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The triangular test to assess the efficacy of metoclopramide in gastroesophageal reflux
Author(s) -
Bellissant Eric,
Duhamel JeanFrançois,
Guillot Marcel,
ParienteKhayat Ann,
Olive George,
Pons Gerard
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90170-3
Subject(s) - metoclopramide , placebo , reflux , medicine , anesthesia , antiemetic , confidence interval , vomiting , alternative medicine , disease , pathology
Background Sequential methods are particularly interesting when recruitment is difficult because they may allow a study to be stopped early while maintaining type I and II error rates. Methods This placebo‐controlled, randomized double‐blind study was aimed at assessing the efficacy of metoclopramide (0.2 mg/kg three times daily during 14 days) on gastroesophageal reflux in infancy. The main end point was the relative variation of the percentage of time at pH <4 between inclusion (day 0) and evaluation (day 14) assessed on two 24‐hour esophageal pH recordings. Statistical analysis was performed with use of a sequential method, the triangular test. Results The study was stopped after the seventh analysis (39 infants evaluated: 20 placebo and 19 metoclopramide) without showing the expected benefit. Improvement on the main end point was 30% ± 48% (mean ± SD). Corresponding unbiased median estimates were 22% for placebo and 39% for metoclopramide ( p = 0.28, sequential 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 for placebo and 1.9 ± 3.0 for metoclopramide ( p = 0.33, t test). Conclusion If a tendency for a superior improvement with metoclopramide than with placebo was observed on the main end point, it was lower than expected and the difference was not significant. Compared with the corresponding single‐stage design, the triangular test allowed to stop the study with a 15% reduction in sample size. Clinical Pharmacology & Therapeutics (1997) 61 , 377–384; doi: