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

The Neonatal Unit at UHW are currently participating in the ‘Optimist-A Trial’ and I thought this would be the perfect platform to raise awareness and explain briefly about the trial…
 
What is it?
An international multicentre randomised controlled trial of surfactant administration whilst on CPAP, in preterm infants 25-28/40 gestation.
 
Research Question
Does administration of exogenous surfactant using a minimally-invasive technique improve outcome in preterm infants treated with continuous positive airway pressure (CPAP)?
 
Why is it important?
Premature babies ( ≤28 weeks gestation) with significant surfactant deficiency on CPAP have historically required intubation for the administration of surfactant therapy, with subsequent increased associated risk of death, bronchopulmonary dysplasia (BPD) and other morbidities.
In an attempt to address this problem, minimally-invasive surfactant therapy (MIST) techniques have been developed whereby exogenous surfactant is administered via an instillation catheter, inserted briefly into the trachea under direct laryngoscopy, whilst on CPAP.
 
Eligibility Criteria

• Inborn preterm infants 25-28/40 gestation
• Age < 6 hours
• On CPAP due to RDS
• FiO2 ≥ 0.30

 
Randomisation
Eligible infants will be randomly allocated to receive exogenous surfactant via MIST, or continue on CPAP.
 
Intervention

• Curosurf administration (200mg/kg) via brief tracheal catheterisation under direct visualisation, followed by recommencement of CPAP.
• Controls continue on CPAP
• Intervention is masked from the clinical team

Primary Outcome

• Death or BPD at 36/40 corrected gestation

Secondary Outcomes

• Incidence of major neonatal morbidities (intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotising enterocolitis)
• Pneumothorax and patent ductus arteriosus
• Need for intubation and surfactant therapy
• Durations of mechanical respiratory support, intubation, CPAP, intubation and CPAP, high flow nasal cannula (HFNC), oxygen therapy, intensive care stay and hospitalisation
• Hospitalisation cost
• Applicability and safety of the MIST procedure
• Outcome at 2 years

 
Any further queries?
Contact Rachel Hayward Neonatal SpR at UHW, for any further information (Rachel.hayward@doctor.org.uk)