Vonaprazan Versus Esomeprazole for Healing of LA Grade B or Higher Esophagitis After POEM: A Non-Inferiority Randomized Trial

Peroral Endoscopic Myotomy (POEM) is a well-established treatment for achalasia; however, it is frequently associated with gastroesophageal reflux disease (GERD), with many patients developing LA grade B or higher esophagitis. Proton pump inhibitors (PPIs) like Esomeprazole are the standard treatment, but Vonaprazan, a potassium-competitive acid blocker (P-CAB), offers superior acid suppression and may provide enhanced healing in post-POEM reflux esophagitis.

Primary Objective:

• To compare the healing rates of LA grade B or higher reflux esophagitis at 8 weeks in patients receiving Vonaprazan 20 mg versus Esomeprazole 40 mg.

Secondary Objectives

* To assess improvement in reflux symptoms using the GERD-Q score at 8 weeks.
* To evaluate the incidence of adverse events in each treatment group.

Primary Objective • To compare the healing rates of LA grade B or higher reflux esophagitis at 8 weeks in patients receiving Vonaprazan 20 mg versus Esomeprazole 40 mg.

Secondary Objectives

* To assess improvement in reflux symptoms using the GERD-Q score at 8 weeks.
* To evaluate the incidence of adverse events in each treatment group.

Study Type:

• Randomized, Open-Label, Two-Arm, Non-Inferiority Trial

Randomization and Blinding:

* Randomization: 1:1 ratio between Vonaprazan 20 mg and Esomeprazole 40 mg.
* Stratification: Based on LA grade (B vs. C/D) at baseline.
* Blinding: Open-label study, but outcome assessors will be blinded.

Study Timeline:

1. All post-POEM patients receive Esomeprazole 40 mg for 2 months.
2. PPI is discontinued for 1 month (to allow reflux esophagitis to develop if persistent GERD exists).
3. At 3 months post-POEM, patients with LA grade B or higher esophagitis (on follow-up endoscopy) are randomized to either Vonaprazan 20 mg or Esomeprazole 40 mg for 8 weeks.
4. At 8 weeks post-randomization (5 months post-POEM), healing of esophagitis is assessed.

   Study Arms:
   * Arm A: Vonaprazan 20 mg once daily for 8 weeks
   * Arm B: Esomeprazole 40 mg once daily for 8 weeks
5. Inclusion and Exclusion Criteria

Inclusion Criteria:

* Age ≥18 years
* History of POEM for achalasia
* Endoscopic confirmation of LA grade B, C, or D reflux esophagitis at 3 months post-POEM
* GERD symptoms (heartburn, regurgitation) for ≥4 weeks
* Willingness to provide informed consent and comply with study procedures

Exclusion Criteria:

* History of prior anti-reflux surgery
* Presence of Barrett's esophagus, esophageal stricture, or malignancy
* Severe gastroparesis or esophageal motility disorder unrelated to achalasia
* Pregnancy or breastfeeding
* Severe hepatic or renal impairment (ALT/AST \>3× ULN, eGFR \<30 mL/min)
* Regular use of NSAIDs, steroids, or anticoagulants affecting esophageal healing

Study Procedures:

Baseline Assessment (3 Months Post-POEM, Before Randomization)

* Upper GI Endoscopy: Confirmation of LA grade B or higher reflux esophagitis.
* GERD-Q Score assessment.
* Randomization to Vonaprazan 20 mg or Esomeprazole 40 mg. Follow-Up (Week 4 - Interim Visit)
* GERD-Q Score assessment.

End-of-Treatment (Week 8 - Final Visit, 5 Months Post-POEM)

* Upper GI Endoscopy to assess healing of reflux esophagitis.
* GERD-Q Score reassessment.
* Final adverse event reporting.

Primary Outcome:

• Endoscopic healing of reflux esophagitis at 8 weeks (absence of LA grade B or higher esophagitis).

Secondary Outcomes:

* Improvement in GERD-Q scores at 8 weeks.
* Incidence of adverse events (e.g., headache, diarrhea, hypomagnesemia).

Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years
* History of POEM for achalasia
* Endoscopic confirmation of LA grade B, C, or D reflux esophagitis at 3 months post-POEM
* GERD symptoms (heartburn, regurgitation) for ≥4 weeks
* Willingness to provide informed consent and comply with study procedures

Exclusion Criteria:

* History of prior anti-reflux surgery
* Presence of Barrett's esophagus, esophageal stricture, or malignancy
* Severe gastroparesis or esophageal motility disorder unrelated to achalasia
* Pregnancy or breastfeeding
* Severe hepatic or renal impairment (ALT/AST \>3× ULN, eGFR \<30 mL/min)
* Regular use of NSAIDs, steroids, or anticoagulants affecting esophageal healing