Hemolytic Uremic Syndrome of Childhood Clinical Trial
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
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.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT03690024 -
Outcame of Cases With Hemolytic Uremic Syndrome Attending Assiut University Child Hospital
|