Adult patients with aHUS associated with HE and severe kidney involvement (needing dialysis or serum creatinine = 354µM). MedDRA version: 20.1 Level: PT Classification code 10079840 Term: Atypical haemolytic uraemic syndrome System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Soliris 300 mg solution à diluer pour perfusion
Product Name: ECULIZUMAB
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Eculizumab
CAS Number: 219685-50-4
Sponsors
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - Hospitalization forHE-aHUS within prior 10 days: o Presume acute renal failure (renal replacement therapy or serum creatinine = 354µM). o Mechanical hemolysis including: anemia, thrombopenia, and: low haptoglobin (1,5UNL), or presence of schistocytes o Severe hypertension with systolic blood pressure >180mmHg and/or diastolic blood pressure>110mmHg o Target organ damage, including neurological involvement (notably hypertensive encephalopathy, headache, confusion, nausea, posterior reversible encephalopathy syndrome), or cardiovascular involvement (notably acute left ventricular failure, acute pulmonary edema, acute cardiac ischemia, chest pain, dyspnea, palpitations), or ophtalmological involvement (notably ischemic retinopathy or blurred vision) - For women of childbearing potential: Effective contraception during the study and for at least 5 months after the last dose of treatment with eculizumab - Subject affiliated to a social security regimen - Subject having signed written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 53 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: - Atrophic kidneys with maximum length<8cm on recent (<1 month) renal ultrasound, CT scan, or renal MRI - High clinical suspicion of Complement-mediated aHUS (including familial history of aHUS) - High clinical suspicion of typical HUS (including Shiga Toxin-producing E. Coli infection) or Thrombotic thrombocytopenic purpura - High clinical suspicion of secondary HUS related to autoimmune disease (including lupus, scleroderma, antiphospholipid syndrome, ANCA vasculitis), or C3 glomerulopathy. - High clinical suspicion of recent hemorrhagic or ischemic stroke. - ADAMTS 13<10%, HIV or HCV infection, positivity of 2 markers among: anticardiolipin IgG/antiBeta2 GP1 IgG/lupus anticoagulant, positivity of ANCA (ELISA PR3 or MPO) - Active infection - Subjects with unresolved Neisseria meningitidis infection - Subjects refusing Neisseria meningitidis vaccination or refusing antibioprophylaxis with oracillin (In case of penicillin allergy, antibioprophylaxis with macrolide couldbeproposed according to ANSM recommendations (azithromycin or roxithromycin)). - Contra-indication to eculizumab or renin angiotensin system blockers - Solid organ or haematopoietic transplant - History (<1year) of active cancer or exposition to drugs associated with aHUS (< 3 months) - Severe cognitive or psychiatric disorders, patients unable to give an informed consent. - PCR SARS-CoV2 positive - Pregnant or breastfeeding woman or ineffective contraception - Persons deprived of their liberty by judicial or administrative decision, - Persons under legal protection (guardianship, curatorship) - Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of early Eculizumab administration added on standard of care BP control on dialysis-dependence at month 6 in HE-aHUS patients with severely impaired initial renal function.;Secondary Objective: To evaluate the role of complement biomarkers in predicting therapeutic response To evaluate the frequency of complement genetic rare variants in this population To evaluate the efficacy of early eculizumab administration added on standard of care BP control on 3-month (W13) and 12 months renal replacement therapy risk To evaluate the frequency of severe infections in both groups To evaluate the time to resolution of hemolysis and acute dialysis To evaluate the frequency of histological lesions and their prognosis (if kidney biopsy is performed) To evaluate the medico-economic impact of Eculizumab. Objective of any potential ancillary study: biological collection To identify new genetic variants related to HE-aHUS. This part of the project will have a complementary funding ;Primary end point(s): 6-month response to therapy, as defined by the absence of any of the following events: i) lack of renal efficacy at 6-month follow-up: persistent renal replacement therapy, eGFR <15ml/mn/1,73m2, or patient death; ii) lack of early hemolysis control: persistent hemolysis at W2 despite well conducted antihypertensive therapy leading to Eculizumab conversion [control group].;Timepoint(s) of evaluation of this end point: at 6 Month. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Prognosis role of repeat complement biomarkers (W1, W4, W13) - Frequency of Complement genetic rare variants - Renal replacement therapy rates at months 3 and 12 follow-up - Frequency of severe infections (defined by the need for hospitalization) - Time to resolution of haemolysis - Time to resolution of renal replacement therapy - Frequency and prognostic role of kidney lesions (glomerular and arteriolar microthromboses), glomerulosclerosis and kidney fibrosis if kidney biopsy is performed - Costs relating to renal replacement therapy (or lack of), Eculizumab and other antihypertensive treatments, hospitalizations.;Timepoint(s) of evaluation of this end point: at 3 month and 12 month. | — |
Countries
France
Contacts
Public ContactMyriem
AP-HP
Outcome results
None listed