Gastric motility abnormalities in pediatric gastroesophageal reflux disease: A comprehensive review of mechanisms and therapeutic implications

Table 3 Clinical trials assessing the efficacy of domperidone in the treatment of gastroesophageal reflux disease in children

Ref.	Participants, n (age range)	Cases/controls	Design	Outcome	Comments on the study
De Loore et al[111], 1979	47 (3 weeks to 8 years)	Children with regurgitation/vomiting	Blinded RCT with placebo-controlled arm; domperidone vs metoclopramide vs placebo	Domperidone was superior to a placebo. Domperidone proved to be superior in reducing symptoms compared to metoclopramide	Assessment of symptoms of younger children, especially regurgitation, may have been problematic
Carroccio, et al[112], 1994	80 (1-18 months)	GERD with no erosion. All children were assessed with upper GI endoscopy and pH study	Blinded RCT: Group 1: Domperidone with magnesium hydroxide + aluminium hydroxide; Group 2: Domperidone with alginate; Group 3: Domperidone; Group 4: Placebo, duration 8 weeks	Group 1 showed significant improvement of symptoms and reflux index compared to Groups 2 and 3 (P < 0.018 and P < 0.034 respectively). The domperidone group reported fewer reflux episodes (59 vs 48.5, P < 0.009) and improvement in clinical score before and after treatment (P < 0.04)	A well-conducted study with real-life use of domperidone combined with antacids or alginates. The control group was also appropriate. Assessment was done with pH
Bines et al[113], 1992	17 (5 months to 12 years)	GERD is unresponsive to non-pharmacological treatments and confirmed with pH studies	Blinded RCT with domperidone and placebo arms for 8 weeks	No significant difference in symptom improvement. Only 25% reduction in postprandial reflux episodes in children on domperidone	A small number of patients; age range varies widely, and it could be difficult to assess symptoms in younger children; randomization was not clear; some patients had other diseases
Grill et al[114], 1985	15 (3-13 months)	Babies with symptoms of GERD, like vomiting, spitting, coughing, irritability, and choking, after 2 weeks of non-pharmacological interventions	Open-label study with domperidone for 6 weeks	Improvement of the mean symptom score at 3 weeks and 6 weeks. Reduction of post-prandial reflux time and peristaltic esophageal contractions	The study's open-label design makes it difficult to interpret the results
Hegar et al[115], 2009	20 (2-9 months)	Symptomatic GERD not responding to conservative interventions	Randomized, investigator-blind, open label trial domperidone vs cisapride for 4 weeks	Both drugs were equally effective in reducing the daily frequency of regurgitation, reducing the trends of reflux index, and the number of refluxes/24 hours. No statistical difference between drugs	The open-label nature of the prescription makes it difficult to interpret results. However, the authors have randomized the population, and the investigators are blinded
Cresi et al[116], 2008	26 term and preterm neonates	Symptomatic GERD not responding to non-pharmacological interventions	Open-label, randomized, placebo-controlled trial. Domperidone was given at 8 hours and 16 hours during a 24-hour pH recording with a meal	Increase in reflux frequency and reduction in reflux duration in the group receiving domperidone	The open-label nature of the study makes it difficult to interpret the results. Assessment of symptoms in preterm babies could have been misinterpreted

GERD: Gastroesophageal reflux disease; RCT: Randomized controlled trial; GI: Gastrointestinal.