title: Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease.
abstract: OBJECTIVE
  The typical symptoms of gastroesophageal reflux disease (GERD) are heartburn and regurgitation. Extensive analysis has characterized heartburn and its responsiveness to proton pump inhibitor (PPI) therapy, but regurgitation has received relatively little attention. This study aimed to evaluate the response of regurgitation to PPI therapy in GERD trials.
  
  
  METHODS
  Studies were identified by systematic searches in PubMed and Embase, as well as searching congress abstracts and the reference lists of Cochrane reviews.
  
  
  RESULTS
  Regurgitation was not an entry criterion or the primary end point in any of the 31 clinical trials reporting the response of regurgitation to PPI treatment in GERD. The definitions of regurgitation and responsiveness varied among trials and over half used investigator assessment of response. Owing to these inconsistencies, no meta-analysis was attempted. In seven placebo-controlled trials of PPI therapy, the therapeutic gain for regurgitation response averaged 17% relative to placebo and was >20% less than that observed for heartburn. Studies comparing PPIs with histamine-2 receptor antagonists or prokinetics found the comparator drug response similar to the placebo response rates seen in the placebo-controlled trials.
  
  
  CONCLUSIONS
  The therapeutic gain with PPIs over placebo or comparator agents for the relief of regurgitation is modest, and considerably lower than for heartburn. Thus, regurgitation is likely to be an important factor for determining incomplete response to PPI treatment in GERD. Future trials would benefit from using regurgitation as a primary end point, applying an unambiguous definition of the symptom and of a positive treatment response, and using a validated patient-reported instrument for regurgitation assessment.
authors.affiliation: Division of Gastroenterology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611-2951, USA. p-kahrilas@northwestern.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kahrilas
authors.forename: Colin W
authors.initials: CW
authors.lastname: Howden
authors.forename: Nesta
authors.initials: N
authors.lastname: Hughes
mesh_terms: D018849:Controlled Clinical Trials as Topic; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006356:Heartburn / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D010528:Peristalsis; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome; D014839:Vomiting / Q000517:prevention & control
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors