Medical Treatment for Gastroesophageal Reflux Disease (GERD) in Preterm Infants

• ClinicalTrials.gov Identifier: NCT00131248
• Recruitment Status: Completed
• First Posted: August 17, 2005
• Results First Posted: January 15, 2014
• Last Update Posted: January 15, 2014
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Kathleen Kennedy, The University of Texas Health Science Center, Houston

Tracking Information

• First Submitted Date: August 15, 2005
• First Posted Date: August 17, 2005
• Results First Submitted Date: November 23, 2009
• Results First Posted Date: January 15, 2014
• Last Update Posted Date: January 15, 2014
• Study Start Date: April 2004
• Actual Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 12, 2013): Bradycardia Episodes/Day [ Time Frame: 7 days ]
• Original Primary Outcome Measures (submitted: August 15, 2005): apnea/bradycardia spells/day (comparison between the drug and placebo periods)
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Medical Treatment for Gastroesophageal Reflux Disease (GERD) in Preterm Infants
• Official Title: Cross-over Trial of Medical Treatment for GERD in Preterm Infants

Brief 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Gastroesophageal Reflux

Intervention

• Drug: Metaclopramide
• Drug: Ranitidine
• Drug: placebo

Study Arms

• Anti-reflux Medications, then Placebo (group 1)

  3-day course of anti-reflux medications, followed by 7-day course placebo, followed by 4-day course anti-reflux medications.

  All study medication administered via nipple or orogastric (OG) tube. Metaclopramide (anti-reflux) given in 0.1mg/kg/dose q6hrs, 30min. prior to feedings. Ranitidine, 3mg/kg/dose, q12hrs. Saline placebo at same respective volumes.

  Interventions:

  • Drug: Metaclopramide
  • Drug: Ranitidine
  • Drug: placebo
• Placebo, then Anti-reflux Medications

  3-day course placebo, followed by 7-day course anti-reflux medication, followed by 4-day course placebo.

  All study medication administered via nipple or OG tube. Metaclopramide (anti-reflux) given in 0.1mg/kg/dose q6hrs, 30min. prior to feedings. Ranitidine, 3mg/kg/dose, q12hrs. Saline placebo at same respective volumes.

  Interventions:

  • Drug: Metaclopramide
  • Drug: Ranitidine
  • Drug: placebo

• Publications *: Wheatley E, Kennedy KA. Cross-over trial of treatment for bradycardia attributed to gastroesophageal reflux in preterm infants. J Pediatr. 2009 Oct;155(4):516-21. doi: 10.1016/j.jpeds.2009.03.044. Epub 2009 Jun 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 12, 2013): 18
• Original Enrollment (submitted: August 15, 2005): 34
• Actual Study Completion Date: March 2008
• Actual Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Premature infants < 37 weeks gestation at birth; currently less than 44 weeks postmenstrual age.
• Not currently receiving mechanical ventilation
• Clinical diagnosis of GER and apnea/bradycardia suspected by the clinicians to be related to the GER. (Supporting diagnostic test information, such as upper gastrointestinal series [UGI] studies and pH probes will be recorded but not required for study enrollment.)
• Attending physician plan to begin anti-reflux medications
• Infants may be included in the study if they are on continuous positive airway pressure (CPAP) or methylxanthines for treatment of apnea only if the clinicians are willing to maintain the same regimen for the two-week duration of the study.
• Stable feeding regimen

Exclusion Criteria:

• History of congenital neurological defect
• Imminent discharge (within 2 weeks)
• Parent refusal

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month to 6 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00131248
• Other Study ID Numbers: GERD
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kathleen Kennedy, The University of Texas Health Science Center, Houston
• Original Responsible Party: Not Provided
• Current Study Sponsor: The University of Texas Health Science Center, Houston
• Original Study Sponsor: University of Texas
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kathleen A Kennedy, MD, MPH; University of Texas

• PRS Account: The University of Texas Health Science Center, Houston
• Verification Date: December 2013