Phase III Randomized Study of SYNSORB Pk in Children With E. Coli-Associated Hemolytic Uremic Syndrome

Phase III Randomized Study of SYNSORB Pk in Children With E. Coli-Associated

OBJECTIVES: I. Determine the effect of SYNSORB Pk therapy on mortality and frequency of severe extrarenal complications observed in children with acute stage E. coli-associated hemolytic uremic syndrome.

II. Determine the effect of SYNSORB Pk therapy on the need for the duration of dialysis in these patients.

III. Determine the effect of SYNSORB Pk therapy on the recovery of renal function and resolution of urinary abnormalities in these patients.

Study Overview

• Status: Terminated
• Conditions: Hemolytic Uremic Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: SYNSORB Pk

Detailed Description

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are randomized to receive either SYNSORB Pk or placebo.

Patients receive oral SYNSORB Pk or placebo three times daily for 7 days. Patients are followed on days 7, 14, 28, and 60 after discharge from the hospital.

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R7
      • University of Alberta
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Children's Hospital of Denver
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • Alfred I. Dupont Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Augusta, Georgia, United States, 30912-3620
      • Medical College of Georgia Hospital and Clinics
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5265
      • Indiana University Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Boston Floating Hospital Infants and Children
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson Medical School
    • Paterson, New Jersey, United States, 07503
      • Children's Hospital at St. Joseph's
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Buffalo, New York, United States, 14222
      • Children's Hospital of Buffalo
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11790-7775
      • State University of New York Health Sciences Center - Stony Brook
    • The Bronx, New York, United States, 10461
      • Jack D. Weiler Hospital of the Albert Einstein College of Medicine
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Bowman Gray School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43205-2696
      • Ohio State University Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9162
      • West Virginia University Hospitals
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-4108
      • University of Wisconsin Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Clinically diagnosed E. coli-associated diarrhea-associated hemolytic uremic syndrome (HUS)
• Diarrheal prodrome within 7 days before onset of disease
• No HUS associated with the following: Hereditary Post-bone marrow transplantation Streptococcus pneumoniae infection
• No prior catastrophic complications

--Patient Characteristics--

• Hematopoietic: Thrombocytopenia less than 140,000/mm3 Fragmented red blood cells
• Renal: Renal involvement (hematuria, proteinuria, or azotemia) No underlying glomerular disease
• Other: HIV negative No pre-existing structural abnormality or dysmotility syndrome of the gastrointestinal tract No inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYNSORB Pk; Oral Shiga toxin-binding agent (500 mg/kg/day)	Drug: SYNSORB Pk; Other Names: Oral Shiga Toxin Binding Agent
Placebo Comparator: Placebo; Cornmeal placebo	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to death or serious extrarenal events	60 days
Time to dialysis	60 days

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Long Island Jewish Medical Center
• Investigators: Study Chair: Howard Trachtman, Long Island Jewish Medical Center

Publications and helpful links

General Publications

• Imdad A, Mackoff SP, Urciuoli DM, Syed T, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Jul 5;7(7):CD012997. doi: 10.1002/14651858.CD012997.pub2.
• Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DW, Weiss R, Kaskel FJ, Spitzer A, Hirschman GH; Investigators of the HUS-SYNSORB Pk Multicenter Clinical Trial. 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 1997
• Primary Completion (Actual): April 14, 2001
• Study Completion (Actual): April 14, 2001

Study Registration Dates

• First Submitted: October 18, 1999
• First Submitted That Met QC Criteria: October 18, 1999
• First Posted (Estimate): October 19, 1999

Study Record Updates

• Last Update Posted (Actual): June 1, 2017
• Last Update Submitted That Met QC Criteria: May 30, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: rare disease; bacterial infection; immunologic disorders and infectious disorders; renal and genitourinary disorders; hemolytic uremic syndrome; E. coli infection
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Hematologic Diseases; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Thrombotic Microangiopathies; Uremia; Syndrome; Azotemia; Hemolysis; Hemolytic-Uremic Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Synthesis Inhibitors; Shiga Toxins
• Other Study ID Numbers: 199/13923; LIJMC-96-5-186 (Other Identifier: Long Island Jewish Medical Center); R01DK052147 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No