Verotoxins (VT) produced by certain strains of E. coli (VTEC) are strongly associated with the development of hemolytic uremic syndrome (HUS). Armstrong et al. have shown that VT bind with high affinity to synthetic Pk-trisaccharide receptors coupled to Chromosorb (JID 164:1160-7). Oral ingestion of this substance (called Synsorb-Pk) is safe and well tolerated by healthy adults (JID 171:1042-5). This trial examined the safety, tolerability, and possible efficacy of Synsorb-Pk. Children with diarrhea were eligible if they had documented E. coli O157 (or other VTEC) infection, close contact with an individual with HUS or VTEC infection, or symptoms consistent with VTEC infection (abdominal cramping, bloody diarrhea, rectal prolapse). Eligible subjects received 500 mg/kg of Synsorb-Pk mixed in baby food divided BID for 7 days or an equal volume of corn meal. The primary outcome of interest was the proportion with HUS at day 7 of treatment. Of 364 children enrolled, the mean duration of diarrhea was 3.2 (SD 2.8) days. Eleven subjects were excluded after randomization because of lab evidence at entry of mild HUS or hemolytic anemia (HA), 7 from the Synsorb-Pk group and 4 from the placebo group. Of the remaining 353, there was no difference between groups in the proportion who developed HUS (9/174 vs 10/179). Of those with proven VTEC infection who completed a course of medication, 7/60 Synsorb-Pk vs 9/59 placebo recipients developed HUS. In the restricted subset of those who had entered the study with < 4 days of diarrhea, 4/36 Synsorb-Pk vs 9/37 placebo recipients developed HUS; the relative risk reduction in this secondary analysis was 54%. We conclude that Synsorb-Pk is safe and well tolerated by children with gastroenteritis, and that a rapid diagnostic test is needed for efficient recruitment of those with VTEC infection in future HUS prevention trials. A phase III study is in progress to test the efficacy of Synsorb-Pk in those with confirmed VTEC infection and ≤ 4 days of diarrhea.Funded by Synsorb Biotech Inc., Calgary.