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

NCT07484607 | Recruiting

• 1 other identifier: 338540
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 6

Brief Summary

The UNIFIED-CF study is an observational study designed to investigate the impacts of treatment given for severe pulmonary exacerbations in people living with cystic fibrosis (pwCF). Exacerbations are episodes when pwCF become more unwell, typically characterised by increased cough, sputum, and breathlessness and treated with a combination of oral and/or intravenous antibiotics. Severe exacerbations require treatment with intravenous antibiotics and impart considerable morbidity on pwCF. In this study, the investigators will recruit people at risk of severe CF exacerbations when they are well and if/when they are subsequently admitted for treatment of an exacerbation, the investigators will track symptoms and lung function during recovery, and collect blood, sputum and stool samples to allow us to explore the biological mechanisms of exacerbations and how they relate to different treatment responses. The study is event driven and will complete recruitment once 125 participants have completed treatment and follow-up for a severe exacerbation event. This study is funded by the Cystic Fibrosis Trust. This study is part of a wider programme of research, led by the PULSE-CF Innovation Hub (and hosted by the University of Manchester). The aim of the Hub is that the data from the UNIFIED-CF study will ultimately support the design of a platform clinical trial to test exacerbation-prevention interventions in CF.

Conditions

Cystic Fibrosis (CF); Cystic Fibrosis Pulmonary Exacerbation

Outcome Measures

Primary Outcomes (1)

• Response to standard-of-care antibiotic treatment

  Response (early responders, responders or non-responders) to standard-of-care antibiotic treatment in terms of symptomatic, lung function and biomarker recovery.

  7 days

Study Arms (1)

Single Group

Up to 300 participants will be recruited across 6 sites (expected number needed to get 125 exacerbations = 200). Participants will be assessed during a period of clinical stability. Clinical data, including lung function (spirometry), venous blood draw, sputum and urine sample and demographic data will be collected. If a participant has had a stable baseline visit but has not undergone any eligible CF exacerbations, they will be monitored for two years. They will be invited to a second stable baseline visit to repeat the same measurements after 12 months (range 10-14 months). If participants are admitted to one of the participating CF units for treatment of a pulmonary exacerbation, they will be eligible to take part in the Exacerbation Treatment. Clinical samples, including lung function (spirometry), impulse oscillometry, FeNO, exhaled VOC, nasal liquid, venous blood draw, sputum and urine sample will be collected at pre-specified timepoints before and during their treatment.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

United Kingdom

You may qualify if:

• 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.
• Receiving care from a UK Adult Cystic Fibrosis Centre taking part in the study.
• EITHER:
• Have had at least 1 previous exacerbation of CF lung disease, treated with intravenous antibiotics, in the previous 12 months.
• Enrolled in the CF-Tracker study (IRAS ID 338539) within the last 24 months (dated from date of completion of baseline Tracker visit)
• 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.
• Able to produce sputum (spontaneous or induced) at baseline visit.
• Able to understand the patient information sheet, willing to consent to study protocol.

You may not qualify if:

• 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.
• Extensive antibiotic allergies or intolerances that mean they could not be treated with standard CF antibiotic regimens, as outlined in section 5.6.
• Subjects with infection with Mycobacteria tuberculosis
• 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.
• Subjects receiving long term oral steroids at an equivalent dose of 10mg or more per day of prednisolone.
• Subjects receiving any other form of long term immune-suppressant therapy.
• 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.
• Planning on participating in a clinical trial of a novel experimental investigational medical product in the next 12 months.

Sponsors & Collaborators

• Alexander Horsley: lead

Study Sites (6)

Cardiff and Vale University Health Board

Cardiff, CF14 4XW, United Kingdom

NOT YET RECRUITING

Royal Devon and Exeter Hospital (Wonford)

Exeter, EX2 5DW, United Kingdom

NOT YET RECRUITING

Leeds Adult CF Centre

Leeds, LS9 7TF, United Kingdom

NOT YET RECRUITING

Liverpool Heart & Chest Hospital

Liverpool, L14 3PE, United Kingdom

NOT YET RECRUITING

Manchester Adult Cystic Fibrosis Centre

Manchester, M23 9LT, United Kingdom

RECRUITING

Newcastle Adult CF Centre

Newcastle upon Tyne, NE1 4LP, United Kingdom

NOT YET RECRUITING

Related Links

• Hub website, with study pages

Biospecimen

Retention: SAMPLES WITH DNA

* Spirometry - Impulse oscillometry - Venous blood draw * Sputum sample - Urine Sample - Nose and throat swab - Exhaled volatiles (VOCs) - Exhaled nitric oxide (FeNO) - Nasal liquid sample - Rectal swabs

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Central Study Contacts

Alexander Horsley, MA MBChB MRCP PhD FERS

CONTACT

01612915869; Alexander.horsley@manchester.ac.uk

Cheuk Ning Sharon Chau

CONTACT

01613060797; cheukningsharon.chau@manchester.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Respiratory Medicine and Honorary Consultant

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 20, 2026
• Study Start: October 9, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 24, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Details to be decided, but plan would be to make complete datasets open access.
• Access Criteria: Data access is by application to the Steering Committee. For details on how to apply please email the study coordinator or PI

Locations

GB (6)