Acute Lymphoblastic Leukaemia - Category
Conditions
Keywords
antibiotic prophylaxis
Brief summary
CiproPAL is a randomised trial comparing daily ciprofloxacin with local standard care during the induction phase of paediatric ALL treatment, and aims: 1. To assess the efficacy of ciprofloxacin prophylaxis in the reduction of infection during the induction phase of treatment for paediatric Acute Lymphoblastic Leukaemia within the ALLTogether-1 Trial. 2. To evaluate the impact of ciprofloxacin prophylaxis on antimicrobial resistance, both of invasive infections and colonising organisms.
Detailed description
This is a multi-centre randomised trial of prophylactic ciprofloxacin (10mg/kg BD, enteral/IV) versus standard of care during the neutropenic period of induction (with an internal pilot study) in patients aged 1-17 years with de-novo ALL treated on ALLTogether-1. Exclusion criteria include: patients with Down syndrome (who already receive ciprofloxacin prophylaxis), contraindication to fluoroquinolones, non-consent to ALLTogether-1 or CiproPAL. AMR of colonising organisms will be assessed with stool or peri-rectal swab cultures performed at five timepoints within the first year. Longer term invasive infection AMR monitoring will include sensitivity testing of all organisms isolated in confirmed infection for the duration of ALLTogether-1. The primary outcome is the rate of sterile site bacterial infections during induction, evaluated by intention to treat analysis. Secondary outcomes include rates of febrile episodes, febrile neutropenia, severe infection and infection-related death; rates of AMR; antibiotic exposure; secondary infections; and quinolone side effects. A model-based health economic analysis will be undertaken. Using a conservative effect estimate of 40% reduction in bacteraemia (i.e. a reduction from 15% to 9%) 1052 patients randomised 1:1 gives 85% power with a 5% 2-sided alpha.
Interventions
DRUGCiprofloxacin
prophylactic ciprofloxacin (10mg/kg BD, enteral/IV)
DRUGAntibiotic
Standard of care antibiotic as per local policy
Sponsors
University College, London
National Institute for Health Research, United Kingdom
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Randomised trial of prophylactic ciprofloxacin (10mg/kg BD, enteral/IV) versus standard of care during the neutropenic period of induction (with an internal pilot study) in patients aged 1-17 years with de-novo ALL treated on ALLTogether-1. Exclusion
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Paediatric patients (1-17 years inclusive) with de-novo Acute Lymphoblastic Leukaemia treated on ALLTogether-1 in the UK in the first 5 days of therapy, up to 14 days is acceptable. * Written informed consent
Exclusion criteria
* Non-participants of the ALLTogether-1 trial * Patients with Down syndrome who already receive ciprofloxacin prophylaxis * Chronic active arthritis * Other contraindication to fluoroquinolones
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| rate of sterile site bacterial infections during induction | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | rate of sterile site bacterial infections during induction |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| rates of febrile episodes | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | rates of febrile episodes |
| rates of febrile neutropenia | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | rates of febrile neutropenia |
| rates of severe infection and infection-related death | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | severe infection rates and deaths from infection |
| rates of AMR (antimicrobial resistance) | Until the end of trial approx 10 years (from randomisation until the end of trial declaration in 2031) | rates of AMR |
| rates of antibiotic exposure | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | rates of antibiotic exposure |
| rates of secondary infections | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | rates of secondary infections |
| quinolone side effects | during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction) | quinolone side effects |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORRobert Phillips
University of York
Outcome results
None listed