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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks the best treatment for acid reflux in infants in the NICU by comparing three approaches: using the proton pump inhibitor (PPI) omeprazole, feeding with added rice (AR) formula, or allowing natural maturation without treatment. The trial focuses on determining which method helps infants feed successfully and reduces symptoms like discomfort or feeding difficulties. Infants diagnosed with gastroesophageal reflux disease (GERD), who are fully feeding by mouth but not currently on GERD medications, may be suitable for this trial. As an unphased trial, it offers a unique opportunity to explore innovative treatment options for infants with GERD.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that AR formula is generally safe for babies with acid reflux. Constipation is the main side effect, but most babies tolerate it well. Although it doesn't reduce the amount of acid reflux, it can alleviate symptoms like full-column reflux and coughing.

Omeprazole, a proton pump inhibitor (PPI), is also considered safe, with most side effects being mild, such as stomach issues or skin reactions. However, limited safety information exists about omeprazole for children. The FDA has approved it for treating excessive stomach acid in other conditions.

Both AR formula and omeprazole treat reflux symptoms and have known side effects. Overall, both treatments appear well-tolerated, but consulting a healthcare provider before deciding is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for infant acid reflux because they explore alternatives to standard proton pump inhibitors like Omeprazole. Unlike traditional medications that often work by reducing stomach acid, the Added Rice (AR) Formula offers a novel approach by thickening the infant's diet, potentially minimizing reflux without medication. This dietary intervention could be appealing for parents seeking non-pharmaceutical options. Additionally, the trial includes a natural maturation group, highlighting the potential for some infants to outgrow reflux symptoms with time, offering insights into minimal intervention approaches.

What evidence suggests that this trial's treatments could be effective for infant acid reflux?

This trial will compare AR (added rice) formula with Omeprazole for treating infant acid reflux. Research has shown that adding rice to baby formula can help reduce spit-up in infants. Specifically, one study found that babies experienced fewer spit-ups after using this thicker formula. However, thickened foods are only somewhat effective for treating gastroesophageal reflux (GER) in healthy babies.

Omeprazole, a medicine that reduces stomach acid, is another treatment option in this trial. The evidence about Omeprazole is mixed; some studies show it helps older children with acid reflux, but it might not work as well for babies. In fact, it is often used even though research suggests it may not greatly reduce reflux symptoms in infants and could be harmful. Both treatments have their pros and cons, and the best choice depends on the baby's specific needs and the doctor's advice. ^{2 6 7 8 9}

Who Is on the Research Team?

Sudarshan R [e-mail]

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4052994/

An Antiregurgitation Milk Formula in the Management of ... Moreover, 30.8% of infants with moderate GER showed improvement in the degree of reflux. No infant with severe GER had normal results on the second pH ...

2. aspenjournals.onlinelibrary.wiley.com aspenjournals.onlinelibrary.wiley.com/doi/10.1002/jpen.2566

Comparison of direct effects of rice‐thickened formula vs ... Acutely, thickened formula does not impact acid-specific reflux indices but decreases full-column reflux and cough reflexes.

3. pm.amegroups.org pm.amegroups.org/article/view/6449/html

Validity of anti-reflux formulas as a slightly thick liquid Validity of anti-reflux formulas as a slightly thick liquid: effect of time, caloric density, and refrigerated storage on formula thickness.

4. publications.aap.org publications.aap.org/pediatrics/article/122/6/e1268/68763/The-Effect-of-Thickened-Feed-Interventions-on

The Effect of Thickened-Feed Interventions on ... CONCLUSIONS. This meta-analysis shows that thickened food is only moderately effective in treating gastroesophageal reflux in healthy infants.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4942307/

Efficacy and Tolerance of a New Anti-Regurgitation Formula In all infants, regurgitations improved after 2 weeks. The daily number of regurgitations decreased significantly (-6.3±3.3, p<0.001) including in those ...

6. droracle.ai droracle.ai/articles/284748/what-are-the-risks-associated-with-using-enfamil-infant-formula-ar-anti-reflux-for-infants-with-reflux-issues

Risks of Enfamil AR for Infants with Reflux Enfamil AR formula is generally safe and effective as a first-line treatment for infants with reflux, with the main risks being constipation ...

7. hopkinsmedicine.org hopkinsmedicine.org/health/conditions-and-diseases/gerd-gastroesophageal-reflux-disease-in-children

GERD (Gastroesophageal Reflux Disease) in Children GERD is a more serious and long-lasting form of gastroesophageal reflux (GER). GER is common in babies under 2 years old. Most babies spit up a few times a day ...

8. cps.ca cps.ca/en/documents/position/gastro-esophageal-reflux-in-healthy-infants

Medical management of gastro-esophageal reflux in ... A preliminary report on the efficacy of the Multicare AR-Bed in 3-week-3-month old infants on regurgitation, associated symptoms and acid reflux ...

9. naspghan.org naspghan.org/files/documents/pdfs/training/curriculum-resources/common-outpatient/Reflux%20Slide%20Set%203%20Resident%20Teaching%20Slides%20Reflux.pdf

Gastroesophageal Reflux in Infants – The use of AR formula and formula with added thickener may result in the ... • Anti-reflux surgery may be of benefit in children with confirmed. GERD ...