Eculizumab in Hypertensive Emergency-associated Hemolytic Uremic Syndrome
Status:
Not yet recruiting
Trial end date:
2026-04-01
Target enrollment:
Participant gender:
Summary
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.