Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial

Abstract

Introduction: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.

Methods: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.

Results: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.

Discussion: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Graphical abstract

Figure 1.

Patient distribution. PPI, proton-pump inhibitor.

Figure 2.

Mean absolute symptom score values, results of primary analysis, and use of rescue medication and Poliprotect on demand. (a) Mean absolute values of symptom severity score, as measured by means of a 100 mm visual analog scale (VAS; from no symptoms equal to 0 mm to overwhelming symptoms equal to 100 mm). From V2 to V3, depicted with a colorful background, the comparison treatment (PPI) and blinding were both removed, and all patients were administered Poliprotect verum only, on demand. The I bars represent standard error. (b) Difference in absolute change in the VAS symptom severity score from baseline to day 13 (V0–V1) between the omeprazole group and the Poliprotect group and relative 95% confidence interval, supporting the hypothesis that Poliprotect was noninferior to omeprazole. In both the per-protocol and intention-to-treat populations, the inferiority hypothesis is rejected by means of the unilateral unpaired Student t test shifted by −11 (minus the noninferiority threshold) on the change in the symptom score between baseline and visit 1 (P = 0.020 and P = 0.008 for noninferiority, respectively). (c) Number of sachets of rescue medication used during the indicated study periods. (d) Number of tablets of Poliprotect (verum or placebo) used on demand. *P < 0.05. PPI, proton-pump inhibitor.

Figure 3.

Analysis of microbiome. (a) Color-coded box plots showing α-diversity estimators, measured for each group at different time points. (b) PCoA plot of bacterial β-diversity based on Bray-Curtis dissimilarity and weighted UniFrac distance according to individual health status. For each group, the 95% confidence interval has been drawn. Numbers between parentheses represent the percentage of the total variance explained by the principal coordinates. (c) Box plots showing the distribution of differences in the interindividual distances over time (V2–V0) for both considered beta measures. (d) Color-coded box plots showing the distribution of bacterial species that were significantly enriched at V2 with respect to V0. A P value ≤ 0.05 was considered statistically significant. PPI, proton-pump inhibitor.