<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02205541</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/13/7052</org_study_id>
    <secondary_id>PHRC 13-0060</secondary_id>
    <secondary_id>2014-001169-28</secondary_id>
    <nct_id>NCT02205541</nct_id>
  </id_info>
  <brief_title>Eculizumab in Shiga-toxin Related Hemolytic and Uremic Syndrome Pediatric Patients - ECULISHU</brief_title>
  <acronym>ECULISHU</acronym>
  <official_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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators aim to perform the first controlled randomized prospective study using ECZ&#xD;
      in pediatric STEC-HUS. This is of great interest as there is still no efficient specific&#xD;
      therapy in that potentially devastating disease.&#xD;
&#xD;
      Furthermore, published data concerning the use of ECZ in STEC-HUS are controversial,&#xD;
      reflecting statistical bias in retrospective or uncontrolled studies, thus emphasizing the&#xD;
      need for prospective studies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hemolytic and uremic syndrome (HUS), characterized by thrombocytopenia, hemolytic anemia and&#xD;
      acute renal failure (ARF), mainly affects children younger than 5 years old. Shiga-toxin&#xD;
      (Stx) related HUS (STEC-HUS) is due to Stx secreting bacteria (mainly enterohemorrhagic&#xD;
      Escherichia Coli strains). Acute phase of STEC-HUS is severe with at least 50% of affected&#xD;
      children requiring dialysis, 20% presenting neurological involvement and 5% cardiac&#xD;
      involvement. Mortality rates can reach 5% in pediatric series and long-term renal sequels&#xD;
      have been reported in at least 30% of surviving patients. Apart from supportive care, no&#xD;
      specific treatment (such as plasma exchange) has proven its efficacy in this life-threatening&#xD;
      disease.&#xD;
&#xD;
      Recently, activation of the complement alternative pathway (CAP) has been demonstrated in&#xD;
      STEC-HUS patients and experimental studies have highlighted that Stx induce CAP activation on&#xD;
      human endothelial cells and platelet-leucocytes complexes, in addition to its direct cell&#xD;
      toxicity inducing apoptosis, both processes ending up in microvasculature thrombosis. CAP&#xD;
      activation has been demonstrated as the cause of atypical HUS (aHUS) and ECZ, a monoclonal C5&#xD;
      antibody, which inhibits the terminal complement complex (TCC) formation, can efficiently&#xD;
      prevent evolution to end stage renal disease in aHUS patients. In 2011, Lapeyraque et al.&#xD;
      reported its possible efficacy in 3 severe STEC-HUS pediatric patients. Nevertheless, in&#xD;
      STEC-HUS, ECZ has only been used in uncontrolled studies, mostly during the 2011 German&#xD;
      outbreak, with conflicting results. Considering the lack of therapy to prevent&#xD;
      life-threatening complications and renal sequels in STEC-HUS and the logically expected&#xD;
      efficacy of ECZ, controlled studies are mandatory. In recruiting centers, STEC-HUS patients&#xD;
      with ARF will be proposed to enroll the trial with the exception of patients with multiorgan.&#xD;
      After parental consent, patients will be randomized to receive either ECZ or a dextrose-based&#xD;
      placebo in a single blinded fashion. According to the patient body weight, there will be 3 to&#xD;
      5 injections at day (D) 0, D7, D14, D21 and D28. According to the length of initial hospital&#xD;
      stay, patients may have the remaining injections in the day ward of the recruiting center.&#xD;
      Dosage of ECZ will be based on previous trials using ECZ in pediatric aHUS patients. We&#xD;
      designed a single blinded study because patients treated with placebo who will develop severe&#xD;
      multiorgan involvement will be switched to the ECZ arm. ECZ or placebo will be administrated&#xD;
      intravenously as a 30-minute injection. In patients receiving hemodialysis, ECZ injection&#xD;
      will be performed after a dialysis session. Before first injection, patients will receive a&#xD;
      tetravalent meningococcal vaccine and an oral antibiotic prophylaxis to be continued up to 14&#xD;
      days after last injection.&#xD;
&#xD;
      This is a single blinded, phase III, randomized, multi-center controlled versus placebo&#xD;
      clinical trial of eculizumab in STEC-HUS patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2015</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the duration in days of extrarenal epuration</measure>
    <time_frame>From the inclusion date and assessed up to 13 months</time_frame>
    <description>Extrarenal epuration means peritoneal dialysis or hemodialysis, and is assessed at each visit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events as a measure of Safety and tolerance of treatment injections (ECZ or placebo)</measure>
    <time_frame>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)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse reactions related to the treatment (ECZ or placebo)</measure>
    <time_frame>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)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Acute Renal Failure (ARF)</measure>
    <time_frame>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)</time_frame>
    <description>Duration of ARF will be evaluated as follow : urine output measurement, creatinin clearance estimated with the Schwartz 2009 assay (based on creatinin plasma levels), ionogram, proteinuria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal sequels</measure>
    <time_frame>At 1, 6 and 12 months after last injection of ECZ (follow-up visits 7, 8, 9)</time_frame>
    <description>Renal sequels will be evaluated as follow : blood pressure, creatinin clearance, ionogram, proteinuria and microalbuminuria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematological abnormalities</measure>
    <time_frame>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)</time_frame>
    <description>Duration (in days) of the thrombocytopenia&#xD;
Duration (in days) of the hemolytic anemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood parameters of Complement Alternative Pathway (CAP)</measure>
    <time_frame>Inclusion visit (1 at day -3 to -1), Treatment visits (3, 4, 5, 6 at day 7, 14, 21, 28), follow-up visit (7 at month 2)</time_frame>
    <description>Blood parameters of CAP will be evaluated with plasmatic dosages of the complement components C3 and CD46.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibition of the Terminal Complement Complex (TCC)</measure>
    <time_frame>Inclusion visit (1 at day -3 to -1), Treatment visits (3, 4, 5, 6 at day 7, 14, 21, 28), follow-up visit (7 at month 2)</time_frame>
    <description>Inhibition of the TCC will be evaluated trough the CH50 assay and plasmatic free ECZ levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of extrarenal manifestations</measure>
    <time_frame>Inclusion Visit (1 at day -3 to -1), treatment period (visits 2, 3, 4, 5, 6 respectively at day 0, 7, 14, 21, 28)</time_frame>
    <description>Neurological involvement (seizures, coma, focal deficit)&#xD;
Cardiac involvement (cardiac failure, ischemic myocarditis, conduction or rhythm troubles)&#xD;
Digestive involvement (pancreatitis, hepatitis, hemorrhagic colitis, bowel perforation, rectal prolapsus)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>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)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Hemolytic Uremic Syndrome of Childhood</condition>
  <arm_group>
    <arm_group_label>Eculizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.&#xD;
Eculizumab (ECZ) will be administrated intravenously as a 30-minute injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.&#xD;
Placebo will be administrated intravenously as a 30-minute injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eculizumab</intervention_name>
    <description>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.&#xD;
ECZ or placebo will be administrated intravenously as a 30-minute injection</description>
    <arm_group_label>Eculizumab</arm_group_label>
    <other_name>Soloris®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>According to the patient body weight, there will be 3 to 5 injections at D0, D7, D14, D21 and D28.&#xD;
ECZ or placebo will be administrated intravenously as a 30-minute injection</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Solution with 5% glucose</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pediatric patient (1 month-18 years old)&#xD;
&#xD;
          -  Affected by STEC-HUS defined by :&#xD;
&#xD;
          -  Thrombocytopenia (&lt;150 000/mm3)&#xD;
&#xD;
          -  Mechanic hemolytic anemia (Hemoglobin &lt; 10g/dL, haptoglobin &lt;LLN, lactate&#xD;
             dehydrogenase (LDH) &gt;upper limit of normal (ULN) and/or bilirubin &gt; ULN, presence of&#xD;
             schizocytes)&#xD;
&#xD;
          -  ARF defined by an estimated Schwartz 2009 creatinin clearance &lt;75ml/min/1,73m²&#xD;
&#xD;
          -  With prodromal diarrhea and/or presence of an enterohemorrhagic strain of Escherichia&#xD;
             Coli and/or identification of the Stx 1 or 2 genes in the stool sample or rectal swab&#xD;
&#xD;
          -  Written consent of the 2 parents&#xD;
&#xD;
          -  Female patients of childbearing potential must be practicing an effective, reliable&#xD;
             and medically acceptable contraceptive regimen during the entire duration of the study&#xD;
             and 5 months after the end of the participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neonatal HUS&#xD;
&#xD;
          -  Malignancy&#xD;
&#xD;
          -  Known HIV infection&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Identified drug exposure-related HUS&#xD;
&#xD;
          -  Infection-related HUS&#xD;
&#xD;
          -  Known systemic lupus erythematosus or antiphospholipid antibody positivity or syndrome&#xD;
&#xD;
          -  Patient already enrolled in a drug trial&#xD;
&#xD;
          -  Patient with ongoing meningococcal infection&#xD;
&#xD;
          -  Patient affected by aHUS or family history of aHUS&#xD;
&#xD;
          -  STEC-HUS patient with severe multiorgan involvement at diagnostic:&#xD;
&#xD;
               -  Neurological involvement (seizures, coma, focal deficit) with signs of&#xD;
                  microangiopathy on cerebral Magnetic Resonance Imaging.&#xD;
&#xD;
               -  Cardiac involvement (cardiac failure, ischemic myocarditis, conduction or rhythm&#xD;
                  troubles)&#xD;
&#xD;
               -  Digestive involvement (severe pancreatitis defined by lipasemia&gt;500UI/L, severe&#xD;
                  hepatitis defined by transaminase &gt;x10ULN and/or prothrombin time&lt;60%,&#xD;
                  hemorrhagic colitis, bowel perforation, rectal prolapsus)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arnaud Garnier, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toulouse University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karine Brochard</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toulouse University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Amiens</city>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Angers</city>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pellegrin Hospital</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morvan Hospital</name>
      <address>
        <city>Brest</city>
        <zip>29609</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Grenoble</city>
        <zip>60107</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jeanne de Flandre Hospital</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mother and Child Hospital</name>
      <address>
        <city>Limoges</city>
        <zip>87000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women, Mother and Child Hospital</name>
      <address>
        <city>Lyon</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>La Timone Hospital</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mother and Child Hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert Debré Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trousseau Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75571</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Necker Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anne de Bretagne University Hospital</name>
      <address>
        <city>Rennes</city>
        <zip>35056</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Purpan Children Hospital</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clocheville Hospital</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>July 11, 2019</last_update_submitted>
  <last_update_submitted_qc>July 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Eculizumab</keyword>
  <keyword>Shiga-toxin</keyword>
  <keyword>hemolytic and uremic syndrome</keyword>
  <keyword>pediatric</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azotemia</mesh_term>
    <mesh_term>Hemolytic-Uremic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Hemolysis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eculizumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02205541
org study id: RC31/13/7052
secondary id: PHRC 13-0060
secondary id: 2014-001169-28
nct id: NCT02205541
lead sponsor: 
has dmc: No
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.
Hemolytic and uremic syndrome (HUS), characterized by thrombocytopenia, hemolytic anemia and
      acute renal failure (ARF), mainly affects children younger than 5 years old. Shiga-toxin
      (Stx) related HUS (STEC-HUS) is due to Stx secreting bacteria (mainly enterohemorrhagic
      Escherichia Coli strains). Acute phase of STEC-HUS is severe with at least 50% of affected
      children requiring dialysis, 20% presenting neurological involvement and 5% cardiac
      involvement. Mortality rates can reach 5% in pediatric series and long-term renal sequels
      have been reported in at least 30% of surviving patients. Apart from supportive care, no
      specific treatment (such as plasma exchange) has proven its efficacy in this life-threatening
      disease.

      Recently, activation of the complement alternative pathway (CAP) has been demonstrated in
      STEC-HUS patients and experimental studies have highlighted that Stx induce CAP activation on
      human endothelial cells and platelet-leucocytes complexes, in addition to its direct cell
      toxicity inducing apoptosis, both processes ending up in microvasculature thrombosis. CAP
      activation has been demonstrated as the cause of atypical HUS (aHUS) and ECZ, a monoclonal C5
      antibody, which inhibits the terminal complement complex (TCC) formation, can efficiently
      prevent evolution to end stage renal disease in aHUS patients. In 2011, Lapeyraque et al.
      reported its possible efficacy in 3 severe STEC-HUS pediatric patients. Nevertheless, in
      STEC-HUS, ECZ has only been used in uncontrolled studies, mostly during the 2011 German
      outbreak, with conflicting results. Considering the lack of therapy to prevent
      life-threatening complications and renal sequels in STEC-HUS and the logically expected
      efficacy of ECZ, controlled studies are mandatory. In recruiting centers, STEC-HUS patients
      with ARF will be proposed to enroll the trial with the exception of patients with multiorgan.
      After parental consent, patients will be randomized to receive either ECZ or a dextrose-based
      placebo in a single blinded fashion. According to the patient body weight, there will be 3 to
      5 injections at day (D) 0, 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. We
      designed a single blinded study because patients treated with placebo who will develop severe
      multiorgan involvement will be switched to the ECZ arm. ECZ or placebo will be administrated
      intravenously as a 30-minute injection. In patients receiving hemodialysis, ECZ injection
      will be performed after a dialysis session. Before first injection, patients will receive a
      tetravalent meningococcal vaccine and an oral antibiotic prophylaxis to be continued up to 14
      days after last injection.

      This is a single blinded, phase III, randomized, multi-center controlled versus placebo
      clinical trial of eculizumab in STEC-HUS patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: the duration in days of extrarenal epuration
time frame: From the inclusion date and assessed up to 13 months
description: Extrarenal epuration means peritoneal dialysis or hemodialysis, and is assessed at each visit.
measure: Number of adverse events as a measure of Safety and tolerance of treatment injections (ECZ or placebo)
time frame: 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)
measure: Adverse reactions related to the treatment (ECZ or placebo)
time frame: 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)
measure: Duration of Acute Renal Failure (ARF)
time frame: 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)
description: Duration of ARF will be evaluated as follow : urine output measurement, creatinin clearance estimated with the Schwartz 2009 assay (based on creatinin plasma levels), ionogram, proteinuria.
measure: Renal sequels
time frame: At 1, 6 and 12 months after last injection of ECZ (follow-up visits 7, 8, 9)
description: Renal sequels will be evaluated as follow : blood pressure, creatinin clearance, ionogram, proteinuria and microalbuminuria.
measure: Hematological abnormalities
time frame: 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)
description: Duration (in days) of the thrombocytopenia
Duration (in days) of the hemolytic anemia
measure: Blood parameters of Complement Alternative Pathway (CAP)
time frame: Inclusion visit (1 at day -3 to -1), Treatment visits (3, 4, 5, 6 at day 7, 14, 21, 28), follow-up visit (7 at month 2)
description: Blood parameters of CAP will be evaluated with plasmatic dosages of the complement components C3 and CD46.
measure: Inhibition of the Terminal Complement Complex (TCC)
time frame: Inclusion visit (1 at day -3 to -1), Treatment visits (3, 4, 5, 6 at day 7, 14, 21, 28), follow-up visit (7 at month 2)
description: Inhibition of the TCC will be evaluated trough the CH50 assay and plasmatic free ECZ levels.
measure: Incidence of extrarenal manifestations
time frame: Inclusion Visit (1 at day -3 to -1), treatment period (visits 2, 3, 4, 5, 6 respectively at day 0, 7, 14, 21, 28)
description: Neurological involvement (seizures, coma, focal deficit)
Cardiac involvement (cardiac failure, ischemic myocarditis, conduction or rhythm troubles)
Digestive involvement (pancreatitis, hepatitis, hemorrhagic colitis, bowel perforation, rectal prolapsus)
measure: Mortality
time frame: 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)
arm group label: Eculizumab
arm group type: Experimental
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: Eculizumab
description: 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
arm group label: Eculizumab
other name: Soloris®
intervention type: Drug
intervention name: Placebo
description: 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
arm group label: Placebo
other name: Solution with 5% glucose
criteria: 
gender: All
minimum age: 1 Month
maximum age: 18 Years
healthy volunteers: No
last name: Arnaud Garnier, MD
role: Principal Investigator
affiliation: Toulouse University Hospital
last name: Karine Brochard
role: Principal Investigator
affiliation: Toulouse University Hospital
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country: France
responsible party type: Sponsor
mesh term: Azotemia
mesh term: Hemolytic-Uremic Syndrome
mesh term: Syndrome
mesh term: Hemolysis
mesh term: Eculizumab