Inflammation, infection and treatments during severe cystic fibrosis flare-ups

Understanding Inflammation, InFection and Interventions in Severe Exacerbations of Cystic Fibrosis

Researchers will follow people with cystic fibrosis who are at risk of severe lung flare-ups to see if symptoms, lung tests, and biological samples explain different responses to intravenous antibiotics.

Quick facts

• Study type: Observational
• Enrollment: 200 (estimated)
• Ages: 16 Years and up
• Sex: All
• Sponsor: University of Manchester (Academic / other)
• Locations: 6 sites (Cardiff and 5 other locations)
• Trial ID: NCT07484607 on ClinicalTrials.gov

What this trial studies

UNIFIED-CF recruits adults with confirmed cystic fibrosis at participating UK centres while they are clinically stable and follows them for up to two years to capture severe pulmonary exacerbations treated with intravenous antibiotics. When a qualifying exacerbation occurs, investigators record symptoms and lung function during recovery and collect blood, sputum and stool samples. The study is event-driven and aims to complete recruitment once 125 exacerbations have been captured, enrolling up to 300 participants across several UK sites and allowing reuse of baseline data from the CF-Tracker project where available. Collected clinical and biological data will be compared across different antibiotic regimens to explore mechanisms linked to treatment response.

Who should consider this trial

Good fit: Adults with confirmed cystic fibrosis under care at a participating UK adult CF centre who can produce sputum and have had an IV-treated exacerbation in the past 12 months or are enrolled in CF-Tracker are ideal candidates.

Not a fit: People not followed at participating centres, unlikely to require IV antibiotics, unable to produce sputum, or treated with antibiotic regimens outside the study's planned treatments may not receive direct benefit.

Why it matters

Potential benefit: If successful, the results could help tailor antibiotic and supportive care for severe CF exacerbations and reduce recovery time and complications.

How similar studies have performed: Other observational cohorts, including CF-Tracker, have collected paired stable and exacerbation samples and produced insights into exacerbation biology, but this event-driven multi-site collection of blood, sputum and stool adds additional depth.

Eligibility criteria

Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis (CF), defined as presence of two pathogenic CF-causing CFTR mutations AND clinical features consistent with a diagnosis of CF, OR presence of at least one pathogenic CF-causing CFTR mutation AND sweat chloride (before use of CFTR modulators) \>60mmol/L AND clinical features consistent with a diagnosis of CF.
2. Receiving care from a UK Adult Cystic Fibrosis Centre taking part in the study.
3. EITHER:

   • Have had at least 1 previous exacerbation of CF lung disease, treated with intravenous antibiotics, in the previous 12 months.

   OR

   • Enrolled in the CF-Tracker study (IRAS ID 338539) within the last 24 months (dated from date of completion of baseline Tracker visit)
4. In case of treatment for an exacerbation, likely to be treated with a ß-lactam or an anti-pseudomonal penicillin, combined with tobramycin or colistin, per CF Trust and NICE guidelines for 1st-line CF therapies.
5. Able to produce sputum (spontaneous or induced) at baseline visit.
6. Able to understand the patient information sheet, willing to consent to study protocol.

Exclusion Criteria:

1. When attending for the baseline visit participants should be clinically stable at the time of the visit. This is defined as no acute change in their baseline symptoms or presence of new viral symptoms. They should not be on additional antibiotics or anti-viral therapies for any reason (above their usual medications), and should have completed any such additional therapies at least 4 weeks prior.
2. Extensive antibiotic allergies or intolerances that mean they could not be treated with standard CF antibiotic regimens, as outlined in section 5.6.
3. Subjects with infection with Mycobacteria tuberculosis
4. Subjects with active ABPA, defined as receiving treatment for ABPA currently or within the last 4 months, or those considered at risk of requiring treatment for ABPA in the next 12 months.
5. Subjects receiving long term oral steroids at an equivalent dose of 10mg or more per day of prednisolone.
6. Subjects receiving any other form of long term immune-suppressant therapy.
7. Subjects with non-tuberculous mycobacteria (NTM) infection who are undergoing active eradication therapy. Subjects with chronic NTM infection who are not on eradication therapy, and not expecting to start this within the next 12 months, are not excluded.
8. Any other condition, co-morbidity or other feature that, in the opinion of the investigator would render the subject unable to complete the protocol or unsuitable for inclusion.
9. Planning on participating in a clinical trial of a novel experimental investigational medical product in the next 12 months.

Where this trial is running

Cardiff and 5 other locations

• Cardiff and Vale University Health Board — Cardiff, United Kingdom (Not_yet_recruiting)
• Royal Devon and Exeter Hospital (Wonford) — Exeter, United Kingdom (Not_yet_recruiting)
• Leeds Adult CF Centre — Leeds, United Kingdom (Not_yet_recruiting)
• Liverpool Heart & Chest Hospital — Liverpool, United Kingdom (Not_yet_recruiting)
• Manchester Adult Cystic Fibrosis Centre — Manchester, United Kingdom (Recruiting)
• Newcastle Adult CF Centre — Newcastle upon Tyne, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Alexander Horsley, MA MBChB MRCP PhD FERS

Conditions Cystic Fibrosis; Cystic Fibrosis Pulmonary Exacerbation