Shiga-toxin producing Escherichia coli Haemolytic Uraemic Syndrome (STEC HUS) Infections and Infestations
Conditions
Interventions
Prior to entering the trial, all potential patients will commence an 8 week course of antibiotics (either phenoxymethylpenicillin or erythromycin if allergic to penicillin). Once they have been entere
one dose soon after arriving at the children’s kidney unit (day 1), and a second dose of the same medicine a week later (day 8).
Participants will be randomised to either of the follo
Sponsors
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Children aged 6 months to <19 years 2. Weight of =5kg 3. A diagnosis of HUS: 3.1. Micro-angiopathic haemolytic anaemia (indicated by fragmented red cells on blood film or plasma lactate dehydrogenase above local centre reference range) 3.2. AND Thrombocytopenia (platelets <150x109/l) 3.3. AND AKI of “injury” or "failure" category of pRIFLE criteria (despite correction of hypovolaemia) 4. Reported diarrhoea within 14 days prior to diagnosis of HUS (defined according to World Health Organisation as "the passage of three or more loose or liquid stools per day - or more frequent passage than is normal for the individual") OR A stool culture/shiga toxin PCR/STEC result indicating STEC in the patient or household contact within 14 days prior to diagnosis of HUS. Patient intended to be able to receive trial drug within 36 hours of arrival at renal unit, or within 24 hours of eligibility if already at renal unit 5. Patient intended to be able to receive trial drug within 36 hours of arrival at the renal unit, or within 24 hours of eligibility if already at renal unit 6. Sexually active male or female patients must agree to practice an effective, reliable and medically approved contraceptive regimen for 6 months after enrollment 7. Written informed consent obtained from the participant’s parents/guardians and written assent obtained from participant (where age appropriate). Participants aged 16 years and above will provide their own written informed consent
Exclusion criteria
Exclusion criteria: 1. Family history of atypical HUS (aHUS) 2. Previous episode of HUS 3. Known pre-existing eGFR < 90ml/min / 1.73m2 4. Known or suspected pneumococcal infection 5. Known or suspected meningococcal infection 6. Patient taking a drug known to be associated with HUS, e.g. calcineurin inhibitors, chemotherapy, quinine, oral contracaptive pill 7. Hypersensitivity to eculizumab, murine proteins or any of the excipients listed in the Summary of Product Characteristics 8. Pregnancy or lactation 9. Malignancy 10. Known Disseminated Intravascular Coagulopathy (testing of coagulation is not mandatory for inclusion in trial) 11. Refusal of consent, including consent for meningococcal vaccination or antibiotic prophylaxis 12. Currently participating in another CTIMP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Severity of acute kidney injury and extra-renal events is assessed using the purpose-developed STEC HUS clinical severity score at day 60. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival is measured by survival status at 52 weeks 2. Duration of dialysis, measured by the number of days on dialysis over 52 weeks 3. Duration of thrombocytopenia, measured by the number of consecutive days until platelet count >150x109/l up until 52 weeks. Participants enter the trial with a platelet count 2.5mg/mmol on early morning urine] or eGFR<90ml/min/1.73m2 at 52 weeks) collected at week 52 only 8. eGFR measured using a centralised cystatin C assay at 52 weeks collected at baseline, discharge, day 30, day 60, week 26 and week 52 9. Persistent neurological defect rate, measured by a structured expert assessment to include CNS examination, vision, hearing and neuropsychological assessment measured at 60 days based on the CRFs we measure this at baseline, discharge, day 30 and day 60 10. Economic evaluation of cost per clinical severity score point measured at day 60, and cost per QALY gained, measured by PedsQL and CHU-9D assessments which are collected at baseline, day 8, day 30, day 60, week 26 and week 52 | — |
Countries
England, United Kingdom
Contacts
Public ContactHugh;Raquel Jarrett;Fernández del Río
;
Outcome results
None listed