Research Article: Randomised clinical trial: the efficacy of prucalopride in patients with chronic intestinal pseudo-obstruction – a double-blind, placebo-controlled, cross-over, multiple n = 1 study

Date Published: January 08, 2012

Publisher: Blackwell Publishing Ltd

Author(s): A V Emmanuel, M A Kamm, A J Roy, R Kerstens, L Vandeplassche.

http://doi.org/10.1111/j.1365-2036.2011.04907.x

Abstract

Chronic intestinal pseudo-obstruction is a disabling condition for which there are no established drug therapies. The condition is caused by a diverse range of intestinal myopathies and neuropathies.

To assess the therapeutic efficacy of prucalopride, a selective high-affinity 5-HT4 receptor agonist, we employed a multiple n = 1 study design. Each patient acted as his/her own control, each day counting as one treatment episode, allowing comparison of 168 days on each of active drug and placebo.

Double-blind, randomised, placebo-controlled, cross-over trial of four 12-week treatment periods, with 2–4 mg prucalopride or placebo daily. In each of the first and second 6 months there was a prucalopride and a placebo treatment. Patients with proven chronic intestinal pseudo-obstruction, including dilated gut, were included. Evaluation was by patient diary and global evaluation.

Seven patients participated (mean 42 years, five female, median symptom duration 11 years). Three discontinued, two due to study length, and one on prucalopride due to unrelated malnutrition and bronchopneumonia. Four patients (three visceral myopathy and one visceral neuropathy) completed the study; prucalopride significantly improved pain in three of four patients, nausea in two, vomiting in one, bloating in four and analgesic intake. Bowel function was not changed substantially.

n = 1 studies in rare conditions allow drug efficacy assessment. Prucalopride relieves symptoms in selected patients with chronic pseudo-obstruction.

Partial Text

The term chronic idiopathic intestinal pseudo-obstruction (CIP) denotes a clinical syndrome of apparent bowel obstruction in the absence of an obstructing lesion. The term ‘pseudo-obstruction’ was first used to describe a cohort of patients with recurrent vomiting, abdominal pain and distension, who had undergone repeated laparotomy with no obstructive cause demonstrated.1 The symptoms relate in part to the failure of intestinal propulsion, due to an underlying disorder of enteric nerves or muscle.

Patients recorded the following data on a daily basis in their diary:

A large number of studies have demonstrated previously that prucalopride is effective in relieving symptoms in patients with chronic constipation.11–15 In particular, prucalopride increases bowel frequency and reduces abdominal bloating and pain.11 This study has shown that in some patients with chronic intestinal pseudo-obstruction prucalopride is effective in alleviating symptoms. To our knowledge this is the first long-term, double-blind, placebo-controlled, randomised study to show therapeutic benefit from medication in this disabling condition. Specifically, it was most effective in relieving the symptom of bloating. There are few, if any, options for managing this symptom.16 Prucalopride was also shown to be effective in reducing abdominal pain and nausea. Prucalopride reduced the frequency and severity of these symptoms.

 

Source:

http://doi.org/10.1111/j.1365-2036.2011.04907.x

 

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