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

December 12, 2013 updated by: Kathleen Kennedy, The University of Texas Health Science Center, Houston

Cross-over Trial of Medical Treatment for GERD in Preterm Infants

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

18

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Memorial Hermann Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 6 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Drug: placebo
Drug: Ranitidine
Drug: Metaclopramide
Other: 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.
Drug: placebo
Drug: Ranitidine
Drug: Metaclopramide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Bradycardia Episodes/Day
Time Frame: 7 days
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

August 15, 2005

First Submitted That Met QC Criteria

August 15, 2005

First Posted (Estimate)

August 17, 2005

Study Record Updates

Last Update Posted (Estimate)

January 15, 2014

Last Update Submitted That Met QC Criteria

December 12, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GERD (Other Identifier: Alias Study Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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