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PERUKI research studies currently enrolling

Anaphylaxis registry 

Food allergy is the most common cause of potentially life-threatening, anaphylaxis reactions in children and young people. There is an urgent need to learn more about the circumstances of allergic reactions in the community, to reduce the risk to individuals from anaphylaxis. However, existing NHS data does not provide sufficient information as to the cause and circumstances of reactions. The UK Anaphylaxis Registry provides a platform for clinicians to record details of all significant allergic reactions - irrespective of trigger - presenting to Emergency Departments in the UK, to help address this evidence gap. Understanding more about circumstances of allergic reactions occurring in the community will help us better inform patient care and guide public policy, for example with respect to allergen labelling. More details here or email anaphylaxis.registry@imperial.ac.uk

CRAFFT

The UK is more interventional than many countries, including the USA, in the treatment of distal radius fractures in children. Standard UK treatment is surgical correction, whilst others often follow a non-operative approach. There is low quality evidence that these fractures heal well and completely correct themselves without surgery in children under 11 years old, even if bones are initially displaced. There is a clear and pressing need to inform patients about benefits or otherwise of treatment options, and a need to inform commissioners regarding the costs to the NHS and society. CRAFFT (The Children’s Radius Acute Fracture Fixation Trial) is a multi-centre prospective randomized non-inferiority trial of surgical reduction versus non-surgical casting for severely displaced off-ended distal radius fractures (metaphyseal or Salter Harris) in children aged 4 to 10 years. In this cross-network (PERUKI & BSCOS) study the primary outcome is the Patient Reported Outcomes Measurement Information System Upper Extremity Score for Children (PROMIS UE). The trial started in 2019 and recruitment will finish in 2023. The sample size is 750 children. More details here

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CRESCENT

Convulsive status epileptics (CSE) is the commonest neurological emergency seen in paediatric emergency departments and an important cause of preventable neurological disability and death. A large body of preclinical evidence suggests that pH is an important factor in both seizure onset and seizure termination, with the former occurring under alkaline and the latter under acidic conditions. CRESCENT is a trial evaluating the safety and efficacy of a potential new contribution to the management of status, using modest pH manipulation (achieved by substituting 100% high flow oxygen with a mixture of 95% oxygen 5% CO2, supplied in small, overpainted, CD size cylinders) to induce mild acidosis alongside standard medical (APLS) management to see if this increases the success rate of first line treatment. 

 

CRESCENT builds on the ECLiPSE trial run so successfully by PERUKI several years ago using a similar, but simplified, design; again with a deferred consent approach. No randomisation is required at the time of treatment, and no additional samples, procedures or outcome assessments are required. 

 

The trial opened in Summer 2023 with eight PERUKI sites open currently with four additional sites being opened. An interim analysis after 50% enrolment (provisionally late 2024) will determine whether the study continues.

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CURLY

This trial aims to determine the optimal duration of oral cefalexin treatment for infants and young children with a clinical diagnosis of febrile urinary tract infection (UTI). There is limited evidence for the optimal duration, and widespread variation in practice. 

Design: A multi-centre, open label, multi-arm randomised controlled trial using a “DURATIONS design”, which will produce a “cefalexin duration vs cure rate” curve in order to determine the optimal number of treatment days.

Setting: 10 Paediatric emergency departments (EDs) across the UK from within Paediatric Research in the UK and Ireland (PERUKI).

Target population: Infants and children with a clinical diagnosis of febrile UTI in whom the decision has been made to treat with oral cefalexin.

Intervention: Patients will be randomised to one of 5 cefalexin course durations (3, 5, 6, 8 or 10 days). 

Randomisation: Patients will be allocated to groups using central randomisation in a 1:1:1:1:1 ratio with minimisation to ensure balance for age group, sex and study site.

Primary outcome: Clinical UTI cure, defined as patients in whom there is (i) fever resolution and (ii) no additional systemic antibiotic prescription by 16 days post-randomisation. 

For more information contact curly@trials.bham.ac.uk 

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EAS

Infants under 90 days of age are at higher risk of serious bacterial infections (SBI) when compared to older children. The most common SBI in this cohort is a urinary tract infection (UTI). In the UK the National Institute for Health and Care Excellence (NICE) recommends that all febrile infants under three months of age with abnormal urinalysis should receive parenteral antibiotics pending urine culture results. Internationally practices vary and a group of “low risk” infants have been identified as suitable for management in the community with oral antibiotics.

Design: A multi-centre, open label, randomised controlled trial comparing parenteral and oral antibiotics for the management of suspected UTI in “low risk” infants.

Setting: Paediatric emergency departments (EDs) across the UK, from within the Paediatric Research in the UK and Ireland (PERUKI) research network.

Target population: Well appearing infants aged 29-90 days inclusive with a history of fever, a C-reactive protein (CRP) level <20mg/l, an absolute neutrophil count (AND) <5,200/mm3 and an abnormal urinalysis.

Intervention: Patients will be randomised to either parenteral antibiotics or oral antibiotics pending urine culture results.

Randomisation: Patients will be allocated in a 1:1 ratio.

Outcomes: Additional parenteral antibiotics within 7 days of randomisation. Secondary outcomes include; treatment failure within 7 and 28 days of randomisation, time to defervescence, time to normal feeding, time to normal activity, length of stay, antibiotic-associated adverse events, adherence to trial drug, paediatric quality of life (measured using PedsQL acute infant version), family impact (measured using PedsQL Family Impact Module acute version), health service use and costs.

Follow-up: To 28 days (+/- 2 days) post-randomisation.

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Breathing Assistance in CHildren with bronchiolitis (BACHb): a group-sequential two-stratum multicentre open-label randomised clinical trial of respiratory support in infants with acute bronchiolitis

The role of high-flow nasal cannula (HFNC) in the management of hospitalised infants with moderate and severe bronchiolitis is unclear. RESEARCH QUESTIONS 1) In hospitalised infants with bronchiolitis not responding to low-flow nasal cannula oxygen (moderate bronchiolitis) [Population], is the use of HFNC [Intervention] superior to humidified standard oxygen (HSO) [Comparator] in reducing time to hospital discharge [Outcome]? 2) In hospitalised infants with bronchiolitis and severe respiratory distress (severe bronchiolitis) [Population], is the use of HFNC [Intervention] superior to nasal continuous positive airway pressure (CPAP) [Comparator] in reducing time to hospital discharge [Outcome]? METHODS DESIGN: Four-stage group-sequential design, two-stratum, multicentre, open-label, randomised clinical trial, with 6-month internal pilot phase and integrated health economic evaluation. SETTING: Emergency departments, assessment units and paediatric wards in 50 UK National Health Service (NHS) hospitals. INCLUSION CRITERIA: Hospitalised infant aged <12 months with a clinical diagnosis of acute bronchiolitis and clinically assessed at least twice 15 minutes apart to have EITHER: (A) Severe respiratory distress and/or recurrent short apnoeas [Severe stratum], OR (B) Lack of response to low-flow oxygen =2 L/min, with persistent hypoxia and/or moderate respiratory distress [Moderate stratum]. EXCLUSION CRITERIA: (1) Clinical decision that patient needs immediate intubation and ventilation; (2) Ongoing active air leak; (3) Received HSO, HFNC or CPAP for >2 hours in prior 24 hours; (4) On home ventilation; (5) Tracheostomy in place; (6) Nasal/midfacial anomalies or recent craniofacial surgery; (7) Previously recruited to BACHb trial. HEALTH TECHNOLOGIES: Severe stratum: HFNC at a flow rate of 2 L/kg/minute compared with nasal CPAP at a set expiratory pressure of 6-8 cm H2O. Moderate stratum: HFNC at a flow rate of 2 L/kg/minute compared with HSO up to 15 L/minute. CONSENT: Due to the emergency nature of the treatment, based on PPI feedback, we will defer written informed consent to after randomisation. Brief study information leaflets and posters will be available. All treatments are already used in clinical practice. PRIMARY OUTCOME: Time from randomisation to hospital discharge. SECONDARY OUTCOMES: Treatment failure; mortality; intubation and invasive ventilation; intensive care unit admission; sedation use; duration of oxygen therapy; time to adequate (75%) oral feeding; patient comfort; hospital readmission within 30 days; and health status at 30 and 90 days. Cost-effectiveness expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. SAMPLE SIZE: Severe stratum: A total of 584 patients (HFNC: 292, CPAP: 292) is necessary to detect a 25% decrease in median time to hospital discharge in HFNC group (HR=1.33). Moderate stratum: A total of 924 patients (HFNC: 462, HSO: 462) is necessary to detect a 20% decrease in median time to discharge in HFNC group (HR=1.25). Both provide 90% power at 5% two-sided level of significance. TIMELINE: Total duration 42 months (HRA/site approvals 1-11; patient recruitment 6-35; internal pilot 6-11; follow-up 7-38; analysis/dissemination: 36-42). IMPACT/DISSEMINATION: BACHb is the largest clinical trial in bronchiolitis and will inform national/international guidelines. Findings will be disseminated widely through the medical and lay press, study website and social media.

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PICBONE

This study aims to understand how helpful ultrasound and MRI scans are in diagnosing bone and joint infections in children. In addition, PICBONE will create a pathway that clinicians can use in the Emergency Department to more successfully diagnose bone and joint infections. 

 

Design: A multi-centre, observational study with two components

1. Retrospective data collection on patients with potential bone and joint infection.  These data will be used to derive a clinical pathway

2. Prospective arm, with data collection and consent for follow-up at 3 months. This will test how well this pathway works on a new group of children with suspected infections

Further information is available via picbone@ndorms.ox.ac.uk

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