Medical Treatment for Gastroesophageal Reflux Disease (GERD) in Preterm Infants
Condition: Gastroesophageal Reflux
MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic
Study type: Interventional
Phase: Phase 3

Summary: 
      Study Question: In premature infants with apnea and/or bradycardia attributed to
      gastroesophageal reflux disease (GERD), does treatment with medications (acid blockers and
      motility agents), compared to placebo, reduce the frequency of apnea and bradycardia?

      Background: Many clinicians believe that apnea and bradycardia in preterm infants may be
      caused by gastroesophageal reflux (GER), however, studies have failed to demonstrate even a
      temporal association between episodes of GER and apnea. There have been no prospective
      randomized trials of treatment for GERD in preterm infants with apnea or other symptoms
      attributed to GER.

      Methods: A randomized, cross-over study will be performed. This cross-over design will
      provide the patient's clinician with unbiased information about the patient's response to
      treatment. The clinician can use this information in deciding whether or not to continue
      treatment after the two-week study period.
    

Detailed description: 
      Study Question: In premature infants with apnea and/or bradycardia attributed to GERD, does
      treatment with H2 blockers and prokinetic agents, compared to placebo, reduce the frequency
      of apnea and bradycardia?

      Background: The incidence of gastroesophageal reflux (GER) has been reported in as many as
      50% of healthy term infants and 63% of preterm infants. Anecdotal observations of apnea and
      bradycardia clustered around feedings or with an episode of vomiting have suggested to
      clinicians that apnea and bradycardia in preterm infants may be caused by reflux, however,
      studies have failed to demonstrate even a temporal association between episodes of GER and
      apnea. One retrospective study concluded that anti-reflux medications did not reduce the
      frequency of apnea in premature infants. There have been no prospective randomized trials of
      treatment for GERD in preterm infants with apnea or other symptoms attributed to GER. Despite
      the lack of evidence supporting a causal relationship between GER and respiratory problems in
      preterm infants and the lack of data regarding the efficacy or safety of the treatments for
      GERD, many clinicians continue to believe that GER causes respiratory symptoms in preterm
      infants and these infants are commonly treated with medications for GERD.

      Specific aims: To determine whether medications for GER are effective in reducing respiratory
      symptoms attributed to GER.

      Methods: A randomized, controlled masked cross-over study will be performed. The cross-over
      design will prevent evaluation of long-term outcomes but will increase the power to evaluate
      short-term outcomes by using the patient as his/her own control. This cross-over design will
      also provide the patient's clinician with unbiased information about the patient's response
      to treatment. The clinician can use this information in deciding whether or not to continue
      treatment after the two-week study period. This approach for making therapeutic decisions in
      individual patients has been described as an "N of 1" trial.
    

Intervention name(s): Metaclopramide; Ranitidine; placebo
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Metoclopramide; Ranitidine; Ranitidine bismuth citrate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment