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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kathleen Kennedy, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00131248
First received: August 15, 2005
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Reflux
Drug: Metaclopramide
Drug: Ranitidine
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cross-over Trial of Medical Treatment for GERD in Preterm Infants

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Bradycardia Episodes/Day [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: April 2004
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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.

Drug: Metaclopramide Drug: Ranitidine Drug: placebo

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.

  Eligibility

Ages Eligible for Study:   1 Month to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131248

Locations
United States, Texas
Memorial Hermann Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Kathleen A Kennedy, MD, MPH University of Texas
  More Information

Publications:
Responsible Party: Kathleen Kennedy, Professor - Pediatrics-Neonatology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00131248     History of Changes
Other Study ID Numbers: GERD
Study First Received: August 15, 2005
Results First Received: November 23, 2009
Last Updated: December 12, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metoclopramide
Ranitidine bismuth citrate
Ranitidine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Ulcer Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents

ClinicalTrials.gov processed this record on July 22, 2014