Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study

Background: Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to ma ke cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc a nd other ventricular arrhythmias occurred while the drug was used concomita ntly with contraindicated drugs. This study sought to analyze electrocardio grams (ECGs) from a multicenter pediatric study and to identify abnormaliti es in QTc interval associated with cisapride use. Methods: Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical t herapy 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 bas eline values after 3 to 8 weeks of treatment. Results: Mean QTc among patients taking the drug was 408 +/- 18 ms. None wa s higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2 +/- 20 ms. Conclusions: In our study group of children without underlying cardiac dise ase or electrolyte imbalance, cisapride was found to have no significant ef fect on cardiac electrical function compared with placebo. These results ar e consistent with the drug's record of exceedingly infrequent cardiac event s. Because the availability of this prokinetic is threatened, its safety an d the safety and efficacy of alternative treatment options (including surge ry) should be studied further.