishing feature when selecting a treatment. Data on
      tolerability outcomes is limited but there is some evidence that PEG solutions are less well
      tolerated due to the volume of liquid required to drink. This is an area where further study
      is needed.

      The ability of a colonic cleansing preparation to clean the colon effectively also must be
      balanced by its ability to not induce changes in the lining of the bowel itself. Ulceration
      and inflammation of the colon has been shown to occur in 3-24% of patients using NaP compared
      with 1-2% in those receiving PEG. Such findings can be mistaken for inflammatory bowel
      disease such as Crohns or put down to drug induced changes such as non steroidal anti
      inflammatory agents (NSAIDs). However, these studies have been either non randomised5 or
      underpowered to detect real differences.

      The most satisfactory colonic cleansing agent in terms of efficacy, tolerability and safety
      therefore remains unclear.

      The aims of the project are:

        1. To assess which bowel preparation provides the best colon cleansing using a validated
           score.

        2. To assess the incidence of mucosal inflammation/ulceration induced by each colon
           cleansing agent.

        3. To see which colon cleansing agent is best tolerated by patients.

      The information gained from this audit will enable the type of colonic cleansing preparation
      to be tailored to the subjects indication for requiring colonoscopy. For example in those
      with possible inflammatory bowel disease the colon cleansing agent which produces the least
      mucosal inflammation would be required to reduce the incidence of a false positive diagnosis
      whilst the colon cleansing agent which is most tolerable may be more important in the
      elderly.

      This study will be a prospective blinded audit comparing three colon cleansing agents, which
      are used routinely in clinical practice for colonoscopy. The three will be Sodium Phosphate
      (Fleet), Sodium Picosulphate (Picolax/Picoprep) and PEG (Colonlytlye).

      All patients who are referred to undergo colonoscopy would be entered into the study except
      for:

        1. Prior history of inflammatory bowel disease or suspected inflammatory bowel disease, or
           patients on current non steroidal antiinflammatory medication (excluding low dose
           aspirin). These patients may have mucosal inflammation/ulceration which would prevent
           analysis of mucosal abnormalities due to the colon cleansing agent and so would not be
           studied.

        2. Patients with heart failure (NYHA >2) or renal failure (GFR<30) (since fluid shifts
           associated with sodium phosphate bowel preparation have been reported).

        3. All patients over the age of 75 due to potential dehydration and hyperphosphatemia from
           the bowel preparations.

      Each patient would be randomised to receive one of the three colon cleansing agents (Sodium
      Phosphate, Sodium Picosulphate or PEG) that are routinely used in clinical practice. The
      endoscopy administration staff at each site would be responsible for random allocation of the
      bowel preparation using random number generation with the resultant bowel preparation being
      collected by the patient from a pharmacy, as per usual practice, prior to the colonoscopy.
      There are no exclusion criteria for bowel preparation selection.

      On the day of colonoscopy but prior to the procedure an assessment of the tolerability of the
      colon cleansing agent would be made using a questionnaire.

      During colonoscopy an assessment of the efficacy of the colon cleansing agent is made by the
      blinded colonoscopist using the previously validated Ottawa bowel preparation assessment
      tool.
    

Intervention name(s): Colonlytely; Picolax/Picoprep; Fleet
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Bowel preparation; Bowel preparation; Bowel preparation
Other intervention name(s): Polyethylene glycol; Picosulphate; Sodium Phosphate
Intervention MeSH terms: Picosulfate sodium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Mucosal inflammation; Fleet; Picoprep; Colonlytely; Colonoscopy; tolerability; efficacy