THE TRIANGULAR TEST TO ASSESS THE EFFICACY OF METOCLOPRAMIDE IN GASTROESOPHAGEAL REFLUX

Background: Sequential methods are particularly interesting when recru itment is difficult because they may allow a study to be stopped early while maintaining type I and II error rates. Methods: This placebo-co ntrolled, randomized double-blind study was aimed at assessing the eff icacy of metoclopramide (0.2 mg/kg three times daily during 14 days) o n gastroesophageal reflux in infancy. The main end point was the relat ive variation of the percentage of time at pH <4 between inclusion (da y 0) and evaluation (day 14) assessed on two 24-hour esophageal pH rec ordings. Statistical analysis was performed with use of a sequential m ethod, the triangular test. Results: The study was stopped after the s eventh analysis (39 infants evaluated: 20 placebo and 19 metoclopramid e) without showing the expected benefit. Improvement on the main end p oint was 30% +/- 48% (mean +/- SD). Corresponding unbiased median esti mates were 22% for placebo and 39% for metoclopramide (p = 0.28, seque ntial analysis). On day 14, the percentage of time at pH <4 was 8.1% /- 11.7% for placebo and 6.7% +/- 9.2% for metoclopramide (p = 0.68, t test), and the number of reflux episodes >5 minutes was 3.0 +/- 3.5 f or placebo and 1.9 +/- 3.0 for metoclopramide (p = 0.33, t test). Conc lusion: If a tendency for a superior improvement with metoclopramide t han with placebo was observed on the main end point, it was lower than expected and the difference was not significant. Compared with the co rresponding single-stage design, the triangular test allowed to stop t he study with a 15% reduction in sample size.