HIGH-DISPERSION SILICON DIOXIDE FOR THE TREATMENT OF ACUTE DIARRHEA: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Abstract

INTRODUCTION: Acute diarrhea imposes a substantial burden on emergency departments (ED) globally. While oral rehydration solution (ORS) prevents dehydration, it does not reduce symptom duration. Current pharmacological options are limited by safety concerns (e.g., loperamide) or modest efficacy. We evaluated the efficacy and safety of high-dispersion silicon dioxide (HDSD), an enterosorbent with a high specific surface area (approximately 300 m2/g), for the treatment of acute watery diarrhea in adults. MATERIAL AND METHODS: We conducted a multicenter, double-blind, placebo-controlled trial across three Turkish EDs (October–December 2025). Adults presenting within 48 hours of acute diarrhea onset [? 3 watery stools/day, Bristol Stool Scale (BSS) 5–7] were randomized 1:1 to HDSD (3 g three times daily) or matched placebo for up to 5 days. Primary outcome: time from treatment initiation to the onset of a 24-hour period during which the patient reported no loose or watery stools (BSS < 5) and rated overall well-being as ? ? 3 on a 10-point numerical rating scale (NRS). Time-to-event data were analyzed using Kaplan–Meier survival analysis and Cox proportional hazards regression; longitudinal symptom trajectories were evaluated by repeated-measures analysis of variance (RM-ANOVA) and confirmed with generalized estimating equations (GEE) as a prespecified sensitivity analysis. RESULTS: Among 194 randomized patients (99 HDSD, 95 placebo), HDSD accelerated recovery. Median recovery time was 21 hours [95% confidence interval (CI): 21–23] vs 72 hours (95% CI: 70–76); absolute difference 51 hours (p < 0.001). Patients receiving placebo had a markedly lower rate of recovery compared with HDSD at any given time point [hazard ratio (HR) = 0.05; 95% CI: 0.03–0.07; p < 0.001]; equivalently, HDSD was associated with an approximately 20-fold higher recovery rate than placebo (HR = 20.0; 95% CI: 14.3–27.9). At 24 hours, 66.7% of HDSD patients had recovered vs none receiving placebo. Abdominal pain visual analog scale (VAS), gastrointestinal (GI) symptoms [Gastrointestinal Symptom Rating Scale (GSRS)], and stool consistency (BSS) all improved faster with HDSD across all timepoints (p < 0.001). The only treatment-related adverse event (AE) was mild-to-moderate constipation in 11 patients (11.1%) receiving HDSD; no serious AEs occurred in either group. CONCLUSIONS: In adults with acute diarrhea, HDSD reduced recovery time by 51 hours compared to placebo, a 71% reduction. This effect substantially exceeds published data for other enterosorbents. Given its favorable safety profile and non-systemic mechanism, HDSD merits consideration as first-line adjunctive therapy in acute gastroenteritis (AGE) management. © 2026 Via Medica