A trial to determine the safest and most effective antibiotic strategy for infants diagnosed with CF.

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2016-002578-11-GB
• Date of registration: 09/08/2016
• Prospective Registration: Yes
• Primary sponsor: Alder Hey Children's NHS Foundation Trust
• Public title: A trial to determine the safest and most effective antibiotic strategy for infants diagnosed with CF.
• Scientific 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 longterm prophylaxis agent for infants with CF. - CF START
• Date of first enrolment: 16/09/2016
• Target sample size: 480
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002578-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Antibiotics given in a targeted manner as per national guidelines Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Abigail Bennett
• Affiliation: MC- CTU

• Name: Abigail Bennett
• Affiliation: MC- CTU

Key inclusion & exclusion criteria

Inclusion criteria:
1. A confirmed diagnosis of cystic fibrosis through one of the following three routes:
- Two CF-causing mutations are identified.
OR
- One or no CF- causing mutations identified and a sweat chloride test result greater than 59 mmol/L.
OR
- 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 480
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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 PsA from respiratory culture.
4. Infants with a history of hypersensitivity to ß-lactam antibiotics (e.g. penicillins) or excipients
5. Infants with a history of flucloxacillin associated jaundice/hepatic dysfunction.

*Infants with an inconclusive diagnosis after NBS (termed ‘CF Screen Positive Inconclusive Diagnosis (CFSPID)’) should not receive standard CF care and should not be recruited into CF START (Munck et al 2015).
The two situations that result in a diagnosis of CFSPID after NBS are;
• Two CFTR mutations recognised, one or both of which are not characterised as CF-causing and the sweat chloride is less than 30 mmol/L
• The sweat chloride is repeatedly between 30-59 mmol/L and only one or no CFTR mutations are recognised

**Significant non-CF conditions might include chromosomal abnormality (for example, Down syndrome), cerebral palsy, chronic lung disease (oxygen requirement) following pre-term birth and other significant congenital anomalies (for example, severe cardiac disease, tracheo-oesophageal fistula, diaphragmatic hernia).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Cystic fibrosis
MedDRA version: 19.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Flucloxacillin 250mg/5ml Sugar-Free Powder for Oral Solution
Product Name: Flucloxacillin
Product Code: na
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: Flucloxacillin
CAS Number: 5250-39-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 25-50-mg/ml

Primary Outcome(s)

Main Objective: To demonstrate that infants on anti-staphylococcal antibiotic prophylaxis (“Prevent and Treat”) are not predisposed to earlier airway infection with Pseudomonas aeruginosa.

Primary end point(s): Age at first growth of Pseudomonas aeruginosa from respiratory culture collected as part of routine care

Timepoint(s) of evaluation of this end point: All routine clinical encounters to trial completion (age, 48 months)

Secondary Objective: - To determine if anti-staphylococcal antibiotic prophylaxis (ASAP) improves respiratory function in pre-school children with CF
- To determine the need for extra antibiotic treatment
- To determine the number and type of respiratory culture taken during the trial period
- To determine the number and proportion of respiratory cultures positive for Staphylococcus aureus (SA)
- To determine the number and proportion of respiratory cultures positive for Pseudomonas aeruginosa (PsA)
- To determine the number and proportion of respiratory cultures positive for other significant CF pathogens
- To determine if there is evidence of chronic airway infection
- To determine the frequency of hospital admission
- To identify any adverse events
- To determine nutritional status
- To determine the costs to the NHS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: All secondary endpoints detailed above will be recorded at all encounters to trial completion (age, 48 months). Apart from determining if ASAP 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.

Secondary end point(s): To determine the need for extra antibiotic treatment
To determine the number and type of respiratory culture taken during the trial period
To determine the number and proportion of respiratory cultures positive for Staphylococcus aureus (SA)
To determine the number and proportion of respiratory cultures positive for Pseudomonas aeruginosa (PsA)
To determine the number and proportion of respiratory cultures positive for other significant CF pathogens
To determine if there is evidence of chronic airway infection
To determine the frequency of hospital admission
To identify any adverse events
To determine nutritional status
To determine the costs to the NHS

Secondary ID(s)

917741

Source(s) of Monetary Support

NIHR (HTA, 14/22/23)