Effect of an Oral Shiga Toxin–Binding Agent on Diarrhea-Associated Hemolytic Uremic Syndrome in Children: A Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 290; no. 10; pp. 1337 - 1344
• Main Authors: Trachtman, Howard, Cnaan, Avital, Christen, Erica, Gibbs, Kathleen, Zhao, Sanyi, Acheson, David W. K, Weiss, Robert, Kaskel, Frederick J, Spitzer, Adrian, Hirschman, Gladys H, for the Investigators of the HUS-SYNSORB Pk Multicenter Clinical Trial
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 10.09.2003
• Subjects: Administration, Oral; Adolescent; Ambulatory Care; Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Biological and medical sciences; Child; Child, Preschool; Children & youth; Diarrhea; 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; Human bacterial diseases; Humans; Infant; Infectious diseases; Kidneys; Male; Medical disorders; Medical sciences; Medical treatment; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Organosilicon Compounds - administration & dosage; Organosilicon Compounds - therapeutic use; Renal failure; Shiga Toxins - genetics; Shiga Toxins - metabolism; Trisaccharides - administration & dosage; Trisaccharides - therapeutic use; Performance evaluation; Kaplan Meier estimator; Glomerular filtration; Escherichia coli; Multicenter study; Cardiovascular disease; Infant; Hemopathy; Randomization; Hemolytic anemia; Bacteria; Intestinal disease; Complication; Child; Shiga like toxin; Enterobacteriaceae; Human; Hypertension; Kidney disease; Urinary system disease; Statistical analysis; Hemolytic uremic syndrome; Treatment efficiency; Diarrhea; Controlled therapeutic trial; Exploration; Symptomatology; Treatment; Adolescent; Renal failure; Double blind study; Digestive diseases; Proteinuria
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.290.10.1337

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.