Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial

JAMA. 2003 Sep 10;290(10):1337-44. doi: 10.1001/jama.290.10.1337.

Abstract

Context: Diarrhea-associated hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. Most cases are caused by an intestinal infection with Shiga toxin-producing strains of Escherichia coli.

Objective: To determine if administration of an oral agent that binds Shiga toxin could diminish the severity of diarrhea-associated HUS in pediatric patients.

Design, setting, and patients: Multicenter, randomized, double-blind, placebo-controlled clinical trial of 145 children (96 experimental and 49 placebo) aged 6 months to 18 years with diarrhea-associated HUS conducted between July 27, 1997, and April 14, 2001, at 26 tertiary care pediatric nephrology centers in the United States and Canada. Trial included 2 phases, the hospital course for treatment of the acute illness and a 60-day outpatient follow-up period after discharge from the hospital.

Intervention: Patients were assigned to receive the binding agent, 500 mg/kg daily, or cornmeal placebo orally for 7 days in a 2:1 randomization scheme.

Main outcome measures: Combined frequency of death or serious extrarenal events and need for dialysis in the experimental vs placebo group.

Results: A total of 62 patients (43%) were male and 123 (85%) were white. The median age of the patients was 4.2 years. Most patients (59%) were transferred from other hospitals to participating sites. The severity of disease at the time of randomization was comparable in the 2 groups. The prevalence of death or serious extrarenal events was 18% and 20% in the experimental and placebo groups, respectively (P =.82). Dialysis was required in 42% of experimental and 39% of placebo groups (P =.86).

Conclusions: Oral therapy with a Shiga toxin-binding agent failed to diminish the severity of disease in pediatric patients with diarrhea-associated HUS.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Ambulatory Care
  • Child
  • Child, Preschool
  • Diarrhea / drug therapy*
  • Diarrhea / etiology*
  • Diarrhea / microbiology
  • Double-Blind Method
  • Feces / chemistry
  • Feces / microbiology
  • Female
  • Hemolytic-Uremic Syndrome / complications*
  • Hemolytic-Uremic Syndrome / drug therapy*
  • Hemolytic-Uremic Syndrome / microbiology
  • Hospitalization
  • Humans
  • Infant
  • Male
  • Organosilicon Compounds / administration & dosage
  • Organosilicon Compounds / therapeutic use*
  • Shiga Toxins* / genetics
  • Shiga Toxins* / metabolism
  • Trisaccharides / administration & dosage
  • Trisaccharides / therapeutic use*

Substances

  • Organosilicon Compounds
  • SYNSORB Pk
  • Shiga Toxins
  • Trisaccharides