Cisapride treatment of constipation-predominant irritable bowel syndrome is not superior to placebo. The symptomatic effect of cisapride in patients with irritable bowel syndrome and constipation. Effect of cisapride on chronic idiopathic constipation in children. "Prokinetic" treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride. Cisapride for the treatment of constipation in children: A double-blind study. Cisapride in management of chronic pediatric constipation. Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study. Effect of cisapride on excessive regurgitation in infants. 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.
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. 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. The efficacy of cisapride, a new prokinetic drug, as a treatment for chronic functional constipation of childhood was studied in 20 constipated children. Each subject had a stool frequency less than 4/week and/or total gastrointestinal transit time greater than 33 hr and was randomly assigned to double-blind treatment with either cisapride (N = 10) or placebo (N = 10) for 12 weeks. Stool habits, total gastrointestinal transit time, and anorectal motility were evaluated in all children before and at the end of the treatment period. Cisapride significantly increased stool frequency from 1.2 +/- 0.6 to 5.1 +/- 1.9 stools/week (mean +/- SD; P less than 0.05), whereas the lesser effect of placebo was not significant (1.2 +/- 0.8 to 2.8 +/- 0.8 stools/week; P = 0.4). Both treatments significantly (P less than 0.05) decreased laxative or suppository use. Total gastrointestinal transit time was decreased by cisapride (90.8 +/- 9.2 hr to 57.2 +/- 20.2 hr; P less than 0.05) but was not affected by placebo. Anorectal manometry showed that cisapride, but not placebo, significantly decreased the rectoanal inhibitory reflex threshold and the conscious rectal sensitivity threshold. It is concluded that cisapride improves gastrointestinal motility and bowel habits in children with chronic idiopathic constipation and may be useful in the management of some children with this disorder. The effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome (IBS) were evaluated in a randomized, double-blind, placebo-controlled study. Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d.; this dosage could be changed if necessary. The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 (p less than 0.05) during weeks 8-12 of treatment, and the number of days with stools of normal consistency increased to 3.5 and 1.9 (p less than 0.05), respectively. At week 12, the reduction in severity and frequency scores for abdominal pain was significantly greater (p less than or equal to 0.05) in the cisapride group (60 and 61%) than in the placebo group (40 and 32%), as it was for abdominal distension (p less than 0.05). Cisapride tended to be better than placebo in diminishing flatulence. In 71% versus 39% of the patients the overall rating for the response to treatment was good or excellent at week 12. Cisapride was well tolerated. These results suggest that the drug will be useful for the management of constipation-predominant IBS. To determine whether cisapride is effective in the treatment of children with constipation.
                Double-blind, placebo-controlled study in which children with chronic constipation were randomly assigned to treatment with cisapride or placebo for 12 weeks.
                Forty children were enrolled, and 36 completed the therapy. Treatment successes occurred in 13 of 17 (76%) subjects in the cisapride group and 8 of 19 (37%) subjects in the placebo group (P <.03). The odds ratio for response after cisapride administration was 8.2 times higher (95% CI 1.3 to 49.4). During cisapride therapy, there was a significant improvement in number of spontaneous bowel movements per week (from 0.9 +/- 0.1 to 4.1 +/- 1.1), and there was a significant decrease in number of fecal soiling episodes per day (1.8 +/- 0.5 to 0.08 +/- 0.4), percent with encopresis (82% vs 23%), number of laxative doses per week (from 10.3 +/- 2.6 to 0.8 +/- 0.6), percent using laxatives (77% to 24%), and total gastrointestinal transit time (from 115.0 +/- 3.7 hours to 77.0 +/- 11.1 hours). With placebo, there were no significant changes in the number of spontaneous bowel movements (from 1.0 +/- 0.8 to 2.2 +/- 0.6), percent with encopresis (74% vs 47%), or total gastrointestinal transit time (from 112.5 +/- 4.9 hours to 95.4 +/- 9.8 hours); but there was a significant decrease in number of fecal soiling episodes per day (from 1.3 +/- 0.4 to 0.4 +/- 0.2) and number of laxative doses used per week (from 11.5 +/- 2.9 to 2.05 +/- 0.7). The final number of spontaneous bowel movements, fecal soiling episodes, laxatives used, or percent patients with encopresis was not different when patients receiving cisapride were compared with those receiving placebo.
                Cisapride was effective in the treatment of children with constipation. This study was conducted to explore the use of cisapride in the treatment of chronic idiopathic constipation in children.
                Seventy-nine children were screened. Seventy-three of them met the selection criteria that included clinical, laboratory, radiologic, and histopathologic investigations. These patients entered a week-long phase I of disimpaction using lactulose. Four of them were noncompliant and thus were excluded from the next phase. In phase II sixty-nine patients were assigned to two treatment groups: 0.3 mg/kg cisapride four times a day versus matching placebo for 8 weeks in a double-blind study. The two groups that completed phase II were similar in age and duration of symptoms, confirmed by statistical analysis. Stool frequency was assessed weekly, beginning at the end of the disimpaction phase and continuing for 9 weeks. Total gastrointestinal transit time was measured twice, on completion of phase I and 9 weeks later. Transit time is the time required for a carmine marker taken orally after overnight fast to appear in the stool.
                There was a significant difference between stool frequency per week before and after cisapride treatment, stool frequency per week at the end of phase II with cisapride versus placebo, and total gastrointestinal transit time before and after treatment with cisapride (p < 0.05 for all values). No such difference was demonstrated when comparing stool frequency per week or total gastrointestinal transit time before and after placebo (p > 0.05 for both).
                Cisapride may have a role in the management of chronic idiopathic constipation in children. 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. 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. 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.
No clear benefit can be demonstrated with cisapride. We do not feel that cisapride can be justifiably used for chronic constipation or irritable bowel disease given its side effects of arrhythmia and associated 175 recorded deaths.