CF START: A national UK trial to determine whether taking an antibiotic (flucloxacillin) every day predisposes infants with cystic fibrosis (CF) to earlier infection with a bug, Pseudomonas aeruginosa, that is resistant to treatment

INTERVENTION: The randomisation sequence is generated by a computer and the infants are allocated one of two treatment strategies in a 1:1 ratio. The randomisation sequence has been generated to ensure equal allocation in clinics and centres depending on the size of those study sites. “Prevent and Treat”: Infants are prescribed oral flucloxacillin suspension of 125 mg twice a day until 36 months then 250 mg twice a day until 48 months. “Detect and Treat”: Infants prescribed antibiotics in a targeted manner for cough; asymptomatic growth of pathogens (bugs) from respiratory cultures, and as cover for a procedure requiring a general anaesthesia. Infants will receive standard CF care for four years and outcomes will be collected on the national CF Registry. The only additional (and optional) study measure will be a multiple breath washout undertaken between 40‐48 months of age. CONDITION: Specialty: Children, Primary sub‐specialty: Respiratory and cystic fibrosis; UKCRC code/ Disease: Congenital Disorders/ Congenital malformations of the respiratory system ; Genetic Diseases ; Cystic fibrosis PRIMARY OUTCOME: Age at first growth of Pseudomonas aeruginosa on a respiratory culture taken as a standard part of CF clinical care and recorded on the national CF Patient Registry SECONDARY OUTCOME: 1. Lung clearance index measured by multiple breath washout at age 40‐48 months; 2. Number of courses (and days) of extra antibiotics (oral, intravenous or aerosolised) measured on the CF registry as a routine part of CF care; 3. Number (and type) of respiratory cultures taken as a routine part of CF care during the 48 month trial period and recorded on the national CF Patient Registry (is measured using … at …); 4. Number of positive respiratory cultures for Staphylococcus aureus from samples taken as a routine part of CF care during the 48 month trial period and recorded on the national CF Patient Registry (is measured using … at …); 5. Number of positive respiratory cultures for Pseudomonas aeruginosa from samples taken as a routine part of CF care during the 48 month trial period and recorded on the national CF Patient Registry ; 6. Number of positive respiratory cultures for other significant CF pathogens from samples taken as a part of routine CF care during the 48 month trial period and recorded on the national CF Patient Registry ; 7. Chronic infection rate, as defined by “more than 50% of respiratory cultures are positive for the same pathogen during any 12 month period during the trial” during the 48 month trial period and recorded on the national CF Patient Registry ; 8. Number of inpatient stays (and number of days) during the 48 month trial period and recorded on the national CF Patient Registry ; 9. Adverse events occurring during the 48 month trial period and recorded on the national CF Patient Registry ; 10. Nutritional parameters (weight, height and weight for height percentile) are measured as a part of standard clinical care and recorded on the national CF Patient Registry during the last 8 months of the trial (age 40‐48 months); 11. CF Banding (annual cost band allocated to infants in the study each year) is measured using data from the CF Registry INCLUSION CRITERIA: 1. A confirmed diagnosis of cystic fibrosis through one of the following three routes: 1.1. Two CF‐causing mutations are identified OR 1.2. One or no CF‐ causing mutations identified and a sweat chloride test result greater than 59 mmol/L OR 1.3. Two CFTR mutations (not known CF‐causing mutations) and a sweat chloride test result greater than 29 mmol/L 2. Age 70 days or less 3. Consent for inclusion on the national UK CF Registry 4. Consent for inclusion in the CF START trial