Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study. Cisapride 20 mg b.i.d. provides symptomatic relief of heartburn and related symptoms of chronic mild to moderate gastroesophageal reflux disease. CIS-USA-52 Investigator Group. Effect of cisapride on excessive regurgitation in infants. Cisapride in the control of symptoms in infants with gastroesophageal reflux: A randomized, double-blind, placebo-controlled trial. Cisapride treatment of constipation-predominant irritable bowel syndrome is not superior to placebo. Cisapride in pediatric gastroesophageal reflux. The symptomatic effect of cisapride in patients with irritable bowel syndrome and constipation.
Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use.
                Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment.
                Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms.
                In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further. We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis.
                After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk.
                Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group.
                Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD. The relevance of the upper gastrointestinal motility-stimulating effects of cisapride for the treatment of excessive regurgitation and vomiting in infants was studied in 137 patients aged less than 1 year. They were treated with placebo or with cisapride, 0.1 to 0.2 mg/kg three times daily, for up to four weeks. In a dose-dependent fashion, cisapride significantly reduced the frequency and severity of regurgitation: after four weeks of treatment at 0.15 to 0.2 mg/kg, only about 20% of infants still had moderate or severe regurgitation, compared with about two thirds of those treated with placebo. Although only a few patients were followed up, the duration of treatment (four weeks) appeared to be long enough to minimize relapse. Side effects were limited to phenomena indicative of stimulated bowel motility. To evaluate the efficacy of cisapride in the treatment of uncomplicated gastroesophageal reflux in children younger than 36 months of age.
                A total of 95 patients satisfied the entry criteria and were randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2 mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week treatment period, symptom diary and parental evaluation with repeat 24-hour pH study were performed.
                Sixty-eight patients completed the trial (38 in the cisapride group and 30 in the placebo group). There were no significant differences in the symptoms of crying, vomiting, or gagging; the overall symptom intensity score; or parental global evaluations. There was a significant difference (P <.03) in the percent time pH <4, the number of reflux episodes lasting more than 5 minutes, and the duration of the longest episode. No significant difference was demonstrated for the number of episodes with pH <4 or the reflux score.
                Cisapride was no better than placebo for relief of symptoms in children with uncomplicated gastroesophageal reflux. A beneficial effect was demonstrated in the cisapride group in relation to the measured parameters for esophageal acid exposure time. Previous studies with cisapride reported conflicting results in patients with constipation-predominant irritable bowel syndrome (IBS). To gain further evidence, this randomized double-blind study was carried out.
                Eighty-two symptomatic outpatients were randomized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks. In patients without satisfactory improvement after 4 weeks, the dose was doubled. Symptom evaluation used visual analog scales (VAS) and the investigators' global assessment.
                After 4 weeks, in 18 (45%) cisapride and 24 (57%) placebo patients the dose was doubled because of insufficient improvement of symptoms. The mean VAS score for patients' global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo, and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment. Investigators rated the overall effect of therapy as good or excellent in 70% of the cisapride and 50% of the placebo group. Neither these nor further efficacy parameter differences reached statistical significance.
                These results indicate that the effect of 15-30 mg cisapride daily on symptoms of constipation-predominant IBS is not significantly superior to placebo. During the 12 week treatment of this trial cisapride proved to be safe and tolerable. Gastroesophageal reflux is a common condition that in infants may lead to serious complication. This study assessed the efficacy and safety of oral cisapride suspension in the treatment of children 6 weeks to 2 years old with daily regurgitant reflux.
                A randomized, prospective, double-blind, placebo-controlled clinical trial was conducted at three study sites. After a 1 week baseline assessment, 45 infants 6 weeks to 2 years old were randomized to a double-blind trial in which they received a 6 week course of cisapride (0.2 mg/kg q6h) or a placebo suspension. Efficacy was assessed with 24 hour esophageal pH monitoring, esophageal manometry, and esophageal biopsy before and after the treatment period. A diary of regurgitation frequency and severity was kept by the parents. Safety was assessed by adverse event monitoring and standard laboratory measurements.
                Compared with placebo, cisapride significantly (p < 0.05) reduced the mean duration of upright and supine reflux episodes. Compared to baseline, cisapride significantly reduced the mean duration of the longest reflux episode, and placebo increased the mean number of reflux episodes longer than 5 minutes. Cisapride was not significantly different from placebo for the following mean measurements: percent of total time pH < 4, number of reflux episodes, lower esophageal sphincter pressure, swallow pressure, regurgitation frequency or global evaluation scores.
                Cisapride is a safe, well tolerated prokinetic agent that improves the esophageal clearance of refluxed gastric acid in children under the age of 2 years. Cisapride improves symptoms in patients with idiopathic constipation. This trial compares the effect of cisapride with that of placebo in patients with irritable bowel syndrome (IBS) and constipation.
                Seventy patients were randomized to 12 weeks' treatment with 5 mg cisapride three times daily or placebo in a double-blind trial. The dose could be doubled after 4 weeks in patients without satisfactory improvement. The patients scored their symptoms on a 100-mm visual analogue scale (VAS) (0 = best, 100 = worst), and the investigators evaluated the symptomatic effect.
                The dose was doubled in 17 and 23 patients in the cisapride and placebo groups, respectively, after 4 weeks. The patients' mean VAS score for global evaluation of IBS symptoms in the cisapride and placebo groups was 73 and 71 mm, respectively, at the start of treatment and 47 and 41 mm at the end. The difference between cisapride and placebo at the end was 6 mm in favour of placebo (95% confidence interval (CI), -6, 18) (NS). The investigators evaluated the effect as good or excellent in 39.2% and 58.8% in the cisapride and placebo groups, respectively. The difference in favour of placebo was 19.5% (95% CI, -5, 44) (NS). Nor were any statistically significant differences seen between cisapride and placebo in the other effect factors.
                The trial seems to exclude a clinically significant effect of 15-30 mg cisapride daily in patients with IBS and constipation during a 12-week treatment period.
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.