Informations générales (source: ClinicalTrials.gov)
Eculizumab in Hypertensive Emergency-associated Hemolytic Uremic Syndrome: a Randomized Multicenter Controlled Trial (HYPERSHU)
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
novembre 2023
novembre 2027
29 juin 2024
Hemolytic and uremic syndrome (HUS) is a clinic-biological syndrome related to thrombotic
microangiopathy affecting predominantly the kidney. Atypical HUS (aHUS) has been
historically defined as HUS occurring in the absence of infectious event. The role of
complement dysregulation in aHUS pathophysiology has been largely demonstrated, since C
genetic rare variants are present in 60-70% aHUS patients. In line with the frequency of
C dysregulation in aHUS, Eculizumab, an anti-C5 monoclonal antibody, has dramatically
improved aHUS patients prognosis.
Numerous conditions have been associated with aHUS, including hypertensive emergency
(HE), a syndrome of acute blood pressure flare associated with end-organ damage. In cases
of HE-aHUS, whether primary aHUS is complicated by secondary HE, or primary HE leads to
secondary aHUS is still debated.
The investigators recently demonstrated that C genetic variants frequency was similar in
patients with HE-aHUS and patients with aHUS without HE, suggesting a major role for C
dysregulation in HE-aHUS. Consequently, the investigators propose to evaluate, in HE-aHUS
patients, the benefit of a strategy with early Eculizumab therapy (used within its
marketing authorization and its conditions of refunding by the health insurance in usual
care), compared to standard of care including tight blood pressure control.
The hypothesis suggests that C dysregulation may impact renal prognosis of HE-aHUS
patients. The investigator's aim to demonstrate that early Eculizumab therapy improves
prognosis of HE-aHUS patients.
Method
The HYPERSHU study is a randomized, controlled, open-labelled study including HE-aHUS
patients with severe AKI and no evidence of other conditions associated with HUS
(infections, autoimmunity, drugs, pregnancy). The investigators plan to include 62
patients. Patients will be randomized in 2 arms:
- Early Eculizumab therapy (for 3 months) added to standard of care (tight blood
pressure control).
- Standard of care alone with tight blood pressure control. Renal function after 6
months is the primary evaluation criterium.
HE is a frequently associated with aHUS, and strongly impacts patient renal prognosis.
Efficient therapeutic strategies are still lacking for this condition. The HYPERSHU study
will allow to evaluate the benefit of early Eculizumab therapy in patients with HE-aHUS
and severe renal dysfunction.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Bicêtre | EL KAROUI Khalil | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Europeen Georges Pompidou | EL KAROUI Khalil | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | EL KAROUI Khalil | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Lariboisiere-Fernand Widal | EL KAROUI Khalil | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Necker-Enfants Malades | EL KAROUI Khalil | 18/04/2025 07:55:46 | Contacter | ||
| AP-HP - Hôpital Tenon | EL KAROUI Khalil | 18/04/2025 07:55:46 | Contacter | ||
Critères
Tous
Inclusion Criteria:
- ≥ 18years
- Hospitalization for HE-aHUS within prior 10 days:
- Presume acute renal failure (renal replacement therapy or serum creatinine ≥
354µM)
- Mechanical hemolysis including: anemia, thrombopenia, and: low haptoglobin
(<LNL), or elevated LDH (>1,5UNL), or presence of schistocytes
- Severe hypertension with systolic blood pressure >180mmHg or diastolic blood
pressure>110mmHg
- 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)
- 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.
- ≥ 18years
- Hospitalization for HE-aHUS within prior 10 days:
- Presume acute renal failure (renal replacement therapy or serum creatinine ≥
354µM)
- Mechanical hemolysis including: anemia, thrombopenia, and: low haptoglobin
(<LNL), or elevated LDH (>1,5UNL), or presence of schistocytes
- Severe hypertension with systolic blood pressure >180mmHg or diastolic blood
pressure>110mmHg
- 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)
- 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.
- 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.