Gastroesophageal Reflux
Conditions
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.
Interventions
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Months to 6 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Bradycardia Episodes/Day | 7 days |
Countries
United States
Participant flow
Recruitment details
participants = premature infants, \<36 weeks gestation at birth, recruited from NICU at a hospital in Houston, Texas,USA, between 2004-2009
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Intervention 1 (3-day Course) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 17 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 0.1 years STANDARD_DEVIATION 0.06 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Bradycardia Episodes/Day
Time frame: 7 days
Population: 18 participants originally enrolled, 1 withdrew, leaving 17 participants analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Medications | Bradycardia Episodes/Day | 4.6 episodes per day | Standard Deviation 3.1 |
| Placebo | Bradycardia Episodes/Day | 3.6 episodes per day | Standard Deviation 2.7 |