ECULIZUMAB for Atypical haemolytic uraemic syndrome | Hypertensive emergency

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years\n- Hospitalization forHE-aHUS within prior 10 days: o Presume acute renal failure (renal replacement therapy or serum creatinine ≥ 354μM). o Mechanical hemolysis including: anemia, and: thrombopenia, or low haptoglobin (1,5UNL), or presence of schistocytes or histological lesions of thrombotic microangiopathy 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)\n- For women of childbearing potential: Effective contraception during the study and for at least 5 months after the last dose of treatment with eculizumab\n- Subject affiliated to a social security regimen\n- Subject having signed written informed consent"}

Exclusion criteria

• {"criterion_text":"- Atrophic kidneys with maximum length<8cm on recent (<1 month) renal ultrasound, CT scan, or renal MRI\n- Contra-indication to eculizumab or renin angiotensin system blockers\n- Solid organ or haematopoietic transplant\n- History (<1year) of active cancer or exposition to drugs associated with aHUS (< 3 months)\n- Severe cognitive or psychiatric disorders, patients unable to give an informed consent\n- Positive SARS-CoV2 PCR or antigenic test\n- Pregnant or breastfeeding woman or ineffective contraception\n- Persons deprived of their liberty by judicial or administrative decision\n- Persons under legal protection (guardianship, curatorship)\n- Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants\n- High clinical suspicion of Complement-mediated aHUS (including familial history of aHUS)\n- High clinical suspicion of typical HUS (including Shiga Toxin-producing E. Coli infection) or Thrombotic thrombocytopenic purpura\n- High clinical suspicion of secondary HUS related to autoimmune disease (including lupus, scleroderma, antiphospholipid syndrome, ANCA vasculitis), or C3 glomerulopathy.\n- High clinical suspicion of recent constituted hemorrhagic or ischemic stroke justifying specific blood pressure targets\n- 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)\n- Active infection\n- Subjects with unresolved Neisseria meningitidis infection\n- 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))"}

Primary endpoints

• {"endpoint_text":"- Response to therapy, defined by the absence of any of the following events: i) at 6-month follow-up: persistent renal replacement therapy, eGFR<15ml/mn/1,73m2, or patient death; ii) at W2 : persistent hemolysis despite well conducted antihypertensive therapy. Any Eculizumab rescue in the control group will be considered as a failure.","definition_or_measurement_approach":"Primary endpoint defined as absence of specified events: at 6 months persistent renal replacement therapy, eGFR < 15 ml/min/1.73m2, or death; at week 2 persistent hemolysis despite well conducted antihypertensive therapy. Eculizumab rescue in control group counted as failure."}

Secondary endpoints

• {"endpoint_text":"- Prognosis role of repeat complement biomarkers (W1, W4, W13)","definition_or_measurement_approach":"Repeated complement biomarker measurements at week 1, week 4, and week 13 to assess prognostic value."}
• {"endpoint_text":"- Frequency of Complement genetic rare variants","definition_or_measurement_approach":"Assessment of frequency of rare complement genetic variants in study population (genetic testing)."}
• {"endpoint_text":"- Renal replacement therapy rates at months 3 and 12 follow-up","definition_or_measurement_approach":"Rates of renal replacement therapy measured at month 3 and month 12 follow-up."}
• {"endpoint_text":"- Frequency of severe infections (defined by the need for hospitalization)","definition_or_measurement_approach":"Severe infections defined by events requiring hospitalization; frequency compared between groups."}
• {"endpoint_text":"- Time to resolution of haemolysis","definition_or_measurement_approach":"Time-to-event measurement: time from randomisation to documented resolution of haemolysis."}
• {"endpoint_text":"- Time to resolution of renal replacement therapy","definition_or_measurement_approach":"Time-to-event measurement: time from randomisation to cessation/resolution of renal replacement therapy."}
• {"endpoint_text":"- Frequency and prognostic role of kidney lesions (glomerular and arteriolar microthromboses), glomerulosclerosis and kidney fibrosis if kidney biopsy is performed","definition_or_measurement_approach":"If kidney biopsy performed, histological assessment of lesions and analysis of their frequency and prognostic role."}
• {"endpoint_text":"- Costs relating to renal replacement therapy (or lack of), Eculizumab and other antihypertensive treatments, hospitalizations","definition_or_measurement_approach":"Health economic assessment of costs associated with renal replacement therapy, eculizumab, antihypertensive treatments, and hospitalizations."}

France

Earliest CTIS Part Ii Submission Date

30-10-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

495

Number Of Sites

16

Number Of Participants

66

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"DGOS - French Ministry of Health","duties_or_roles":"Source of monetary support","organisation_type":""}