NCT02205541

Brief Summary

The investigators aim to perform the first controlled randomized prospective study using ECZ in pediatric STEC-HUS. This is of great interest as there is still no efficient specific therapy in that potentially devastating disease. Furthermore, published data concerning the use of ECZ in STEC-HUS are controversial, reflecting statistical bias in retrospective or uncontrolled studies, thus emphasizing the need for prospective studies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2015

Typical duration for phase_3

Geographic Reach
1 country

18 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 28, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 31, 2014

Completed
10 months until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

May 4, 2026

Status Verified

April 1, 2026

Enrollment Period

3 years

First QC Date

July 28, 2014

Last Update Submit

April 28, 2026

Conditions

Hemolytic Uremic Syndrome of Childhood

Keywords

EculizumabShiga-toxinhemolytic and uremic syndromepediatric

Outcome Measures

Primary Outcomes (1)

  • the duration in days of extrarenal epuration

    Extrarenal epuration means peritoneal dialysis or hemodialysis, and is assessed at each visit.

    From the inclusion date and assessed up to 13 months

Secondary Outcomes (9)

  • Number of adverse events as a measure of Safety and tolerance of treatment injections (ECZ or placebo)

    At each injection (treatment visits 2, 3, 4, 5, 6 at respectively day 0, 7, 14, 21, 28) and at each follow-up visit (7, 8, 9 respectively at month 2, 7, 13)

  • Adverse reactions related to the treatment (ECZ or placebo)

    At each injection (treatment visits 2, 3, 4, 5, 6 at respectively day 0, 7, 14, 21, 28) and at each follow-up visit (7, 8, 9 respectively at month 2, 7, 13)

  • Duration of Acute Renal Failure (ARF)

    Inclusion Visit (1 at day -3 to -1 ), treatment period (visits 2, 3, 4, 5, 6 respectively at day 0, 7, 14, 21, 28), follow-up period (visits 7, 8, 9 respectively at month 2, 7, 13)

  • Renal sequels

    At 1, 6 and 12 months after last injection of ECZ (follow-up visits 7, 8, 9)

  • Hematological abnormalities

    Inclusion Visit (1 at day -3 to -1), treatment period (visits 2, 3, 4, 5, 6 respectively at day 0, 7, 14, 21, 28), follow-up period (visits 7, 8, 9 respectively at month 2, 7, 13)

  • +4 more secondary outcomes

Study Arms (2)

Eculizumab

EXPERIMENTAL

300mg concentrate for solution for infusion. According to the patient body weight, there will be 3 to 5 injections administered in IV infusion at D0, D7, D14, D21 and D28. Eculizumab (ECZ) will be administrated intravenously as a 30-minute injection.

Drug: Eculizumab

Placebo

PLACEBO COMPARATOR

Infusion of a solution with 5% glucose. The administration scheme will be the same as the Eculizumab arm : there will be 3 to 5 injections at D0, D7, D14, D21 and D28. Placebo will be administrated intravenously as a 30-minute injection.

Drug: Placebo

Interventions

EculizumabDRUG

According to the patient body weight, there will be 3 to 5 injections at D0, D7, D14, D21 and D28. According to the length of initial hospital stay, patients may have the remaining injections in the day ward of the recruiting center. Dosage of ECZ will be based on previous trials using ECZ in pediatric aHUS patients. ECZ or placebo will be administrated intravenously as a 30-minute injection

Also known as: Soloris®
Eculizumab
PlaceboDRUG

According to the patient body weight, there will be 3 to 5 injections at D0, D7, D14, D21 and D28. ECZ or placebo will be administrated intravenously as a 30-minute injection

Also known as: Solution with 5% glucose
Placebo

Eligibility Criteria

Age1 Month - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Pediatric patient (1 month-18 years old)
  • Affected by STEC-HUS defined by :
  • Thrombocytopenia (\<150 000/mm3)
  • Mechanic hemolytic anemia (Hemoglobin \< 10g/dL, haptoglobin \<LLN, lactate dehydrogenase (LDH) \>upper limit of normal (ULN) and/or bilirubin \> ULN, presence of schizocytes)
  • ARF defined by an estimated Schwartz 2009 creatinin clearance \<75ml/min/1,73m²
  • With prodromal diarrhea and/or presence of an enterohemorrhagic strain of Escherichia Coli and/or identification of the Stx 1 or 2 genes in the stool sample or rectal swab
  • Written consent of the 2 parents
  • Female patients of childbearing potential must be practicing an effective, reliable and medically acceptable contraceptive regimen during the entire duration of the study and 5 months after the end of the participation.

You may not qualify if:

  • Neonatal HUS
  • Malignancy
  • Known HIV infection
  • Pregnancy or lactation
  • Identified drug exposure-related HUS
  • Infection-related HUS
  • Known systemic lupus erythematosus or antiphospholipid antibody positivity or syndrome
  • Patient already enrolled in a drug trial
  • Patient with ongoing meningococcal infection
  • Patient affected by aHUS or family history of aHUS
  • STEC-HUS patient with severe multiorgan involvement at diagnostic:
  • Neurological involvement (seizures, coma, focal deficit) with signs of microangiopathy on cerebral Magnetic Resonance Imaging.
  • Cardiac involvement (cardiac failure, ischemic myocarditis, conduction or rhythm troubles)
  • Digestive involvement (severe pancreatitis defined by lipasemia\>500UI/L, severe hepatitis defined by transaminase \>x10ULN and/or prothrombin time\<60%, hemorrhagic colitis, bowel perforation, rectal prolapsus)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

University Hospital

Amiens, 80054, France

Location

University Hospital

Angers, 49100, France

Location

University Hospital

Besançon, 25030, France

Location

Pellegrin Hospital

Bordeaux, 33000, France

Location

Morvan Hospital

Brest, 29609, France

Location

University Hospital

Grenoble, 60107, France

Location

Jeanne de Flandre Hospital

Lille, 59037, France

Location

Mother and Child Hospital

Limoges, 87000, France

Location

Women, Mother and Child Hospital

Lyon, 69500, France

Location

La Timone Hospital

Marseille, France

Location

University Hospital

Montpellier, 34295, France

Location

Mother and Child Hospital

Nantes, 44000, France

Location

Robert Debré Hospital

Paris, 75019, France

Location

Trousseau Hospital

Paris, 75571, France

Location

Necker Hospital

Paris, 75743, France

Location

Anne de Bretagne University Hospital

Rennes, 35056, France

Location

Purpan Children Hospital

Toulouse, 31059, France

Location

Clocheville Hospital

Tours, 37044, France

Location

Related Publications (6)

  • Garnier A, Brochard K, Kwon T, Sellier-Leclerc AL, Lahoche A, Launay EA, Nobili F, Caillez M, Taque S, Harambat J, Michel-Bourdat G, Guigonis V, Fila M, Cloarec S, Djamal-Dine D, de Parscaux L, Allard L, Salomon R, Ulinski T, Fremeaux-Bacchi V, Morin C, Olivier-Abbal P, Colineaux H, Auriol F, Arnaud C, Kieffer I, Brusq C. Efficacy and Safety of Eculizumab in Pediatric Patients Affected by Shiga Toxin-Related Hemolytic and Uremic Syndrome: A Randomized, Placebo-Controlled Trial. J Am Soc Nephrol. 2023 Sep 1;34(9):1561-1573. doi: 10.1681/ASN.0000000000000182. Epub 2023 Jun 12.

    PMID: 37303085RESULT

  • Imdad A, Nelson JR, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2025 Apr 25;4(4):CD012997. doi: 10.1002/14651858.CD012997.pub3.

    PMID: 40277027DERIVED

  • Groussolles M, Winer N, Sentilhes L, Biquart F, Massoud M, Vivanti AJ, Bouchghoul H, Rozenberg P, Olivier P, Desbriere R, Chauleur C, Perrotin F, Coatleven F, Fuchs F, Bretelle F, Tsatsaris V, Salomon LJ, Sananes N, Kayem G, Houflin-Debarge V, Schmitz T, Benoist G, Arnaud C, Ehlinger V, Vayssiere C; Groupe de Recherche en Gynecologie Obstetrique. Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE). Am J Obstet Gynecol. 2022 Aug;227(2):271.e1-271.e13. doi: 10.1016/j.ajog.2022.01.038. Epub 2022 Feb 3.

    PMID: 35123930DERIVED

  • 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.

    PMID: 34219224DERIVED

  • Matrat L, Bacchetta J, Ranchin B, Tanne C, Sellier-Leclerc AL. Pediatric atypical hemolytic-uremic syndrome due to auto-antibodies against factor H: is there an interest to combine eculizumab and mycophenolate mofetil? Pediatr Nephrol. 2021 Jun;36(6):1647-1650. doi: 10.1007/s00467-021-05025-8. Epub 2021 Mar 28.

    PMID: 33774745DERIVED

  • Muff-Luett M, Sanderson KR, Engen RM, Zahr RS, Wenderfer SE, Tran CL, Sharma S, Cai Y, Ingraham S, Winnicki E, Weaver DJ, Hunley TE, Kiessling SG, Seamon M, Woroniecki R, Miyashita Y, Xiao N, Omoloja AA, Kizilbash SJ, Mansuri A, Kallash M, Yu Y, Sherman AK, Srivastava T, Nester CM. Eculizumab exposure in children and young adults: indications, practice patterns, and outcomes-a Pediatric Nephrology Research Consortium study. Pediatr Nephrol. 2021 Aug;36(8):2349-2360. doi: 10.1007/s00467-021-04965-5. Epub 2021 Mar 10.

    PMID: 33693990DERIVED

MeSH Terms

Conditions

Hemolytic-Uremic Syndrome

Interventions

eculizumabSolutionsGlucose

Condition Hierarchy (Ancestors)

UremiaKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesThrombotic MicroangiopathiesThrombocytopeniaBlood Platelet DisordersCytopenia

Intervention Hierarchy (Ancestors)

Pharmaceutical PreparationsHexosesMonosaccharidesSugarsCarbohydrates

Study Officials

  • Arnaud Garnier, MD

    University Hospital, Toulouse

    PRINCIPAL INVESTIGATOR

  • Karine Brochard

    University Hospital, Toulouse

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 28, 2014

First Posted

July 31, 2014

Study Start

June 1, 2015

Primary Completion

June 1, 2018

Study Completion

June 1, 2018

Last Updated

May 4, 2026

Record last verified: 2026-04

Locations

FR(18)