Gastroesophageal Reflux Disease
Conditions
Keywords
infant, esophagitis, neonate, GERD
Brief summary
The overall purpose of the investigator's study is to evaluate the causes of and treatment for feeding difficulty in infants with Gastro-esophageal Reflux Disease (GERD). New treatments can be possible only if the cause is known. Many infants have GERD and feeding difficulties, such as sucking and swallowing problems, vomiting, or delayed emptying of the stomach. Some of these infants have difficulty in protecting their airway during feeding or during reflux, and as a result can breathe fluid into their lungs or hold their breath. Most GERD treatments are done based on experience, but there is no scientific proof that these methods work for infants. GERD and feeding difficulties can lead to longer hospitalization and more stress for the family. In this clinical trial, the investigators are developing new methods to help with diagnosis as well as defining better treatment strategies in relieving GERD and GERD complications.
Detailed description
Gastroesophageal reflux disease (GERD) and its troublesome complications constitute serious diagnostic and management challenges to the development of safe feeding and airway protection strategies among infants convalescing in the neonatal intensive care units; thus contributing to prolonged lengths of stay, recurrent hospitalizations, and death. GERD is frequently diagnosed by inadequate criteria, and the relative risks, benefits and indications of GERD therapies are unclear. Significant gaps in knowledge exist in understanding the complex causal or adaptive aerodigestive protective reflex mechanisms implicated in GERD in infants. The long-term goal is to improve digestive health, nutrition, and infant development through the design of simplified personalized treatment paradigms by better understanding the pathophysiology of aerodigestive reflexes. The current objective is to conduct a prospective single center randomized blinded controlled trial comparing the short term effects of the investigators innovative feeding strategy bundle (study approach) versus standard feeding approach (conventional approach).
Interventions
OTHERStudy Arm - acid suppression plus feeding bundle
* Omeprazole 0.5-1.5 milligrams/kilogram/dose twice a day (BID) * Total fluid volume restriction (120-140 milliliters/kilogram/day) * Feeding duration over 30 minutes * Infant feeds with right side down * Infant is placed on back following feeds
OTHERConventional arm - acid suppression only
-Omeprazole 0.5-1.5 milligrams/kilogram/dose twice a day (BID)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Ohio State University
Sudarshan Jadcherla
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
34 Weeks to 60 Weeks
Healthy volunteers
No
Inclusion criteria
* Hospitalized infants with aerodigestive or GERD symptoms * Gestational age ≤42 weeks * Premature infants are eligible at 34 weeks postmenstrual age (PMA) * Enteral or Oral Fed * Average daily total feeding volume ≥ 150ml/kg/day * Room air or supplemental oxygen of ≤1 liter/minute (LPM) and/or ≤ 35% by nasal cannula
Exclusion criteria
* Known genetic, metabolic or syndromic disease * Neurological diseases such as Grade 3 or 4 intraventricular hemorrhage (IVH) or intracranial hemorrhage (ICH) and perinatal asphyxia * Gastrointestinal malformations and surgical gastrointestinal conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CLINICAL OUTCOME OF FEEDING SUCCESS | Up to 5 weeks after enrollment | The primary endpoint is the feeding success defined as achieving full oral feeds (defined as no need for tube feeds to maintain hydration and nutrition) and/or a \>/= 6 point decrease from baseline symptom score as described by the Infant-Gastro-Esophageal Reflux Questionnaire-Revised. The minimum score is 0 (no symptoms) and the maximum score is 42 (maximum symptoms). Any total score greater than or equal to 16 is considered abnormal. |
| MOTILITY OUTCOMES: Presence of Esophageal Peristaltic Reflexes | 5 weeks | This is part of Aim 2 of this RCT, which is a mechanistic outcome designed to understand the reasons for the clinical outcome. Presence of peristaltic reflex mechanisms elicited upon esophageal provocation during esophageal manometry were compared within the groups, week-5 vs. week-0. Odds ratios (ORs) with 95% confidence interval (CI) are reported from Generalized Estimation Equation models. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CLINICAL OUTCOMES: Growth Outcome Measure | at 5 weeks | Growth: The investigators will measure and track weight growth velocity during the study period |
| CLINICAL OUTCOME: Development Outcome Measures | Up to 1 year age | Feeding Milestones: The investigators will track feeding method at 1 year. |
| CLINICAL OUTCOME: Respiratory Outcome Measures | at discharge | Supplemental oxygen requirement at discharge was recorded for both groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Treated with omeprazole. This group of subjects will have prescribed restricted feeding volumes, monitored feeding duration time and positioning restrictions
Study: -Omeprazole 0.75-1.5 milligrams/kilogram/dose twice a day (BID)
* Total fluid volume restriction (120-140 milliliters/kilogram/day)
* Feeding duration over 30 minutes
* Infant feeds with right side down
* Infant is placed on back following feeds | 40 |
| Conventional Treated with omeprazole. This group of subjects will receive the current standard treatment for Gastro-esophageal reflux disease (GERD) which includes use of acid suppressive medication with no restrictions of the feeding volume, duration or positioning. | 36 |
| Total | 76 |
Baseline characteristics
| Characteristic | Study | Conventional | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 40 Participants | 36 Participants | 76 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.7 weeks STANDARD_DEVIATION 4.3 | 11.1 weeks STANDARD_DEVIATION 4.5 | 10.9 weeks STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 32 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) White | 27 Participants | 30 Participants | 57 Participants |
| Region of Enrollment United States | 40 participants | 36 participants | 76 participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 37 Participants |
| Sex: Female, Male Male | 21 Participants | 18 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 36 |
| other Total, other adverse events | 0 / 40 | 0 / 36 |
| serious Total, serious adverse events | 0 / 40 | 0 / 36 |
Outcome results
Primary
CLINICAL OUTCOME OF FEEDING SUCCESS
The primary endpoint is the feeding success defined as achieving full oral feeds (defined as no need for tube feeds to maintain hydration and nutrition) and/or a \>/= 6 point decrease from baseline symptom score as described by the Infant-Gastro-Esophageal Reflux Questionnaire-Revised. The minimum score is 0 (no symptoms) and the maximum score is 42 (maximum symptoms). Any total score greater than or equal to 16 is considered abnormal.
Time frame: Up to 5 weeks after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study | CLINICAL OUTCOME OF FEEDING SUCCESS | 33 percentage of participants |
| Conventional | CLINICAL OUTCOME OF FEEDING SUCCESS | 44 percentage of participants |
p-value: 0.28Chi-squared
Primary
MOTILITY OUTCOMES: Presence of Esophageal Peristaltic Reflexes
This is part of Aim 2 of this RCT, which is a mechanistic outcome designed to understand the reasons for the clinical outcome. Presence of peristaltic reflex mechanisms elicited upon esophageal provocation during esophageal manometry were compared within the groups, week-5 vs. week-0. Odds ratios (ORs) with 95% confidence interval (CI) are reported from Generalized Estimation Equation models.
Time frame: 5 weeks
Population: Participants must have motility evaluations completed at week 0 and week 5 and have PPI washout period prior to week 5 evaluation (49 infants had follow up motility studies at week 5 of whom 40 infants had PPI washout while the other 9 remained on PPI due to parental refusal to stop).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study | MOTILITY OUTCOMES: Presence of Esophageal Peristaltic Reflexes | 0.5 odds ratio, week-5 vs. week-0 |
| Conventional | MOTILITY OUTCOMES: Presence of Esophageal Peristaltic Reflexes | 0.7 odds ratio, week-5 vs. week-0 |
Comparison: Generalized Estimation Equation (GEE) model was used for the comparison of differences between intervention groups from week 0 to week 5 for peristaltic response frequency.p-value: 0.9995% CI: [0.4, 1.6]Generalized Estimation Equation
Secondary
CLINICAL OUTCOME: Development Outcome Measures
Feeding Milestones: The investigators will track feeding method at 1 year.
Time frame: Up to 1 year age
Population: Those subjects with follow up data available at 1 year of age
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study | CLINICAL OUTCOME: Development Outcome Measures | PO | 17 Participants |
| Study | CLINICAL OUTCOME: Development Outcome Measures | Transition (PO + tube) | 4 Participants |
| Study | CLINICAL OUTCOME: Development Outcome Measures | Tube | 1 Participants |
| Conventional | CLINICAL OUTCOME: Development Outcome Measures | PO | 20 Participants |
| Conventional | CLINICAL OUTCOME: Development Outcome Measures | Transition (PO + tube) | 0 Participants |
| Conventional | CLINICAL OUTCOME: Development Outcome Measures | Tube | 2 Participants |
p-value: 0.11Chi-squared
Secondary
CLINICAL OUTCOME: Respiratory Outcome Measures
Supplemental oxygen requirement at discharge was recorded for both groups
Time frame: at discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study | CLINICAL OUTCOME: Respiratory Outcome Measures | 7 Participants |
| Conventional | CLINICAL OUTCOME: Respiratory Outcome Measures | 9 Participants |
p-value: 0.49Chi-squared
Secondary
CLINICAL OUTCOMES: Growth Outcome Measure
Growth: The investigators will measure and track weight growth velocity during the study period
Time frame: at 5 weeks
Population: Weight not available for three patients in conventional and one patient in study group at time 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study | CLINICAL OUTCOMES: Growth Outcome Measure | 27.6 grams/day | Standard Deviation 11.1 |
| Conventional | CLINICAL OUTCOMES: Growth Outcome Measure | 26.5 grams/day | Standard Deviation 7.2 |
p-value: 0.64t-test, 2 sided