Omeprazole

證據等級: L5

預測適應症: 10 個

Omeprazole: From Peptic Ulcer Disease to Duodenogastric Reflux

One-Sentence Summary

Omeprazole is a proton pump inhibitor (PPI), well established for treating peptic ulcer disease and gastro-oesophageal reflux disease by suppressing gastric acid secretion. The TxGNN model predicts it may also be effective for duodenogastric reflux, but this direction is currently supported by only 1 clinical trial (an imaging-diagnosis study, not a treatment trial) and 20 publications, several of which raise a conflicting safety signal.

Quick Overview

Item	Content
Original Indication	Peptic ulcer disease / gastro-oesophageal reflux disease (well-established PPI indication; no local market-authorisation text is available in this dataset)
Predicted New Indication	Duodenogastric Reflux
TxGNN Prediction Score	99.64%
Evidence Level	L3
Australia Market Status	Not marketed
Number of ARTG Entries	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism-of-action data for this candidate is not available in the Evidence Pack. Based on well-established pharmacological knowledge, omeprazole is a proton pump inhibitor that irreversibly binds the H+/K+-ATPase (“proton pump”) on gastric parietal cells, blocking the final step of acid secretion. Its efficacy in peptic ulcer disease and acid-reflux disorders is well proven.

Duodenogastric reflux (DGR) is mechanistically different from classic acid-reflux disease: it is driven primarily by bile and duodenal content refluxing into the stomach, rather than by gastric acid itself. Acid suppression with omeprazole could plausibly alter gastric emptying and reflux dynamics, which is the rationale behind the TxGNN prediction linking it to DGR.

However, the supporting evidence is mixed rather than reassuring. Several animal studies (e.g. PMID 10389684, PMID 33027361, PMID 8943968) suggest that acid blockade with omeprazole may increase mucosal exposure to bile and even promote gastric carcinogenesis in DGR models — a class effect also reported for other PPIs such as lansoprazole (PMID 15052437). Clinical studies in Barrett’s oesophagus patients (PMID 9824338, PMID 10994616) show omeprazole’s effect on DGR is inconsistent. This mechanistic uncertainty is the main reason the evidence level remains low (L3) despite the very high TxGNN score.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT02685150	N/A	Completed	157	Evaluated endoscopic Tri-Modal Imaging (NBI/AFI/WLI) to distinguish functional dyspepsia from reflux disease (acid or bile). This is a diagnostic-imaging study, not an omeprazole treatment trial — graded C relevance (indirect).

No dedicated treatment trial of omeprazole in duodenogastric reflux was identified.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
9824338	1998	RCT	Gut	Omeprazole 20 mg twice daily and its effect on duodenogastric and duodenogastro-oesophageal bile reflux in Barrett’s oesophagus.
10994616	2000	Cohort	Scand J Gastroenterol	Effect of omeprazole on antral duodenogastric reflux in Barrett oesophagus; suggests DGR may be reduced by omeprazole.
10389684	1999	Animal study	Dig Dis Sci	Gastric acid blockade with omeprazole promotes gastric carcinogenesis induced by duodenogastric reflux in rats — key safety signal.
33027361	2020	Animal study	Acta Cir Bras	Investigated omeprazole and nitrites on gastric mucosa in a rat DGR model, examining a possible protective vs. carcinogenic effect.
8943968	1996	Animal study	Dig Dis Sci	DGR causes growth stimulation of foregut mucosa, potentiated by gastric acid blockade (omeprazole arm included).
15052437	2004	Animal study	Gastric Cancer	Lansoprazole (same PPI class) promotes gastric carcinogenesis in rats with duodenogastric reflux — supports a possible class effect.
16641575	2006	Prospective study	J Pediatr Gastroenterol Nutr	Prospective study of PPI (omeprazole) therapy for oesophageal bile reflux in children.
11552908	2001	Clinical study	Aliment Pharmacol Ther	Influence of pantoprazole (same PPI class) on oesophageal motility and bile/acid reflux in oesophagitis patients.
12836018	2003	Case series	Eur J Pediatr	Describes primary duodenogastric reflux in six children/adolescents unresponsive to classical antacid therapy.
19491829	2009	Clinical study	Am J Gastroenterol	Compares degree of duodenogastroesophageal and acid reflux between PPI responders and non-responders.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: The only clinical trial identified is a diagnostic-imaging study, not a treatment trial, and the literature base is dominated by preclinical/animal work — some of which raises a specific concern that acid suppression with omeprazole may worsen mucosal exposure to bile or promote gastric carcinogenesis in duodenogastric reflux models. Combined with the fact that DGR is primarily a bile-driven (not acid-driven) condition, the mechanistic rationale is uncertain and the evidence level (L3) does not support proceeding at this time.

To proceed, the following is needed:

A dedicated mechanism-of-action (MOA) profile for omeprazole to properly assess mechanistic relevance to DGR
TFDA/PI-sourced safety data (key warnings, contraindications, drug interactions) — currently a blocking data gap
Resolution of the conflicting preclinical carcinogenesis signal (PMID 10389684, PMID 33027361, PMID 15052437) before any clinical development is considered
A prospective clinical trial evaluating omeprazole specifically as a treatment for duodenogastric reflux, rather than for acid-reflux or Barrett’s oesophagus as a secondary endpoint
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.