Please select the eligibility criteria that correspond to the clinical trial below.
Title: Early Treatment With the Monoclonal C5 Antibody Eculizumab in Pediatric Patients Affected by Shiga-toxin Related Hemolytic and Uremic Syndrome: A Phase III Prospective Randomized Controlled Therapeutic Trial Versus Placebo
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.


Options:
A: Inclusion Criteria:

1. Age \<18.0 years;
2. STEC infection \[positive culture OR antigen OR polymerase chain reaction test for Stx/gene\];
3. Day of illness 1-10: Children who develop HUS will do so by day #14 of illness;8 restricting enrolment to the first 10 days will ensure all participants are at risk of HUS.

Exclusion Criteria:

1. Evidence of evolving HUS: A) Hematocrit \<30% OR B) Platelet count \<150 x 109/L;
2. Responsible physician desires patient admission (therefore unable to randomize);
3. Unable to contact family within 48 hours of positive stool test;
4. Patient with history of atypical HUS;
5. Chronic disease limiting fluid volumes administered (e.g. impaired cardiac function)
B: Inclusion Criteria:

1. Age of ≥ 1 to \< 10 y.
2. Signed informed consent from the parent(s)/legal guardian with assent from the subject as appropriate by age and regulatory guidance.
3. Bloody diarrhea based upon history or presentation (by visual inspection).
4. Detection of Stx2 in stool based on enzyme immunoassay (EIA) and/or stx2 based on PCR before randomization.

   NOTE: The basis for accepting a positive test for stx2 by EIA is based on taking as valid the results yielded from an EIA whose sensitivity and specificity are greater than 98.7% and 100%, respectively (according to the description in the insert) as per recommendation given by the NRL. The Sponsor will select the investigational sites that have in their laboratory such EIA test used in the STEC diagnostic routine algorithm. (Appendix 6).
5. For children between 1 to 5 years old: weight for length/height between percentiles 3 (\< 2 z score) and 97 (\> 2 z score) corresponding to age (according to the reference tables "WHO Child Growth Standards".
6. For children ≥ 5 years: Body mass index (BMI) between percentiles 3 (\<2 z score) and 97 (\> 2 z score) corresponding to age (according to the reference tables "WHO Child Standards, Appendix 4)

Exclusion Criteria:

1. Any laboratory findings compatible with the development of HUS:

   * Microangiopathic hemolytic anemia defined as LDH above the ULN for age with the finding of schistocytes on peripheral smear and a negative Coomb's test, and/or
   * Thrombocytopenia: platelet count \< 150 × 103/μL, and/or
   * Renal failure: serum creatinine \> ULN adjusted for age and gender criteria despite correction of hypovolemia, and/or hematuria, and/or proteinuria (Table 7.1)11 NOTE: Laboratory results must be obtained within 24 h before the 1st study drug administration; there must be no clinical signs and symptoms of HUS at the time laboratory assessments are obtained. If there is any change in clinical presentation in the 24 h before the 1st study drug administration, laboratory assessments are to be repeated and results reviewed before study drug administration.

   NOTE: Laboratory and physical examination results must indicate normal hydration before the 1st study drug administration.
2. A history of chronic/recurrent hemolytic anemia, thrombocytopenia, or chronic renal failure.
3. A family history of aHUS.
4. Anuria or oliguria after hypovolemia is corrected.
5. Evidence of clinically significant chronic active disease not medically controlled.
6. History of anaphylaxis, prior administration of equine serum (eg, antitetanus serum or anti-ophidic serum, or anti-arachnid toxin serum), or allergic reaction to contact with, or exposure to, horses.
7. Family relation or work relation with a member of the personnel of the research group.

   -
C: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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)
D: 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)

Answer: C