Effect of an Oral Shiga Toxin-Binding Agent on Diarrhea-Associated Hemolytic Uremic Syndrome in Children

A Randomized Controlled Trial

Howard Trachtman, Avital Cnaan, Erica Christen, Kathleen Gibbs, Sanyi Zhao, David W K Acheson, Robert Weiss, Frederick J. Kaskel, Adrian Spitzer, Gladys H. Hirschman

Research output: Contribution to journalArticle

139 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1337-1344
Number of pages8
JournalJournal of the American Medical Association
Volume290
Issue number10
DOIs
StatePublished - Sep 10 2003
Externally publishedYes

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Shiga Toxin
Hemolytic-Uremic Syndrome
Diarrhea
Randomized Controlled Trials
Placebos
Pediatrics
Random Allocation
Dialysis
Shiga-Toxigenic Escherichia coli
Nephrology
Controlled Clinical Trials
Tertiary Healthcare
Acute Kidney Injury
Canada
Oral Administration
Outpatients
Outcome Assessment (Health Care)
Therapeutics
Infection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of an Oral Shiga Toxin-Binding Agent on Diarrhea-Associated Hemolytic Uremic Syndrome in Children : A Randomized Controlled Trial. / Trachtman, Howard; Cnaan, Avital; Christen, Erica; Gibbs, Kathleen; Zhao, Sanyi; Acheson, David W K; Weiss, Robert; Kaskel, Frederick J.; Spitzer, Adrian; Hirschman, Gladys H.

In: Journal of the American Medical Association, Vol. 290, No. 10, 10.09.2003, p. 1337-1344.

Research output: Contribution to journalArticle

Trachtman, Howard ; Cnaan, Avital ; Christen, Erica ; Gibbs, Kathleen ; Zhao, Sanyi ; Acheson, David W K ; Weiss, Robert ; Kaskel, Frederick J. ; Spitzer, Adrian ; Hirschman, Gladys H. / Effect of an Oral Shiga Toxin-Binding Agent on Diarrhea-Associated Hemolytic Uremic Syndrome in Children : A Randomized Controlled Trial. In: Journal of the American Medical Association. 2003 ; Vol. 290, No. 10. pp. 1337-1344.
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AU - Cnaan, Avital

AU - Christen, Erica

AU - Gibbs, Kathleen

AU - Zhao, Sanyi

AU - Acheson, David W K

AU - Weiss, Robert

AU - Kaskel, Frederick J.

AU - Spitzer, Adrian

AU - Hirschman, Gladys H.

PY - 2003/9/10

Y1 - 2003/9/10

N2 - 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.

AB - 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.

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