Understanding Inflammation, InFection and Interventions in Severe Exacerbations of Cystic Fibrosis (UNIFIED-CF)

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.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis (CF); Cystic Fibrosis Pulmonary Exacerbation

Detailed Description

Participants will be recruited by staff within the care of UK CF centres. Initial discussions will occur either during routine outpatient reviews, telephone consultations or during admissions. Consent will take place prior to any other procedures. The investigators will provide the option of re-using baseline stable visits from the CF-Tracker study as stable visits for the UNIFIED-CF study. Consent to do this is specifically taken in UNIFIED, the investigators have added this as an option, and participants can opt to repeat the visit.

Participants will be people living with cystic fibrosis being cared for at a participating centre in the UK. The study will enrol only those who are considered to be at risk for severe exacerbation in the next 24 months. 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. Participants taking part in another hub study (CF-Tracker, IRAS: 338539) where the same data and samples are being collected will not need to repeat this visit and will be given the option of re-using the outcomes from the previous visit, or participants can also opt to repeat the visit.

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 arm of the UNIFIED study and will be monitored during their admission for up to a maximum of 17 days. In this arm, participants will undergo repeated assessments at pre-specified timepoints before and during their treatment at Pre-IV antibiotic baseline, Day 3 (range = day 2-4), Day 7 (range = day 6-8), Day 10 (range = day 9-12) and discharge day, alongside standard clinical care. A follow-up visit will take place after 6-14 weeks once the participant has returned to clinical stability. After this follow-up visit their will be no further participation.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Alexander Horsley, MA MBChB MRCP PhD FERS; Phone Number: 01612915869; Email: Alexander.horsley@manchester.ac.uk
• Study Contact Backup: Name: Cheuk Ning Sharon Chau; Phone Number: 01613060797; Email: cheukningsharon.chau@manchester.ac.uk

Study Locations

• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Not yet recruiting
    • Cardiff and Vale University Health Board
    • Contact: Jamie Duckers, MB BCH (Hons), MD; Phone Number: 02920 715382; Email: Jamie.duckers@wales.nhs.uk
    • Contact: Katherine Cabasan-Rose; Phone Number: 02920 715510; Email: katherine.cabasan-rose@wales.nhs.uk
    • Principal Investigator: Jamie Duckers, MB BCH (Hons), MD
  • Exeter, United Kingdom, EX2 5DW
    • Not yet recruiting
    • Royal Devon and Exeter Hospital (Wonford)
    • Contact: Phillip Mitchelmore; Phone Number: 01392 40 6981; Email: philip.mitchelmore@nhs.net
    • Contact: Sophie Whiteley; Phone Number: 01392 40 6981; Email: s.whiteley1@nhs.net
    • Principal Investigator: Phillip Mitchelmore
  • Leeds, United Kingdom, LS9 7TF
    • Not yet recruiting
    • Leeds Adult CF Centre
    • Contact: Daniel Peckham, MBBS MRCP DM FRCP; Phone Number: 07850070551; Email: d.g.peckham@leeds.ac.uk
    • Contact: Helen Chadwick; Email: helen.chadwick4@nhs.net
    • Principal Investigator: Daniel Peckham, MBBS MRCP DM FRCP
  • Liverpool, United Kingdom, L14 3PE
    • Not yet recruiting
    • Liverpool Heart & Chest Hospital
    • Contact: Fredrick Frost, BMedSci, BMBS, MRCP(UK), MD; Phone Number: 0151 254 3427; Email: freddy.frost@lhch.nhs.uk
    • Principal Investigator: Fredrick Frost, BMedSci, BMBS, MRCP(UK), MD
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • Manchester Adult Cystic Fibrosis Centre
    • Contact: Alexander Horsley, MA MBChB MRCP PhD FERS; Phone Number: 0161 2912046; Email: alexander.horsley@manchester.ac.uk
    • Contact: Natalie Hill; Phone Number: 07488 372 221; Email: Natalie.Hill@mft.nhs.uk
    • Principal Investigator: Peter Barry
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Not yet recruiting
    • Newcastle Adult CF Centre
    • Principal Investigator: Simon Doe
    • Contact: Simon Doe; Phone Number: 0191 2824877; Email: Simon.doe@nhs.net
    • Contact: Alan Anderson; Email: alan.anderson8@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

United Kingdom

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Alexander Horsley

Publications and helpful links

Helpful Links

• Hub website, with study pages

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: 338540

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Once collected and full anonymised, data will be made open to share based on "FAIR" data principles. Access to emerging datasets, or parts of datasets, is also possible based on a Data Access Application to the study team, which will be reviewed by the steering committee.
• IPD Sharing Time Frame: Details to be decided, but plan would be to make complete datasets open access.
• IPD Sharing Access Criteria: Data access is by application to the Steering Committee. For details on how to apply please email the study coordinator or PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No