AR Formula vs Omeprazole for Infant Acid Reflux

(GIFT Trial)

Overseen By Patty Luzader

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Nationwide Children's Hospital

Must not be taking: Neuroactive medications

Disqualifiers: Chromosomal abnormalities, Congenital syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

369 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that participants are not on any current GERD therapies, so you would need to stop taking any GERD medications before joining.

What data supports the effectiveness of the drug omeprazole for treating infant acid reflux?

Research shows that omeprazole, a proton pump inhibitor, is effective in relieving symptoms of gastroesophageal reflux disease (GERD) in children, with studies reporting a median symptom relief rate of 80.4%. It is well-tolerated and has a good safety profile in pediatric patients. ^{1 2 3 4 5}

Is omeprazole safe for use in humans?

Omeprazole, marketed under names like Losec, Prilosec, and Zegerid, is generally considered safe for human use and has been approved by the FDA for various conditions, including gastroesophageal reflux disease (GERD). However, Zegerid contains a high amount of sodium, which may not be suitable for everyone. ^{3 4 5 6 7}

How does the AR Formula and Omeprazole treatment for infant acid reflux differ from other treatments?

The AR Formula and Omeprazole treatment is unique because it combines a dietary approach (AR Formula, which is a thickened formula with added rice) with a medication (Omeprazole, a proton pump inhibitor that reduces stomach acid), offering a dual approach to managing infant acid reflux. This combination may provide both immediate physical relief from reflux through the thickened formula and longer-term acid reduction with Omeprazole, which is not typically seen in standard treatments that often focus on medication alone. ^{1 2 3 5 8}

Research Team

Sudarshan R [e-mail]

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

This trial is for NICU infants with a confirmed GERD diagnosis, who are on full enteral feeds and not currently receiving any GERD treatment. Infants must meet specific pH-impedance criteria to qualify.

Inclusion Criteria

I am not currently on any treatments for acid reflux.

Full enteral feeds

My baby is in the NICU, diagnosed with GERD based on specific tests.

Exclusion Criteria

I need surgery for a stomach or upper intestine problem.

I use a breathing aid with more than 4 liters per minute of air or oxygen.

I do not have any known lethal genetic disorders.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants are randomized to one of three therapies: natural maturation, proton pump inhibitor (PPI) use, or added rice (AR) formula use for 4 weeks.

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on oral feeding success and absence of GERD symptoms.

4 weeks

Treatment Details

Interventions

• AR formula
• Omeprazole

Trial Overview The GIFT Trial compares three treatments for infant GERD over four weeks: natural growth without intervention, Omeprazole (a proton pump inhibitor), and AR formula feeding. The main focus is on successful oral feeding and the absence of troublesome symptoms.

Participant Groups

Group I: Proton Pump Inhibitor (PPI) Active Control 1 Intervention

Omeprazole will be prescribed for 4 weeks using the dose of 1.5mg/kg/dose daily.

Group II: Natural maturation Active Control 1 Intervention

Allows for time for infant maturation without treatment.

Group III: Added Rice (AR) Formula Active Control 1 Intervention

Added rice formula will be ordered as the infant diet for the 4-week treatment period.

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Proton pump inhibitors (PPIs) like omeprazole and lansoprazole are more effective than histamine-2 receptor antagonists for treating gastroesophageal reflux disease (GERD) in children, with studies showing they effectively relieve symptoms and heal erosive esophagitis.

PPIs have a good safety profile in both adults and children, with minimal clinically significant drug interactions, and can be administered in various forms to accommodate children who have difficulty swallowing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment. Gold, BD., Freston, JW.[2018]

Omeprazole, administered as a delayed-release oral suspension, showed an 80.4% median symptom relief rate in children with esophagitis, based on a systematic review of 12 studies.

The treatment resulted in an 84% endoscopic healing rate after 8 weeks and 95% after 12 weeks, indicating high efficacy, although histological healing was lower at 49%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review. Monzani, A., Oderda, G.[2021]

In a study of 18 children with severe gastroesophageal reflux (GER) after failed fundoplication, long-term treatment with omeprazole led to significant improvement in GER symptoms and esophagitis severity, with remission maintained during treatment.

Omeprazole was well-tolerated, with minimal adverse effects, suggesting it is an effective option for managing GER in children before considering further surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omeprazole maintenance therapy for gastroesophageal reflux disease after failure of fundoplication. Pashankar, D., Blair, GK., Israel, DM.[2019]

A study involving 22 healthy male volunteers found that Omeraz and Losec, two omeprazole products, are bioequivalent in terms of absorption, as indicated by similar AUC ratios (1.02 and 1.00) and pharmacokinetic parameters.

Despite the overall bioequivalence, the peak concentration (Cmax) of Omeraz fell outside the FDA's accepted range, suggesting that while the two products are similar, there may be differences in how quickly they reach maximum levels in the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two capsule formulations of omeprazole. Pillai, GK., Salem, MS., Najib, NM., et al.[2013]

In a study of 52 neonates with gastroesophageal reflux disease (GERD), esomeprazole did not significantly reduce the overall symptoms or signs of GERD compared to placebo, indicating limited efficacy in this age group.

However, esomeprazole was well tolerated and significantly decreased the duration of acidic reflux episodes and the time esophageal pH was below 4.0, suggesting it can effectively reduce acid exposure in the esophagus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. Davidson, G., Wenzl, TG., Thomson, M., et al.[2022]

In a Phase III study involving 239 patients with frequent GERD, Zegerid and Losec showed no significant difference in the median time to sustained heartburn relief, with both treatments taking around 60 minutes for Zegerid and 52 minutes for Losec.

However, Zegerid was found to provide sustained total relief within 0-30 minutes for significantly more patients compared to Losec, indicating a potentially faster onset of action despite overall similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec. Walker, D., Ng Kwet Shing, R., Jones, D., et al.[2020]

Zegerid is the first immediate-release proton-pump inhibitor (PPI) approved by the FDA for reducing the risk of upper gastrointestinal bleeding in critically ill patients, making it a significant option for this vulnerable population.

Each dose of Zegerid contains a high amount of sodium (460 mg), which could be a concern for patients on sodium-restricted diets, and it is notably more expensive than traditional delayed-release PPIs like Prilosec.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zegerid--immediate-release omeprazole. [2013]

In a study involving 344 infants aged 1 to 11 months with gastroesophageal reflux disease (GERD), rabeprazole showed initial efficacy in reducing symptoms, but during the double-blind phase, improvements were similar between those continuing rabeprazole and those switched to placebo.

Safety profiles were comparable, with 47% of infants in both the placebo and rabeprazole groups reporting adverse events, indicating that rabeprazole did not introduce new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants with symptomatic GERD. Hussain, S., Kierkus, J., Hu, P., et al.[2015]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Omeprazole maintenance therapy for gastroesophageal reflux disease after failure of fundoplication. [2019]

4. Hungary pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two capsule formulations of omeprazole. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily esomeprazole for the treatment of gastroesophageal reflux disease in neonatal patients. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Zegerid--immediate-release omeprazole. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of delayed release rabeprazole in 1- to 11-month-old infants with symptomatic GERD. [2015]