CF START 2016.

Trial name or title	The cystic fibrosis (CF) anti‐staphylococcal antibiotic prophylaxis trial (CF START); a randomised registry trial to assess the safety and efficacy of flucloxacillin as a long‐term prophylaxis agent.
Methods	Randomised controlled open trial. Parallel design. Location: multicentre (130 centres) in UK. Initial estimate of the duration of the trial: 8 years (follow‐up of each participant to 4 years of age).
Participants	Expected enrolment: 480 participants up to 70 days of age at enrolment. Expected age range: preterm newborn infants (up to gestational age < 37 weeks) n = 10; newborns (0‐27 days) n = 100; infants and toddlers (28 days‐23 months) n = 370. Diagnosis of CF through either identification of 2 CF‐causing mutations OR 1 or no CF‐ causing mutations identified and a sweat chloride test result greater than 59 mmol/L OR 2 CFTR mutations (not known CF‐causing mutations) and a sweat chloride test result greater than 29 mmol/L. Exclusion criteria: 1. An inconclusive diagnosis after newborn screening (NBS). 2. A condition (non‐CF) that, in the opinion of the recruiting investigator will impact on the long‐term management and outcome of a participant with CF. 3. Previous growth of Pseudomonas aeruginosa from respiratory culture. 4. Infants with a history of hypersensitivity to β‐lactam antibiotics (e.g. penicillins) or excipients. 5. Infants with a history of flucloxacillin associated jaundice/hepatic dysfunction.
Interventions	Intervention: 2x daily oral prophylactic flucloxacillin ("prevent and treat"). Comparator: antibiotics given in a targeted manner as per national guidelines ("detect and treat").
Outcomes	Primary outcome (assessed at all routine clinical encounters to trial completion (age, 48 months)) Age at first growth of Pseudomonas aeruginosa from respiratory culture collected as part of routine care Secondary outcomes Need for extra antibiotic treatment Number and type of respiratory culture taken during the trial period Number and proportion of respiratory cultures positive for Staphylococcus aureus Number and proportion of respiratory cultures positive for Pseudomonas aeruginosa Number and proportion of respiratory cultures positive for other significant CF pathogens Chronic airway infection Frequency of hospital admission Adverse events Nutritional status Costs to the NHS All secondary outcomes will be assessed at all encounters to trial completion (age, 48 months). Apart from determining if anti‐staphylococcal prophylaxis improves respiratory function in pre‐school children with CF which will be evaluated at trial visits between the age of 40 ‐ 48 months. As well as determining nutritional status which will be evaluated at encounters between 40 ‐ 48 months.
Starting date	16 September 2016.
Contact information	Prof Kevin Southern, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
Notes	EudraCT Number: 2016‐002578‐11.

CF: cystic fibrosis
 CFTR: cystic fibrosis transmembrane regulator
 NHS: National Health Service