Cisapride treatment for gastro-oesophageal reflux in children.

BACKGROUND

Gastro-oesophageal reflux (GOR) is common and usually self-limiting in infants. Cisapride, a pro-kinetic agent, was commonly prescribed until reports of possible serious adverse events were associated with its use.

OBJECTIVE

To determine the effectiveness of cisapride versus placebo or non-surgical treatments for symptoms of GOR.

METHODS

We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialised Register and Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, reference lists of relevant review articles and searched in the Science Citation Index for all the trials identified. All searches were updated in February 2009.

METHODS

Randomised controlled trials comparing oral cisapride therapy with placebo or other non-surgical treatments for children diagnosed with GOR were included. We excluded trials with a majority of participants less than 28 days of age.

METHODS

Primary outcomes were a change in symptoms at the end of treatment, presence of adverse events, occurrence of clinical complications and weight gain. Secondary outcomes included physiological measures of GOR or histological evidence of oesophagitis. We dichotomised symptoms into 'same or worse' versus 'improved' and calculated summary odds ratios (OR). Continuous measures of GOR (for example reflux index) were summarised as a weighted mean difference. All outcomes were analysed using a random-effects method.

RESULTS

Ten trials in total met the inclusion criteria. Nine trials compared cisapride with placebo or no treatment, of which eight (262 participants) reported data on symptoms of gastro-oesophageal reflux. There was no statistically significant difference between the two interventions (OR 0.34; 95% CI 0.10 to 1.19) for 'same or worse' versus 'improved symptoms' at the end of treatment. There was significant heterogeneity between the studies, suggesting publication bias. Four studies reported adverse events (mainly diarrhoea); this difference was not statistically significant (OR 1.80; 95% CI 0.87 to 3.70). Another trial found no difference in the electrocardiographic QTc interval after three to eight weeks of treatment. Cisapride significantly reduced the reflux index (weighted mean difference -6.49; 95% CI -10.13 to -2.85; P = 0.0005). Other measures of oesophageal pH monitoring did not reach significance. One included study compared cisapride with Gaviscon (with no statistically significant difference). One small study found no evidence of benefit on frequency of regurgitation or weight gain after treatment with cisapride versus no treatment, carob bean or corn syrup thickeners.

CONCLUSIONS

We found no clear evidence that cisapride reduces symptoms of GOR. Due to reports of fatal cardiac arrhythmias or sudden death, from July 2000 in the USA and Europe cisapride was restricted to a limited access programme supervised by a paediatric gastrologist.