7 Day Comparative Effectiveness in Heartburn Relief and Endoscopic Healing. Randomized Controlled Trial using Omeprazole, Ranitidine, Antacids and Esolgafate, A Pre-Polymerized Cross-Linked Sucralfate (PCLS) Barrier Therapy

Abstract

Chronic symptomatic Abstract Background: Barrier therapy has become an acceptable approach to manage heartburn in erosive gastro-esophageal reflux disease (eGERD). Following ingestion, pre-polymerized cross-linked formulation of standard sucralfate (PCLS, Esolgafate) self-anneals to achieve surface concentrations of sucralfate that is 2400% greater than otherwise possible using standard sucralfate. Main argument: By blocking access of refluxate (bile acid, proteases, hydrochloric acid) to esophageal mucosa, PCLS is as effective as acid controlling therapies within the first 7 days of use. Patients and methods: Multi-center randomized controlled trial in three university medical centers in Bangladesh used a protocol approved and registered with the Medical Research Council. Statistical power of this 4 arm trial required 9 participants per arm. Of 77 patients evaluated for severe dyspepsia, 42 had eGERD and were randomized into four treatment groups with 3 patients lost to follow up, thus leaving 39 for data analysis previously divided into 4 treatment arms that received either 1.5 gram bid sucralfate (PCLS), 20mg bid omeprazole, 150mg bid ranitidine or 30ml qid of aluminum/magnesium hydroxide antacid, 400mg/400mg per 10ml. Each group was assessed for (a) adverse events, (b) symptomatic relief, (c) endoscopic healing and (d) comparative association of relief as a function of healing. Results: Comparable symptomatic relief occurred among 4 groups from 66%-90%, but with divergent healing rates. There was 80% complete healing for PCLS compared to only 30% for omeprazole and 0% for ranitidine and antacids. Conclusions: Relief by healing from PCLS in contrast to relief without healing from acid-controlling therapies implies acid exposure is not the single most significant contributor to eGERD symptoms, but that bile acids and proteases may also be involved. The latter observation is noteworthy when considering causes of nocturnal breakthrough heartburn and refractory GERD.