GERD Infant Feeding Therapeutics Trial (GIFT Trial)

Study Overview
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Brief Summary
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The goal of this investigator-initiated, single-center, randomized controlled trial (RCT) is to compare the effects of four weeks of three therapies on clinical and mechanistic outcomes based on pH-Imp testing using a three-arm parallel design in NICU infants with objective GERD diagnosis. The three therapies being compared are natural maturation, proton pump inhibitor (PPI) use, and added rice (AR) formula use. The main goals are: to evaluate and compare the efficacy of the three commonly used treatment interventions used in the NICU for GERD in a randomized controlled manner with the primary endpoint of oral feeding success and absence of troublesome symptoms (as defined below). to characterize the mechanisms of primary end point (success or failure) using pH-Impedance metrics.

Detailed Description
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In consented subjects, eligibility is determined after initial diagnostic 24-hour pH Impedance test. These subjects will be randomized to one of the 3 arms of the study (natural maturation, PPI, AR formula) for 4 weeks of treatment. A second 24-hour pH Impedance test will be done on therapy at 4 weeks or before discharge, whichever occurs first. Primary outcome will also be measured at 4 weeks or at discharge, whichever comes first.

Official Title
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Pathophysiological Evidence Driven Management of GERD in Neonatal ICU Infants: Randomized Controlled Trial

Conditions
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GERD in Infants

Intervention / Treatment
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* Drug: Omeprazole
* Other: AR formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NICU infants of any gestational age who are between 37 - 47 weeks postmenstrual age at inception of the study meeting the following requirements: GERD diagnosis using pH-impedance criteria (Acid Reflux Index ≥ 3% plus at least one of the following: # GER events >70 / day, Symptom Associated Probability ≥ 95%, Discal Baseline Impedance < 900 Ω) Full enteral feeds No current GERD therapies Exclusion Criteria: Known lethal chromosomal abnormalities or complex congenital syndromes Severe neurologic pathologies requiring neuroactive medications or neurosurgery Positive airway pressure or oxygen flow > 4 LPM Upper gastrointestinal malformations requiring surgery

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 8 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Infants will be randomized to one of three arms: Natural maturation, Proton Pump Inhibitor (PPI) treatment, or Added rice (AR) formula. Subjects will be stratified and allocated 1:1:1 based on tube feeds (yes or no) and ARI (3-7% or >7%).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Natural maturation<br>Allows for time for infant maturation without treatment. | |
| Active Comparator: Proton Pump Inhibitor (PPI)<br>Omeprazole will be prescribed for 4 weeks using the dose of 1.5mg/kg/dose daily. | Drug: Omeprazole<br>* Omeprazole will be the PPI prescribed for 4 weeks.<br>* Other names: PPI;|
| Active Comparator: Added Rice (AR) Formula<br>Added rice formula will be ordered as the infant diet for the 4-week treatment period. | Other: AR formula<br>* Added rice formula will be ordered for 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of primary outcome: Improvement or maintenance of oral feeding and/or absence of GERD symptoms (based on feeding method at inception) | Achievement of the primary outcome will be measured by treatment group to determine efficacy. For subjects on full oral feeds at inception, the primary outcome will be met if there is maintenance of oral feeds AND absence of associated GERD symptoms. For subjects receiving any tube feeding at inception, the primary outcome will be met if there is improvement in oral feeding (ratio of oral to tube feeds) OR absence of troublesome symptoms. The metric for measuring the absence of troublesome symptoms will be vomiting <2 times/day or coughing <18 times/day. | At 4 weeks of therapy or discharge, whichever occurs first | 
| Decrease in ARI on treatment | Change in acid reflux index from time one pH impedance study (prior to treatment) to time 2 pH impedance study (during treatment) will be compared among treatment groups. | At time 2 study (4 weeks or prior to discharge, whichever is earliest) | 
| Decreased frequency of GER events on treatment | Change in number of reflux events from time one pH impedance study (prior to treatment) to time 2 pH impedance study (during treatment) will be compared among treatment groups. | At time 2 study (4 weeks or prior to discharge, whichever is earliest) | 
| Improvement (Increase) in distal baseline impedance on treatment | Change in distal baseline impedance from time one pH impedance study (prior to treatment) to time 2 pH impedance study (during treatment) will be compared among treatment groups. | At time 2 study (4 weeks or prior to discharge, whichever is earliest) | 
| Decrease in symptom associated probability on treatment | Change in symptom associated probability from time one pH impedance study (prior to treatment) to time 2 pH impedance study (during treatment) will be compared among treatment groups. | At time 2 study (4 weeks or prior to discharge, whichever is earliest) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proton Pump Inhibitor, pH Impedance, added rice formula