28 Day Randomized Double-Blind Placebo Controlled Trial using Pre-Polymerized Cross-Linked Sucralfate Barrier (Esolgafate) for Erosive GERD

Background: Treatment of erosive gastroesophageal reflux disease (eGERD) centers on control of acid pH using proton pump inhibitors (PPI), histamine 2 receptor antagonists (H2RA) and antacids (AA). However, the presence of bile and serine proteases in gastric refluxate, not addressed by PPI, H2RA or AA, is suspected to be associated with onset of Barrett’s esophagus and rise of esophageal adenocarcinoma. Pre-polymerized sucralfate barrier therapy (PPSBT) recognized first by US FDA as a medical device has enhanced bio adherence and blocks access of acid and non-acid irritants to the mucosa.

Aim: To evaluate the efficacy of mucosal protection by PPSBT for the treatment of erosive GERD.

Methods: In a 28 day statistically powered, multi-center randomized double-blind placebo controlled trial, 19 patients with eGERD were randomized to receive PPSBT or placebo. Antacids were available to each group for breakthrough pain. Treatment effect on erosions and eGERD symptoms (heartburn & reflux sensation) were evaluated. Adverse events were assessed.

Results: For patients taking PPSBT, 89% and 78% had relief of heartburn and reflux respectively compared to 25% and 12.5 % of those on placebo. Complete healing occurred in 89% taking PPSBT compared to 25% of those on placebo. No adverse events occurred.

Conclusions: Enhanced mucosal protection by PPSBT demonstrates effective symptom control and erosion healing in patients with eGERD. Acid-indifferent cytoprotection from acid, bile and serine proteases by PPSBT may be a useful adjunct in management of eGERD, and a return to the past for the future.

Summary Box:

What is already known about this subject:

a) Acid irritation is believed to be the sole concern for managing erosive GERD

b) Erosive GERD is best managed by proton pump inhibitors

c) Sucralfate has no role in the therapeutic management of erosive GERD

What are the new findings:

a. Acid, bile acids and proteases are co-equal irritants for erosive GERD

b. Proton pump inhibitors do not address bile acids and proteases

c. Standard sucralfate is too weak to address acid, bile acids and proteases

d. FDA recognized pre-polymerized sucralfate barrier therapy effectively excludes acid, bile acids and proteases from esophageal mucosa in erosive GERD

Keywords: Polymerized sucralfate; Barrier therapy; Erosive GERD; Randomized controlled trial