Recently I was reviewing the “Black Knight scene” from Monty Python’s Holy Grail. This scene in which the Black Knight continues to insist on fighting King Arthur even after losing all of his limbs came to mind as I was reading a recent study (JPGN 2014; 58: 226-36). The blog title comes from an explanation of the scene from John Cleese who intended the scene to mock this philosophy. (Wikipedia link: Black Knight (Monty Python) – Wikipedia, the free encyclopedia)
The study is another trial of a proton pump inhibitor (rabeprazole) for 1- to 11-month old infants with symptomatic GERD. In the discussion the authors note that this is the “fourth DB randomized placebo-controlled study published in the last 4 years that fails to show the efficacy of PPIs to treat symptomatic GERD in infants younger than 1 year.”
If anything, the design of this study should have allowed a therapeutic effect to be witnessed if present. Infants selected for participation (n=268 in the double-blind phase) had been responsive to a 10 mg open-label usage of rabeprazole before randomization. Yet, those infants who continued to receive 5 mg or 10 mg daily fared no better than placebo-treated patients.
The good news: no new safety signals in those who were treated compared to placebo.
The findings of this study are in marked distinction to clinical practice which has embraced PPIs in all age groups. In the same issue of JPGN, using a national database, De Bruyne et al (JPGN 2014; 58: 220-25) show a huge increase in PPI usage over the past decade in the Netherlands, especially in children ages 2 years and younger. From 2004 to 2008, use of PPIs nearly doubled in this population.
The rabeprazole study manuscript which had nearly as many pediatric GI investigators as enrolled patients discusses the potential drawbacks of PPI therapy in infants including enteric infections like Clostridium difficile, lower respiratory infections (e.g.. pneumonia), and “perhaps even an increased incidence of necrotizing enterocolitis in premature infants.” Unlike the Black Knight, after four blows to the PPI cause, the authors recommend yielding on PPIs except under much more stringent criteria (1 of 3):
- Nonimproving symptoms at 1 year of age & resistant to conservative measures
- Presence of underlying conditions that predispose to a natural history of severe chronic unremitting reflux
- Erosive reflux esophagitis proven on endoscopy
Take-home message: PPIs have not been shown to be effective in infants…again!
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