Clinical trial NCT04678869: CiproPAL (Ciprofloxacin Prophylaxis in Acute Leukaemia)
Official title: CiproPAL (Ciprofloxacin Prophylaxis in Acute Leukaemia): A Randomised Trial to Assess the Use of Ciprofloxacin Prophylaxis to Prevent Bacterial Infection in Children Treated on the Induction Phase of the ALLTogether-1 Treatment Protocol
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Lymphoblastic Leukaemia - Category
Keywords: antibiotic prophylaxis
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2020-12-22
Enrollment: 1052
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: rate of sterile site bacterial infections during induction
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
Secondary outcomes:
measure: rates of febrile episodes
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
measure: rates of febrile neutropenia
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
measure: rates of severe infection and infection-related death
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
measure: rates of AMR (antimicrobial resistance)
timeFrame: Until the end of trial approx 10 years (from randomisation until the end of trial declaration in 2031)
measure: rates of antibiotic exposure
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
measure: rates of secondary infections
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
measure: quinolone side effects
timeFrame: during induction approx 1 month (from randomisation until the start of consolidation, discontinuing protocol antileukaemic therapy or death post induction)
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: London
country: United Kingdom
facility: Univeristy College Hospital London
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham Children's Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: University of York
name: Robert Phillips
role: PRINCIPAL_INVESTIGATOR
References: