ECUSTEC

‘Eculizumab in Shiga-Toxin producing E. Coli Haemolytic Uraemic Syndrome: A Randomised, Double-Blind, Placebo-Controlled Trial’

This is a trial currently recruiting on the Paediatric Nephrology Unit at UHW

Aim of trial:
To assess whether Eculizumab reduces the severity of Shiga-toxin producing Ecoli Haemolytic Uraemic Syndrome (STEC HUS) in children and young people
 
Background:

• HUS - Commonest cause of intrinsic acute kidney injury in children
• Classical triad: Microangiopathic haemolytic anaemia, thrombocytopenia, acute kidney injury
• 95% of HUS cases occur post infection with Shiga-toxin producing E. coli (STEC) – ‘Typical’ HUS
• ~ 120 cases/year in UK
• 2-3% mortality rate, 50-60% of children require dialysis
• Long term complications in ~30% of survivors e.g. CKD, permanent brain injury  

 
 
What is Eculizumab?

• A monoclonal antibody that inhibits complement
• Incredibly expensive
• Already in use for the treatment of Atypical HUS
• Previous studies into the use of Eculizumab in STEC-HUS have generated variable findings, with no objective evidence of efficacy or safety in children.  There has been no prospective, controlled trial in STEC-HUS

 
 
Primary Research Objective:
To determine whether the severity of STEC HUS is less in those given Ecu compared with those given placebo, in children aged 6m-18 years
​
-Clinical Severity Score assigned at day 60
 
Secondary Objectives:
i)To assess the safety of Ecu in STEC HUS
ii)To determine whether the incidence of CKD following STEC HUS is less in those receiving Ecu compared with those receiving placebo
iii)To evaluate the cost-effectiveness of administration of Ecu in STEC HUS from the perspective of the NHS
 
 
 
Inclusion Criteria

• Age 6m to <19y
• Weight ≥5kg
• Diagnosis of HUS

                                                  - MAHA
                                                  - Thrombocytopaenia
                                                  - AKI​

• EITHER Reported Diarrhoea within 14d prior to diagnosis​ OR stool culture/shiga toxin PCR/STEC serology result indicating STEC in the patient or household contact within 14 days prior to diagnosis of HUS
• Patient to receive Eculizumab within 36hours of arrival to renal unit

 
Exclusion Criteria

• Family history of aHUS
• Previous episode of HUS
• Known pre-existing eGFR <90ml/min/1.73m2
• Known/suspected pneumococcal infection or meningococcal infection
• Patient taking a drug known to be a/w HUS
• Pregnancy
• Malignancy

 
 
 
Active arm: Standard therapy + 1st dose Ecu Day 1, & 2nd dose Ecu Day 8
 
Control arm: Standard therapy + 1st dose placebo Day 1, & 2nd dose placebo Day 8

NB:  The trial contains an internal pilot phase of 18m (12m recruitment, 6m follow-up), the purpose of which is to determine whether the substantive trial will continue.

For further information please contact:
​ Jennifer Muller, Paediatric Research Specialist Nurse (CYARU)
Jennifer.muller@wales.nhs.uk

Annabel Greenwood
Paediatric ST3