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

Gastroesophageal Reflux Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00131248
• Other study ID #: GERD
• Status: Completed
• Phase: Phase 3
• First received: August 15, 2005
• Last updated: December 12, 2013
• Start date: April 2004
• Est. completion date: March 2008

Study information

• Verified date: December 2013
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 6 Months

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastroesophageal Reflux

Intervention

Drug:
• Metaclopramide

• Ranitidine

• placebo

Locations

Country	Name	City	State
United States	Memorial Hermann Children's Hospital	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bradycardia Episodes/Day		7 days	No